John Garner's Technical Blog
John GarnerJohn Garner, Manager

What's New and on the Manager's Mind

A blog dedicated to answering technical questions in an open format relating to products from PolySciTech, a division of Akina, Inc.


Select a topic to hide all other entries.
The most recent item is at the top.

Mal-PEG-PLGA and mPEG-PLGA from PolySciTech used in development of nanoparticle-based Parkinson’s treatment

Wednesday, January 17, 2018, 9:09 PM ET

Parkinson’s disease is a wide-spread neurodegenerative disorder with over 200,000 USA cases per year. The primary symptoms are loss of control over muscle movements which get progressively worse with time. This disease is caused by damage to dopaminergic neurons which leads to a lack of dopamine in the brain. Although incurable, there are drugs that can delay the progression of Parkinson’s. Because the drug action must occur within the brain, any medicine applied must cross the blood-brain-barrier, a screen that prevents most medicines from reaching the brain. Recently, researchers at Yantai University and Shandong Luye Pharmaceutics utilized mal-PEG-PLGA (Polyvivo AI109) and mPEG-PLGA (PolyVivo AK104) from PolySciTech (www.polyscitech.com) to generate lactoferin-decorated nanoparticles for rotigotine delivery across the blood-brain-barrier as a potential treatment for Parkinson’s disease. This research holds promise to halt the progress of this lethal disease. Read more: Yan X, Xu L, Bi C, Duan D, Chu L, Yu X, Wu Z, Wang A, Sun K “Lactoferrin-modified rotigotine nanoparticles for enhanced nose-to-brain delivery: LESA-MS/MS-based drug biodistribution, pharmacodynamics, and neuroprotective effects” International Journal of Nanomedicine, 9 January 2018 Volume 2018:13 Pages 273—281 https://www.dovepress.com/lactoferrin-modified-rotigotine-nanoparticles-for-enhanced-nose-to-bra-peer-reviewed-fulltext-article-IJN

“Introduction: Efficient delivery of rotigotine into the brain is crucial for obtaining maximum therapeutic efficacy for Parkinson’s disease (PD). Therefore, in the present study, we prepared lactoferrin-modified rotigotine nanoparticles (Lf-R-NPs) and studied their biodistribution, pharmacodynamics, and neuroprotective effects following nose-to-brain delivery in the rat 6-hydroxydopamine model of PD. Materials and methods: The biodistribution of rotigotine nanoparticles (R-NPs) and Lf-R-NPs after intranasal administration was assessed by liquid extraction surface analysis coupled with tandem mass spectrometry. Contralateral rotations were quantified to evaluate pharmacodynamics. Tyrosine hydroxylase and dopamine transporter immunohistochemistry were performed to compare the neuroprotective effects of levodopa, R-NPs, and Lf-R-NPs. Results: Liquid extraction surface analysis coupled with tandem mass spectrometry analysis, used to examine rotigotine biodistribution, showed that Lf-R-NPs more efficiently supplied rotigotine to the brain (with a greater sustained amount of the drug delivered to this organ, and with more effective targeting to the striatum) than R-NPs. The pharmacodynamic study revealed a significant difference (P<0 .05="" 6-hydroxydopamine-induced="" alleviated="" and="" between="" biodistribution="" brain="" conclusion:="" contralateral="" deliver="" disease="" dopaminergic="" drug="" effects="" efficacy.="" efficiently="" enhancing="" findings="" for="" furthermore="" have="" in="" keywords:="" lactoferrin-modified="" lf-r-nps="" might="" model="" more="" nanoparticles="" neurodegeneration="" neuroprotective="" nigrostriatal="" nose="" o:p="" of="" our="" parkinson="" pd.="" pharmacodynamics="" potential="" r-nps.="" rat="" rats="" rotations="" rotigotine="" s="" show="" significantly="" that="" the="" therapeutic="" thereby="" therefore="" those="" to="" treated="" treatment="" with="">

PLGA-PEG-Mal from PolySciTech used in development of immunosuppressant releasing tissue scaffold

Monday, January 1, 2018, 9:28 PM ET

One of the major challenges in stem-cell and tissue engineering is rejection of the new cells by the body through the immune system. Since systemic delivery of immunosuppressant medicines has severe side-effects, a better solution is localized delivery of immunosuppressants to prevent the cells in the scaffold from being attacked by immune cells. Recently, researchers from Fudan University, Tianjin Medical University (China), and Ewha Women’s University (Korea) used PLGA-PEG-Mal (PolyVivo AI136) from PolySciTech (www.polyscitech.com) to create tacrolimus loaded PLGA-PEG- RADA16 self-attractive nanoparticles. These were loaded into stem-cell hydrogels and remained within the hydrogel by electrostatic attraction. This resulted in a consistent and controlled release of immunosuppressant from the scaffold to prevent immune response against the loaded stem cells. This research holds promise to improve results for a wide array of tissue engineering applications. Read more: Li, Ruixiang, Jianming Liang, Yuwei He, Jing Qin, Huining He, Seungjin Lee, Zhiqing Pang, and Jianxin Wang. "Sustained Release of Immunosuppressant by Nanoparticle-anchoring Hydrogel Scaffold Improved the Survival of Transplanted Stem Cells and Tissue Regeneration." Theranostics 2018; 8(4): 878-893. doi: 10.7150/thno.22072 http://www.thno.org/v08p0878.pdf

“The outcome of scaffold-based stem cell transplantation remains unsatisfied due to the poor survival of transplanted cells. One of the major hurdles associated with the stem cell survival is the immune rejection, which can be effectively reduced by the use of immunosuppressant. However, ideal localized and sustained release of immunosuppressant is difficult to be realized, because it is arduous to hold the drug delivery system within scaffold for a long period of time. In the present study, the sustained release of immunosuppressant for the purpose of improving the survival of stem cells was successfully realized by a nanoparticle-anchoring hydrogel scaffold we developed. Methods: Poly (lactic-co-glycolic acid) (PLGA) nanoparticles were modified with RADA16 (RNPs), a self-assembling peptide, and then anchored to a RADA16 hydrogel (RNPs + Gel). The immobilization of RNPs in hydrogel was measured in vitro and in vivo, including the Brownian motion and cumulative leakage of RNPs and the in vivo retention of injected RNPs with hydrogel. Tacrolimus, as a typical immunosuppressant, was encapsulated in RNPs (T-RNPs) that were anchored to the hydrogel and its release behavior were studied. Endothelial progenitor cells (EPCs), as model stem cells, were cultured in the T-RNPs-anchoring hydrogel to test the immune-suppressing effect. The cytotoxicity of the scaffold against EPCs was also measured compared with free tacrolimus-loaded hydrogel. The therapeutic efficacy of the scaffold laden with EPCs on the hind limb ischemia was further evaluated in mice. Results: The Brownian motion and cumulative leakage of RNPs were significantly decreased compared with the un-modified nanoparticles (NPs). The in vivo retention of injected RNPs with hydrogel was obviously longer than that of NPs with hydrogel. The release of tacrolimus from T-RNPs + Gel could be sustained for 28 days. Compared with free tacrolimus-loaded hydrogel, the immune responses were significantly reduced and the survival of EPCs was greatly improved both in vitro and in vivo. The results of histological evaluation, including accumulation of immune cells and deposition of anti-graft antibodies, further revealed significantly lessened immune rejection in T-RNPs-anchoring hydrogel group compared with other groups. In pharmacodynamics study, the scaffold laden with EPCs was applied to treat hind limb ischemia in mice and significantly promoted the blood perfusion (~91 % versus ~36 % in control group). Conclusion: The nanoparticle-anchoring hydrogel scaffold is promising for localized immunosuppressant release, thereby can enhance the survival of transplanted cells and finally lead to successful tissue regeneration. Key words: stem cell; immune suppression; tacrolimus; nanoparticles; endothelial progenitor cells; RADA16 hydrogel.”

Searchable publication listings by product and application available on Akina website

Friday, December 22, 2017, 3:42 PM ET

The number of peer-reviewed journal publications using PST products per year has been steadily increasing over the past several years. This has led to a berth of valuable data regarding the polymer applications and uses. Since this is useful technical data for these products, as much as possible, we try to keep our website up to date with all publications using our products to provide our customers with this valuable resource. If you are interested in PST products for your research and want to get some ideas about how they have been used by others, make sure to visit https://akinainc.com/polyscitech/products/polyvivo/referenced_by.phpfor a full listing of publications. We also have metadata uploaded with keywords and abstracts, so keyword searching can give more details regarding specific applications. Alternatively, if you have used PST materials in a publication and you don’t see it listed, contact jg@akinainc.com with the citation to get it added.

As a side note, this is the last blog posting before Akina closes for 2017. Please note: Akina, Inc. will be closed December 25th through January 2nd for the Christmas and New Year's holidays. Orders placed during this time will be processed when we re-open on Wednesday, January 3rd. Happy Holidays to all.

mPEG-PLA from PolySciTech used in development of nanoparticle treatment to protect brain tissue from inflammation damage

Thursday, December 21, 2017, 4:49 PM ET

One of the major contributing factors to morbidity and death from brain cancer and other neurodegenerative disorders is the inflammation brought on within the brain tissue itself. This leads to swelling, oxidation, and potentially death. Typically treating any ailment that affects the brain is difficult as relatively few medicinal compounds cross from the blood stream into the brain tissue (the blood-brain-barrier). Nanotechnology can be used to improve this however. Recently, researchers at Kent State University and Northeast Ohio Medical University used mPEG-P(DL)La (PolyVivo AK021) from PolySciTech (www.polyscitech.com) to generate a delivery system for simvastatin to protect against neuroinflammation. This research holds promise to reduce damage caused by brain-tumors as well as other diseases implicated with inflammation of neural tissue. Read more: Manickavasagam, Dharani, Kimberly Novak, and Moses O. Oyewumi. "Therapeutic Delivery of Simvastatin Loaded in PLA-PEG Polymersomes Resulted in Amplification of Anti-inflammatory Effects in Activated Microglia." The AAPS Journal 20, no. 1 (2018): 18. https://link.springer.com/article/10.1208/s12248-017-0176-3

“Abstract: Simvastatin (Sim), a lipid-lowering drug has been studied in chronic neuroinflammation associated with degenerative brain disorders due to its potential protective properties against inflammatory reaction, oxidative damage, neuronal dysfunction, and death. Meanwhile, potential application of Sim in neuroinflammation will require a suitable delivery system that can overcome notable challenges pertaining to poor blood–brain barrier (BBB) permeability and side/off-target effects. Herein, we engineered and characterized nano-sized polymersomes loaded with Sim (Sim-Ps) using PEG-PdLLA (methoxy polyethylene glycol-poly(d,l) lactic acid) diblock co-polymers. Studies in BV2 microglia indicated that Sim-Ps was superior to Sim alone in suppressing nitric oxide (NO) and proinflammatory cytokines (interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) secretion against LPS activation. The effectiveness of Sim-Ps as compared with Sim alone, in attenuating NO and cytokine production by activated BV2 cells can be attributed to (a) colloidal stability of the delivery platform, (b) protracted release of biologically active Sim, and (c) particulate internalization coupled with enhanced Sim exposure to BV2 cells. Intranasal delivery in BALB/c mice demonstrated enhanced brain distribution with increasing time after administration. Overall data demonstrated suitability of PEG-PdLLA polymersomes in Sim delivery for potential application in treating neuroinflammation. Key Words: inflammation, microglia, neuroprotection, polymersomes, simvastatin”

mPEG-PLA from PolySciTech investigated for use as an ultrasound contrast-agent

Thursday, December 21, 2017, 4:48 PM ET

Ultrasound imaging is widely used as a diagnostic tool in medicine, but suffers from the drawback of relatively poor contrast. For this reason, this technique is often used after injection of a specific contrast agent, such as microbubbles or liposomes containing mannitol, to provide for improved imaging of features within the tissue. Recently, researchers from The George Washington University and North Dakota State University utilized mPEG-PLLA (Polyvivo AK004) from PolySciTech (www.polyscitech.com) to generate acoustic polymersomes as a contrast agent and investigated their acoustic properties. This research holds promise for improving the diagnostic capabilities of ultrasound. Read more: Xia, Lang, Fataneh Karandish, Krishna Nandan Kumar, James Froberg, Prajakta Kulkarni, Kara N. Gange, Yongki Choi, Sanku Mallik, and Kausik Sarkar. "Acoustic Characterization of Echogenic Polymersomes Prepared From Amphiphilic Block Copolymers." Ultrasound in medicine & biology (2017). https://www.sciencedirect.com/science/article/pii/S0301562917324092

“Abstract: Polymersomes are a class of artificial vesicles prepared from amphiphilic polymers. Like lipid vesicles (liposomes), they too can encapsulate hydrophilic and hydrophobic drug molecules in the aqueous core and the hydrophobic bilayer respectively, but are more stable than liposomes. Although echogenic liposomes have been widely investigated for simultaneous ultrasound imaging and controlled drug delivery, the potential of the polymersomes remains unexplored. We prepared two different echogenic polymersomes from the amphiphilic copolymers polyethylene glycol–poly-DL-lactic acid (PEG-PLA) and polyethylene glycol–poly-L-lactic acid (PEG-PLLA), incorporating multiple freeze-dry cycles in the synthesis protocol to ensure their echogenicity. We investigated acoustic behavior with potential applications in biomedical imaging. We characterized the polymeric vesicles acoustically with three different excitation frequencies of 2.25, 5 and 10 MHz at 500 kPa. The polymersomes exhibited strong echogenicity at all three excitation frequencies (about 50- and 25-dB enhancements in fundamental and subharmonic, respectively, at 5-MHz excitation from 20 µg/mL polymers in solution). Unlike echogenic liposomes, they emitted strong subharmonic responses. The scattering results indicated their potential as contrast agents, which was also confirmed by clinical ultrasound imaging. Key Words: Ultrasound imaging; Contrast agent; Microbubble; Polymersomes; Echogenic; Drug delivery”

mPEG-PLGA from PolySciTech used in development of microparticle-based delivery system for regulatory T-cell induction factors as an anti-inflammatory therapy

Tuesday, December 19, 2017, 8:59 AM ET

Several diseases and conditions are associated with an excessive immune response which leads to inflammation that can damage tissue. There are medicines available which can reduce the immune response (e.g. anti-histamines, steroidal anti-inflammatories) however, these all have side-effects due to their relatively non-specific nature in globally preventing immune response. The immune system itself has a built-in regulatory mechanism which acts through regulatory T-cells that act to reduce immune response and improve the recognition of antigens as ‘self.’ A more effective and therapeutic strategy is to provide factors which promote the formation and recruitment of regulatory t-cells to a site of inflammation. Recently, researchers at The University of Pittsburgh used mPEG-PLGA (PolyVivo AK037) from PolySciTech (www.polyscitech.com) to create a microparticle designed to release pro-regulatory-t-cell factors into the eye as a means to reduce localized inflammation by promoting the body’s own feedback system to control the immune response. This research holds promise not only to treat ocular diseases, but to be applied to other disease in which excessive immune response is implicated. Read more: Ratay, Michelle L., Stephen C. Balmert, Abhinav P. Acharya, Ashlee C. Greene, Thiagarajan Meyyappan, and Steven R. Little. "TRI Microspheres prevent key signs of dry eye disease in a murine, inflammatory model." Scientific Reports 7, no. 1 (2017): 17527. https://www.nature.com/articles/s41598-017-17869-y

“Abstract: Dry eye disease (DED) is a highly prevalent, ocular disorder characterized by an abnormal tear film and ocular surface. Recent experimental data has suggested that the underlying pathology of DED involves inflammation of the lacrimal functional unit (LFU), comprising the cornea, conjunctiva, lacrimal gland and interconnecting innervation. This inflammation of the LFU ultimately results in tissue deterioration and the symptoms of DED. Moreover, an increase of pathogenic lymphocyte infiltration and the secretion of pro-inflammatory cytokines are involved in the propagation of DED-associated inflammation. Studies have demonstrated that the adoptive transfer of regulatory T cells (Tregs) can mediate the inflammation caused by pathogenic lymphocytes. Thus, as an approach to treating the inflammation associated with DED, we hypothesized that it was possible to enrich the body’s own endogenous Tregs by locally delivering a specific combination of Treg inducing factors through degradable polymer microspheres (TRI microspheres; TGF-β1, Rapamycin (Rapa), and IL-2). This local controlled release system is capable of shifting the balance of Treg/T effectors and, in turn, preventing key signs of dry eye disease such as aqueous tear secretion, conjunctival goblet cells, epithelial corneal integrity, and reduce the pro-inflammatory cytokine milieu in the tissue.”

PLA-Fluorescein from PolySciTech used in PhD thesis work on development of theranostic nanoparticles for treatment of heart-disease

Monday, December 18, 2017, 2:14 PM ET

A critical yet often overlooked factor in atherosclerosis (heart-disease) is inflammation, as swelling contributes to the constriction of the blood vessels and damage to the tissue. This also presents a potential therapeutic target as preventing inflammation can assist with reducing the incidence of morbidity and mortality with this disease. Recently, researchers at Massachusetts Institute of Technology used P(DL)La and P(DL)La-Fluorescein (PolyVivo AV016) from PolySciTech (www.polyscitech.com) to develop nanoparticles to deliver simvastatin to affected tissue. The use of fluorescein conjugated PLA allowed for easy tracking of the nanoparticles by visual techniques. This research holds promise to treat inflammatory diseases. Read more: Chung, Bomy Lee. "Theranostic nanoparticles for the management of inflammatory diseases and conditions." PhD diss., Massachusetts Institute of Technology, 2017. https://dspace.mit.edu/handle/1721.1/112504

“Abstract: Atherosclerosis, the gradual buildup of plaques within arteries, is the main cause of cardiovascular diseases (CVDs). The World Health Organization reports that CVDs are the number one cause of death in the world. In the United States alone, around 85 million people suffer from CVDs; this is associated with a cost of over $316 billion per year and responsible for about a third of all deaths in the US. Recent findings have shown that inflammation plays a pivotal role in atherosclerosis. Although statins have traditionally been prescribed for their lipid-lowering benefits, studies have indicated that they can have other effects as well (so-called "pleiotropic effects"), including anti-inflammatory, anti-oxidant, and anti-thrombotic benefits. This thesis presents a novel theranostic (therapeutic + diagnostic) nanoparticle platform for the treatment and diagnosis of atherosclerosis. Given the anti-inflammatory effects of statins when cells are directly treated, the aim of this nanoparticle platform was to target macrophages within plaques given their central role in plaque development and progression. First, simvastatin-loaded nanoparticles were designed and optimized. The particles consisted of a biodegradable polymer core and a lipid shell. Using bulk nanoprecipitation methods, as well as microfluidic devices, the physical characteristics of the particles could be controlled and fine-tuned to meet the desired specifications: 100 to 200 nm in size, -15 to -20 mV in zeta potential, and 70%+ simvastatin loading efficiency. Imaging agents, such as iron oxide nanocrystals used for magnetic resonance imaging (MRI), were successfully incorporated into the nanoparticles and can offer diagnostic capabilities to the nanoparticles. Next, various nanoparticle formulations were shown to be therapeutically effective in cell and mice models of atherosclerosis. For instance, in vitro treatment of macrophages led to decreases in the expression of TNF-a and MCP-1 by roughly 20% and 50%, respectively. This pattern has also been observed in murine models, with researchers showing that simvastatin-loaded particles can halt plaque development (and even decrease plaque area) while reducing the expression of pro-inflammatory genes (e.g., of TNF-a, IL- IP) by an order of magnitude. Overall, this thesis presents a new and innovative nanoparticle platform that has the potential for the simultaneous treatment and diagnosis of atherosclerosis. Given their anti-inflammatory benefits, these nanoparticles have the potential to impact the treatment of not only atherosclerosis but also various other inflammatory conditions and diseases as well.”

PLGA from PolySciTech used in developing Bioadhesive hydrogels for tissue-engineering applications

Monday, December 18, 2017, 2:13 PM ET

As a general rule, it is very difficult to have a material which adheres well to biological tissues. Biological tissues are warm, wet, and typically covered with a coating of proteins which tend to reduce adhesion. This makes designing adhesives for them very difficult. For tissue engineering applications it is critical that whatever scaffold or patch is applied, remains well-adhered to the tissue for it to work. The adhesive must also be biocompatible. Interestingly, a solution for bioadhesion has presented itself in nature from barnacles/mussels, which secrete an incredibly adhesive biopolymer to hold onto rocks. Recently, researchers at University of Texas at Arlington, used PLGA (PolyVivo AP154) from PolySciTech (www.polyscitech.com) to create nanoparticles to improve the bioadhesion of barnacle/mussel-inspired alginate-dopa hydrogels. This research holds promise for improved tissue engineering patches and scaffolds to treat wounds and defects. Read more: Pandey, Nikhil, Amirhossein Hakamivala, Cancan Xu, Prashant Hariharan, Boris Radionov, Zhong Huang, Jun Liao et al. "Biodegradable Nanoparticles Enhanced Adhesiveness of MusselLike Hydrogels at Tissue Interface." Advanced healthcare materials (2017). http://onlinelibrary.wiley.com/doi/10.1002/adhm.201701069/full

“Abstract: Popular bioadhesives, such as fibrin, cyanoacrylate, and albumin–glutaraldehyde based materials, have been applied for clinical applications in wound healing, drug delivery, and bone and soft tissue engineering; however, their performances are limited by weak adhesion strength and rapid degradation. In this study a mussel-inspired, nanocomposite-based, biodegradable tissue adhesive is developed by blending poly(lactic-co-glycolic acid) (PLGA) or N-hydroxysuccinimide modified PLGA nanoparticles (PLGA-NHS) with mussel-inspired alginate–dopamine polymer (Alg-Dopa). Adhesive strength measurement of the nanocomposites on porcine skin–muscle constructs reveals that the incorporation of nanoparticles in Alg-Dopa significantly enhances the tissue adhesive strength compared to the mussel-inspired adhesive alone. The nanocomposite formed by PLGA-NHS nanoparticles shows higher lap shear strength of 33 ± 3 kPa, compared to that of Alg-Dopa hydrogel alone (14 ± 2 kPa). In addition, these nanocomposites are degradable and cytocompatible in vitro, and elicit in vivo minimal inflammatory responses in a rat model, suggesting clinical potential of these nanocomposites as bioadhesives.”

mPEG-PLGA from PolySciTech used in development of combination chemotherapy nanoparticles for treatment of lung cancer

Monday, December 18, 2017, 2:10 PM ET

Lung cancer is a prevalent and deadly disease contributing to about 222,500 new cases and 155,870 deaths per year in America alone. Lung cancer propagates itself through cancer stem-cells, cells within cancer which can differentiate into multiple cell types. Treating the cancer requires both eliminating the mature cancer cells and the stem-cells, so that the cancer cannot grow back. Recently, researchers at Xiangyang Central Hospital and Second Military Medical University (China) used mPEG-PLGA (PolyVivo AK101) from PolySciTech (www.polyscitech.com) to generate salinomycin and gefitinib loaded nanoparticles for lung cancer treatment. This research holds promise to develop more effective treatment strategies for this disease by eliminating both cancer cells and cancer stem cells. Read more: Zhang, Yu, Qi Zhang, Jing Sun, Huijie Liu, and Qingfeng Li. "The combination therapy of salinomycin and gefitinib using poly (D, L-lactic-co-glycolic acid)-poly (ethylene glycol) nanoparticles for targeting both lung cancer stem cells and cancer cells." OncoTargets and therapy 10 (2017): 5653. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5709995/

“Abstract: Purpose: Lung cancer (LC) is the leading cause of cancer death worldwide. Evidences suggest that both LC cancer stem cells (CSCs) and cancer cells are supposed to be eliminated to achieve superior treatment effect against LC. Salinomycin could eradiate CSCs in various types of cancers, and gefitinib is a first-line therapy in LC. The purpose of the present study was to develop salinomycin-loaded nanoparticles (salinomycin-NPs) combined with gefitinib-loaded nanoparticles (gefitinib-NPs) to eradicate both LC CSCs and cancer cells. Methods: Salinomycin and gefitinib were encapsulated separately by poly(d,l-lactic-co-glycolic acid)-poly(ethylene glycol) nanoparticles by the emulsion/solvent evaporation approach. The anti-LC activity of salinomycin-NPs and gefitinib-NPs was investigated. Results: Salinomycin-NPs and gefitinib-NPs are of ~140 nm in size, high drug encapsulation efficacy and sustained release of drugs. CD133+ LC CSCs showed the characteristics of CSCs, including significantly enhanced stem cell gene expression, tumorsphere formation ability, and tumorigenicity in mice. Both salinomycin and salinomycin-NPs are capable of selectively inhibiting LC CSCs, as reflected by their enhanced cytotoxic effects toward CD133+ LC CSCs and ability to reduce tumorsphere formation in LC cell lines, whereas gefitinib and gefitinib-NPs could significantly inhibit LC cells. Salinomycin-NPs and salinomycin could reduce the population of LC CSCs in the tumors in vivo. It is noteworthy that salinomycin-NPs combined with gefitinib-NPs inhibited the growth of tumors more efficiently compared with salinomycin combined with gefitinib or single salinomycin-NPs or gefitinib-NPs. Conclusion: Salinomycin-NPs combined with gefitinib-NPs represent a potential approach for LC by inhibiting both LC CSCs and cancer cells. Keywords: cancer stem cells, lung cancer, nanoparticles, salinomycin, gefitinib”

PLGA and PLGA-PEG-Mal from PolySciTech used in development of cancer immunotherapy

Friday, December 15, 2017, 10:09 PM ET

One of the more insidious facets of cancer is that, for a variety of biochemical reasons, most cancers do not elicit an immune response from the body. The human body’s immune system is well adept at thwarting foreign cells and pathogens and is very capable of destroying many cancer cells once activated. For this reason, there has been a great deal of research in ‘immunotherapy’ which is effectively a process of vaccinating the human body against cancer so that it recognizes and destroys cancer cells as though they were pathogens. This provides for a much more selective therapy overall as compared to conventional cytotoxic chemotherapies. Recently, researchers at Dana Faber, Harvard Medical School, MIT, Howard Hughes Medical Institute, and Koch Institute for Integrative Cancer Research utilized Mal-PEG-PLGA (Cat# AI053) and PLGA (Cat # AP041) from PolySciTech (www.polyscitech.com) to generate nanoparticles with reactive exteriors. These nanoparticles were conjugated to targeting ligands via Michael’s reaction between the maleimide units and thiol-bearing antibody fragments. The formed nanoparticles were found to target immune cells and deliver immunotherapy agents to them. This research holds promise for enhanced cancer therapy. Read more: Cartwright, A.N., Hartl, C.A., Park, C.G., Schmid, D., Irvine, D.J., Freeman, G.J., Maiarana, J., Wucherpfennig, K.W., Goldberg, M.S., Subedi, N. and Puerto, R.B., 2017. T cell-targeting nanoparticles focus delivery of immunotherapy to improve antitumor immunity. Nature communications, 8, p.1747. https://www.nature.com/articles/s41467-017-01830-8

“Abstract: Targeted delivery of compounds to particular cell subsets can enhance therapeutic index by concentrating their action on the cells of interest. Because attempts to target tumors directly have yielded limited benefit, we instead target endogenous immune cell subsets in the circulation that can migrate actively into tumors. We describe antibody-targeted nanoparticles that bind to CD8+ T cells in the blood, lymphoid tissues, and tumors of mice. PD-1+ T cells are successfully targeted in the circulation and tumor. The delivery of an inhibitor of TGFβ signaling to PD-1-expressing cells extends the survival of tumor-bearing mice, whereas free drugs have no effect at such doses. This modular platform also enables PD-1-targeted delivery of a TLR7/8 agonist to the tumor microenvironment, increasing the proportion of tumor-infiltrating CD8+ T cells and sensitizing tumors to subsequent anti-PD-1. Targeted delivery of immunotherapy to defined subsets of endogenous leukocytes may be superior to administration of free drugs.”

PLGA-PEG-PLGA from PolySciTech used in development of infantile hemangioma treatment

Monday, December 11, 2017, 10:40 AM ET

Infantile hemangioma is a non-cancerous tumor in which an excess of blood vessels grow in a particular area with excessive cell proliferation. Small, skin hemangioma’s manifest as benign birthmarks and do not typically require treatment. However, large hemangioma’s or hemangioma’s that affect organs (especially the liver) can be fatal and require treatment. Since these affect primarily infants, treatment must be performed carefully as side-effects and other complications can be readily encountered due to size and metabolic features in very small children. Recently, researchers from Henan Provincial People’s Hospital and Second Military Medical University utilized PLGA-PEG-PLGA (Polyvivo#: AK016) from PolySciTech (www.polyscitech.com) to formulate urea-loaded microspheres as a delivery system to treat hemangioma. This research holds promise for treating this potentially life-threatening infantile disease. Read more: Zhu, Xiaoshuang, Xiaonan Guo, Dakan Liu, Yubin Gong, Jin Sun, and Changxian Dong. "Significant inhibition of infantile hemangioma growth by sustained delivery of urea from liposomes-in-microspheres." Oncology Reports 39, no. 1 (2018): 109-118. https://www.spandidos-publications.com/or/39/1/109

“Abstract: Infantile hemangioma (IH) is a benign pediatric tumor, and rapid growth of IH can result in serious morbidity and even mortality. Only one drug Hemangeol™ (propranolol hydrochloride oral solution) has been approved for the treatment of IH, whereas patients suffer from its adverse effects and high frequency of administration. We have used urea, an organic compound and a normal body metabolite, in the treatment of IH for 20 years, and demonstrated that urea is an effective and well-tolerated treatment for IH. To reduce the daily administration of urea, we firstly utilized urea-loaded liposomes-in-microspheres (ULIM) as a novel topical controlled release system to realize the sustained release of urea. ULIM were fabricated from the encapsulation of urea-loaded liposomes in poly(lactic-co-glycolic acid)-b-poly(ethylene glycol)-b-poly(lactic-co-glycolic acid) microspheres. The characteristics, activity and mechanism against IH of ULIM were examined in vitro and in vivo. ULIM were of a desired particle size (~62.4 µm), drug encapsulation efficiency (~51.5%) and sustained drug release for 40 days. ULIM inhibited the proliferation of hemangioma endothelia cells (HemECs) and expression of vascular endothelial growth factor-A in HemECs. The therapeutic effect of ULIM in IH was better than propranolol, urea, urea-loaded liposomes and urea-loaded microspheres in vivo, as reflected by markedly decreased hemangioma weight, volume and microvessel density. None of the treated mice showed behavioral changes, severe sideeffects and weight loss. Our results suggest that use of ULIM is a potential and safe approach with which to locally and efficiently deliver urea to hemangioma, and is a promising alternative to propranolol in the treatment of IH.”

PEG-PLGA from PolySciTech used in development of gastric cancer treatment

Friday, December 8, 2017, 10:19 PM ET

Gastric cancer is a very common and deadly form of cancer which kills about 11,000 people per year in America. Eliminating cancer stem cells is a key step to treating this form of cancer. Recently, researchers working at Sichuan University, Guizhuo Provincial People’s Hospital, and Second Military Medical University (China) utilized PEG-PLGA From PolySciTech (www.polyscitech.com) to develop nanoparticles loaded with salinomycin, which kills cancer stem-cells, and docetaxel, a standard chemotherapy agent, for treatment of gastric cancer. They found this combination in nanoparticles suppressed tumor growth more effectively than alone or without the nanoparticles. This research holds promise for treating this common and lethal form of cancer. Read more: Li, Lan, Dejun Cui, Limin Ye, Yu Li, Liyi Zhu, Lanqun Yang, Banjun Bai, Zhao Nie, Jie Gao, and Yu Cao. "Codelivery of salinomycin and docetaxel using poly (D, L-lactic-co-glycolic acid)-poly (ethylene glycol) nanoparticles to target both gastric cancer cells and cancer stem cells." Anti-Cancer Drugs 28, no. 9 (2017): 989-1001. http://journals.lww.com/anti-cancerdrugs/Fulltext/2017/10000/Codelivery_of_salinomycin_and_docetaxel_using.6.aspx

“Cancer stem cells (CSCs) in gastric cancer (GC) have been established recently as key therapeutic targets for the successful treatment of GC. Emerging evidence suggests that both CSCs and cancer cells should be eradicated to achieve optimal therapeutic efficacy. In the present study, salinomycin, which has been reported to kill CSCs, was used in combination with docetaxel, a chemotherapeutic drug that is used as first-line therapy in GC, to eradicate both GC stem cells (SCs) and cancer cells. Salinomycin and docetaxel were loaded separately into poly(D,L-lactic-co-glycolic acid)-poly(ethylene glycol) nanoparticles of 140 nm with a narrow size distribution, high drug loading, and sustained drug release. GC SCs were isolated by magnetic-activated cell sorting on the basis of CD44 expression as the CSC phenotype. CD44+ GC SCs showed the characteristics of CSCs, including increased SC gene expression, tumorsphere formation capacity, and tumorigenicity in nude mice. We found that both salinomycin and salinomycin-loaded nanoparticles (salinomycin-NPs) could selectively eradicate GC SCs, as reflected by reduced tumorsphere formation capacity and the frequency of CD44+ GC cells, whereas docetaxel and docetaxel-loaded nanoparticles (docetaxel-NPs) could significantly eradicate GC cells. In nude mice bearing GC xenografts, salinomycin-NPs and salinomycin significantly decreased the intratumor population of GC SCs. Notably, salinomycin-NPs combined with docetaxel-NPs suppressed tumor growth more effectively than did salinomycin combined with docetaxel, single salinomycin-NPs, or docetaxel-NPs. Therefore, salinomycin-NPs combined with docetaxel-NPs represent a promising strategy for the treatment of GC by eradicating both GC SCs and cancer cells.”

Maleimide-PEG-PLGA from PolySciTech used in development of nanoparticle system for treatment of arthritis

Friday, December 8, 2017, 10:18 PM ET

Arthritis is a debilitating inflammatory disease of the joints which can damage cartilage and create a considerable amount of pain as well as loss of function for the patient. Targeted therapy offers hope for relief to patients from this chronic disease. One means of generating targeted nanoparticles is to utilize thiol-maleimide reaction to connect peptides to the exterior of Maleimide-reacting nanoparticles made using Mal-PEG-PLGA. Recently, Researchers at University of Connecticut and University of Harford utilized mPEG-PLGA (PolyVivo #AK037) and Maleimide-PEG-PLGA (Polyvivo #AI020) from PolySciTech (www.polyscitech.com) to generate a nanoparticle system for treatment of arthritis. This research holds promise for treating this debilitating disease. Read more: Jiang, Tao, Ho-Man Kan, Komal Rajpura, Erica J. Carbone, Yingcui Li, and Kevin W-H. Lo. "Development of Targeted Nanoscale Drug Delivery System for Osteoarthritic Cartilage Tissue." Journal of Nanoscience and Nanotechnology 18, no. 4 (2018): 2310-2317. http://www.ingentaconnect.com/contentone/asp/jnn/2018/00000018/00000004/art00006

Osteoarthritis is a severe and debilitating joint disease, which is characterized as results from damage and degeneration of the articular cartilage of the joint surfaces. The incidence of osteoarthritis is growing increasingly high while current treatment methods remain suboptimal. The major issue for current osteoarthritic medications is that patients frequently experience adverse, nonspecific side effects that are not a direct result of the specific pharmacological action of the drug. The treatment processes could be made more effective, safe, and comfortable if it were possible to deliver the drugs specifically to cartilage tissue. Therefore, developing site-specific and controlled drug release delivery systems is needed for overcoming the aforementioned issues. We have developed a poly(lactic-co-glycolic acid) (PLGA)-based nanoscale drug delivery system based on a short cartilage-targeting peptide sequence: WYRGRL. Nanoparticles (NPs) made of methoxy-poly(ethylene glycol) (PEG)-PLGA and maleimide-PEG-PLGA were prepared using a water-in-oil-in-water double emulsion and solvent evaporation method. Fluorescein isothiocyanate (FITC)-tagged WYRGRL peptide was then linked to the surface of the nanoparticles through the alkylation reaction between the sulfhydryl groups at the N-terminal of the peptide and the C═C double bond of maleimide at one end of the polymer chain to form thioether bonds. The conjugation of FITC-tagged WYRGRL peptide to PLGA NPs was confirmed by NMR technique. We further demonstrated that the novel delivery system binds very specifically to cartilage tissue in vitro and ex vivo. Given that biodegradable PLGA-based NPs have shown promise for drug delivery, they could be used for a positive advancement for treatments of osteoarthritic patients by creating a more effective treatment process that achieves healing results faster and with fewer deleterious side effects. Taken together, these promising results indicated that this nanoscale targeting drug delivery system was able to bind to cartilage tissue and might have a great potential for treating osteoarthritis. Keywords: Musculoskeletal Tissue; Nanomedicine; Osteoarthritis; Targeted Drug Delivery; Targeting Ligands

PEG-PLGA from PolySciTech used in development of nanoparticle-based Leukemia treatment

Friday, December 8, 2017, 10:17 PM ET

Leukemia is a cancer which affects how blood cells are produced in bone marrow and contributes to about 24,500 deaths each year in US. T cell acute lymphoblastic leukemia (T-ALL), in particular is a form of leukemia which has poor survival prognosis in adult (<50 a="" affected="" and="" be="" bone-marrow="" both="" by="" can="" chemotherapeutics.="" effect.="" effectiveness="" for="" from="" have="" href="http://www.polyscitech.com/" huazhong="" improved="" inhibitors="" into="" its="" jiao="" kinase="" maximum="" nanoparticles="" of="" other="" peg-plga="" polyscitech="" preferentially="" purchased="" recently="" regions="" requires="" researchers="" science="" shanghai="" technology="" the="" these="" tissue="" to="" tong="" traditional="" treatment="" treatments="" university="" uptake="" using="">www.polyscitech.com
) to make nanoparticles co-loaded with both IRAK (kinase inhibitor) and ABT-737 (microtubule-targeting chemotherapeutic) for leukemia therapy. This research holds promise to improve therapeutic and survival outcomes for this difficult to treat disease. Read more: Wu, Xiaoyan, Lin Wang, Yining Qiu, Bingyu Zhang, Zhenhua Hu, and Runming Jin. "Cooperation of IRAK1/4 inhibitor and ABT-737 in nanoparticles for synergistic therapy of T cell acute lymphoblastic leukemia." International Journal of Nanomedicine 12 (2017): 8025. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5673049/

“Abstract: T cell acute lymphoblastic leukemia (T-ALL) is caused by clonal expansion of variant T cell progenitors and is considered as a high risk leukemia. Contemporary single chemotherapy has a limited effect due to dynamic and versatile properties of T-ALL. Here IRAK1/4 inhibitor and ABT-737 were co-encapsulated into polyethylene glycol modified poly (lactic-co-glycolic acid) nanoparticles (IRAK/ABT-NP) to enhance synergistic therapy of T-ALL. The formulation was optimized to achieve high drug loading using Box-Behnken design and response surface methodology. The optimal parameter comprised 2.98% polymer in acetonitrile, a ratio of oil phase to water phase of 1:8.33, and 2.12% emulsifier concentration. High drug loading and uniform spherical shape was achieved. In vitro release study showed sustained release of IRAK1/4 inhibitor for 72 hours as well as sustained release of ABT-737 for more than 120 hours. Uptake efficiency of IRAK/ABT-NP and induced apoptotic T-ALL fraction by IRAK/ABT-NP were much higher than the IRAK1/4 and ABT-737 combined solution. IC50 of IRAK/ABT-NP was two-fold lower than free drug combination in Jurkat cells. Additionally, we conducted in vivo experiments in which IRAK/ABT-NP exhibited greater cytotoxicity toward T-ALL cells, the capacity to significantly restore white blood cell number in peripheral blood, and improved survival time of T-ALL mouse model compared to the IRAK1/4 and ABT-737 combined solution. Keywords: T cell acute lymphoblastic leukemia, IRAK1/4 inhibitor, ABT-737, Box-Behnken design and response surface methodology, PEG-PLGA”

PEG-PLA from PolySciTech utilized in development of nanoparticles to protect kidneys during transplant procedures.

Tuesday, December 5, 2017, 8:12 PM ET

Kidney transplantation is a life-saving practice in which a donor kidney is transplanted into a recipient. During kidney transplantation, damage to the organ can occur when the flow of blood through it stops (upon removal from the donor) and suddenly restarts again once placed in the recipient. This incidence of ‘reperfusion injury’ can damage the delicate lining of the organ and potentially lead to a loss of function. Recently, researchers from Yale University and University of Cambridge utilized mPEG-PLA (PolyVivo AK054) from PolySciTech (www.polyscitech.com) to develop nanoparticles that coat and protect the interior of kidneys so that they are less affected by reperfusion injury. This research holds promise both to protect organs for transplant, as well as to treat any problems with the organ during the time between removal and placement. Read more: Tietjen, Gregory T., Sarah A. Hosgood, Jenna DiRito, Jiajia Cui, Deeksha Deep, Eric Song, Jan R. Kraehling et al. "Nanoparticle targeting to the endothelium during normothermic machine perfusion of human kidneys." Science Translational Medicine 9, no. 418 (2017): eaam6764. http://stm.sciencemag.org/content/9/418/eaam6764.abstract

“Abstract: Particle perfusion for organ transplant: Ischemia-reperfusion injury, which occurs when a tissue or organ is temporarily cut off from blood flow, is a major issue limiting organ viability for transplantation. Tietjan et al. devised a way to target the injury-sensitive endothelium of organs during ex vivo perfusion. Using nanoparticles conjugated to an antibody targeting a protein expressed on endothelial cells, the authors demonstrated that they could perfuse human kidneys and that nanoparticles accumulated in kidney endothelial cells. In addition to expanding the pool of viable organs for transplant, this approach could potentially be used to deliver targeted therapies to organs during ex vivo perfusion rather than treating the transplant recipient systemically. Ex vivo normothermic machine perfusion (NMP) is a new clinical strategy to assess and resuscitate organs likely to be declined for transplantation, thereby increasing the number of viable organs available. Short periods of NMP provide a window of opportunity to deliver therapeutics directly to the organ and, in particular, to the vascular endothelial cells (ECs) that constitute the first point of contact with the recipient’s immune system. ECs are the primary targets of both ischemia-reperfusion injury and damage from preformed antidonor antibodies, and reduction of perioperative EC injury could have long-term benefits by reducing the intensity of the host’s alloimmune response. Using NMP to administer therapeutics directly to the graft avoids many of the limitations associated with systemic drug delivery. We have previously shown that polymeric nanoparticles (NPs) can serve as depots for long-term drug release, but ensuring robust NP accumulation within a target cell type (graft ECs in this case) remains a fundamental challenge of nanomedicine. We show that surface conjugation of an anti-CD31 antibody enhances targeting of NPs to graft ECs of human kidneys undergoing NMP. Using a two-color quantitative microscopy approach, we demonstrate that targeting can enhance EC accumulation by about 5- to 10-fold or higher in discrete regions of the renal vasculature. In addition, our studies reveal that NPs can also nonspecifically accumulate within obstructed regions of the vasculature that are poorly perfused. These quantitative preclinical human studies demonstrate the therapeutic potential for targeted nanomedicines delivered during ex vivo NMP.”

Cell-scaffold interaction quantitatively investigated using fluorescently labeled PLGA from PolySciTech

Tuesday, December 5, 2017, 8:06 PM ET

A powerful technique commonly applied in tissue engineering is cell-scaffolding in which a highly-porous, biocompatible material is implanted into a patient. This mesh allows for cells to grow inside of its structure to repair damaged or lost tissue. There still remains a great deal to learn about exactly how cells interact with the substrate they are growing on, as the structure and chemistry of the mesh is critical to how the cells grow. One common problem with growing roughly translucent microscopic cells on an opaque microfiber mesh is visualizing what is going on with the cells. This is where fluorescent imaging comes in to play. In this method, each component is bound to a specific dye that emits light when excited by a specific wavelength of light. This allows researchers to image each component of the system, separately. Recently, researchers from National institute of Standards and Technology (NIST) and National Institute of Health (NIH) utilized fluorescently conjugated PLGA-FKR648 (PolyVivo AV015) from PolySciTech (www.polyscitech.com) to make a series of cell-scaffolds and test their interactions with cells. The fluorescent nature of this polymer allowed for direct imaging of the mesh by fluorescence techniques, so they could investigate cell-interactions in fine detail. This research provides a valuable tool for tissue-engineering researchers looking to optimize their mesh designs. Read more: Bajcsy, Peter, Soweon Yoon, Stephen J. Florczyk, Nathan A. Hotaling, Mylene Simon, Piotr M. Szczypinski, Nicholas J. Schaub, Carl G. Simon, Mary Brady, and Ram D. Sriram. "Modeling, validation and verification of three-dimensional cell-scaffold contacts from terabyte-sized images." BMC Bioinformatics 18, no. 1 (2017): 526. https://bmcbioinformatics.biomedcentral.com/articles/10.1186/s12859-017-1928-x

“Background: Cell-scaffold contact measurements are derived from pairs of co-registered volumetric fluorescent confocal laser scanning microscopy (CLSM) images (z-stacks) of stained cells and three types of scaffolds (i.e., spun coat, large microfiber, and medium microfiber). Our analysis of the acquired terabyte-sized collection is motivated by the need to understand the nature of the shape dimensionality (1D vs 2D vs 3D) of cell-scaffold interactions relevant to tissue engineers that grow cells on biomaterial scaffolds. Results: We designed five statistical and three geometrical contact models, and then down-selected them to one from each category using a validation approach based on physically orthogonal measurements to CLSM. The two selected models were applied to 414 z-stacks with three scaffold types and all contact results were visually verified. A planar geometrical model for the spun coat scaffold type was validated from atomic force microscopy images by computing surface roughness of 52.35 nm ±31.76 nm which was 2 to 8 times smaller than the CLSM resolution. A cylindrical model for fiber scaffolds was validated from multi-view 2D scanning electron microscopy (SEM) images. The fiber scaffold segmentation error was assessed by comparing fiber diameters from SEM and CLSM to be between 0.46% to 3.8% of the SEM reference values. For contact verification, we constructed a web-based visual verification system with 414 pairs of images with cells and their segmentation results, and with 4968 movies with animated cell, scaffold, and contact overlays. Based on visual verification by three experts, we report the accuracy of cell segmentation to be 96.4% with 94.3% precision, and the accuracy of cell-scaffold contact for a statistical model to be 62.6% with 76.7% precision and for a geometrical model to be 93.5% with 87.6% precision. Conclusions: The novelty of our approach lies in (1) representing cell-scaffold contact sites with statistical intensity and geometrical shape models, (2) designing a methodology for validating 3D geometrical contact models and (3) devising a mechanism for visual verification of hundreds of 3D measurements. The raw and processed data are publicly available from https://isg.nist.gov/deepzoomweb/data/ together with the web -based verification system. Keywords: Co-localization Cellular measurements Cell-scaffold contact Segmentation models Contact evaluation Web-based verification Large-volume 3D image processing”

PLGA melting temperature

Tuesday, December 5, 2017, 8:26 AM ET

Image shows DSC determined melting temperature of a series of PolyVivo PLGA's as well as LA:GA ratio and MW. For very low MW PLGA's, the melting temperature can even be at room temperature or below.

Thermogelling PLGA-PEG-PLGA from PolySciTech used in development of ocular RNA-nanoparticle delivery system

Tuesday, November 28, 2017, 10:20 PM ET

Delivering drugs to the human eye presents a unique set of challenges. Since the injection volume is extremely low and the surrounding tissue is extremely sensitive, care must be taken to use biocompatible carriers with high payload. One means to do this is to use nanoparticles while another is to use thermogelling polymers (ie polymers which transition from a liquid solution at room temperature to a solid gel at body temperature). A powerful delivery technique is to load nanoparticles inside of thermogelling polymers so as to control the release of the nanoparticles. Recently, Researchers at University of Cincinnati, Silpakorn University, Indiana University, and The Ohio State University used PLGA-PEG-PLGA (PolyVivo AK024, AK097) from PolySciTech (www.polyscitech.com) to entrap RNA-nanoparticles and track their distribution in the eye. This research holds promise for providing for more effective ocular drug-delivery. Read more: Shi, Zhanquan, S. Kevin Li, Ponwanit Charoenputtakun, Chia-Yang Liu, Daniel Jasinski, and Peixuan Guo. "RNA nanoparticle distribution and clearance in the eye after subconjunctival injection with and without thermosensitive hydrogels." Journal of Controlled Release (2017). https://www.sciencedirect.com/science/article/pii/S0168365917310246

“Abstract: Thermodynamically and chemically stable RNA nanoparticles derived from the three-way junction (3WJ) of the pRNA from bacteriophage phi29 were examined previously for ocular delivery. It was reported that RNA nanoparticles with tri-way shape entered the corneal cells but not the retinal cells, whereas particle with four-way shape entered both corneal and retinal cells. The present study evaluated ocular delivery of RNA nanoparticles with various shapes and sizes, and assessed the effect of thermosensitive hydrogels (poly(lactic-co-glycolic acid)-b-poly(ethylene glycol)-b-poly(lactic-co-glycolic acid); PLGA-PEG-PLGA) for increasing the retention of RNA nanoparticles in the eye. Fluorescence imaging of mouse eyes and fluorescence microscopy of dissected eye tissues from the conjunctiva, cornea, retina, and sclera were performed to determine the distribution and clearance of the nanoparticles in the eyes after subconjunctival injection in vivo. RNA nanoparticles entered the cells of the conjunctiva, cornea, retina, and sclera after subconjunctival delivery. The clearance of RNA pentagon was slower than both RNA square and triangle of the same designed edge length (10 nm) in the eye, and the clearance of RNA squares of the longer edge lengths (10 and 20 nm) was slower than RNA square of the shorter edge length (5 nm), this indicating that the size could affect ocular pharmacokinetics of the nanoparticles. At 24 h after the injection, approximately 6–10% of the fluorescence signal from the larger nanoparticles in the study (RNA square of 20 nm edge length and RNA pentagon of 10 nm edge length) remained in the eye, and up to 70% of the retinal cells contained the nanoparticles. The results suggest that the larger nanoparticles were “gulped” in conjunctival, corneal, retinal, and scleral cells, similar to the behavior observed in macrophages. Additionally, the combination of RNA nanoparticles with the thermosensitive polymers increased the retention of the nanoparticles in the eye. Keywords: RNA nanoparticle; Double-stranded RNA; Temperature sensitive polymer; Subconjunctival; Ocular delivery”


Wednesday, November 22, 2017, 3:36 PM ET

Akina, Inc. (www.akinainc.com) will be closed Thursday and Friday (11/23-11/24) for the Thanksgiving Holiday. Any orders placed during this time will be filled the following business day. Happy Thanksgiving.

PLA from PolySciTech used in development of nanoparticle-based triple-negative breast cancer therapy

Wednesday, November 15, 2017, 7:44 PM ET

Most forms of breast cancer respond well to conventional therapies, such as doxorubicin. There is, however, a specific type of breast cancer that is referred to as ‘triple-negative’ (named this because it does not have receptors for estrogen, progesterone, or HER2) breast cancer. It is highly resistant to conventional chemotherapy and very invasive. Recently, researchers at University of Cincinnati utilized polylactide (AP128) from PolySciTech (www.polyscitech.com) to develop chemotherapy particles which released gefitinib followed by sequential release of doxorubicin. These particles were found to be significantly more effective at treating triple-negative breast cancer than . This research holds promise for developing more effective chemotherapy strategies to treat breast cancer. Read more: Zhou, Zilan, Mina Jafari, Vishnu Sriram, Jinsoo Kim, Joo-Youp Lee, Sasha J. Ruiz-Torres, and Susan E. Waltz. "Delayed Sequential Co-Delivery of Gefitinib and Doxorubicin for Targeted Combination Chemotherapy." Molecular Pharmaceutics (2017). http://pubs.acs.org/doi/abs/10.1021/acs.molpharmaceut.7b00669

“There are an increasing number of studies showing the order of drug presentation plays a critical role in achieving optimal combination therapy. Here, a nanoparticle design is presented using ion pairing and drug-polymer conjugate for the sequential delivery of gefitinib (Gi) and doxorubicin (Dox) targeting epidermal growth factor receptor (EGFR) signaling applicable for the treatment of triple negative breast cancers. To realize this nanoparticle design, Gi complexed with dioleoyl phosphatidic acid (DOPA) via ion paring was loaded onto the nanoparticle made of Dox-conjugated poly(l-lactide)-block-polyethylene glycol (PLA-b-PEG) and with an encapsulation efficiency of ∼90%. The nanoparticle system exhibited a desired sequential release of Gi followed by Dox, as verified through release and cellular uptake studies. The nanoparticle system demonstrated approximate 4-fold and 3-fold increases in anticancer efficacy compared to a control group of Dox–PLA-PEG conjugate against MDA-MB-468 and A549 cell lines in terms of half maximal inhibitory concentration (IC50), respectively. High tumor accumulation of the nanoparticle system was also substantiated for potential in vivo applicability by noninvasive fluorescent imaging. Keywords: combination therapy; controlled delivery; doxorubicin; EGFR inhibitor; nanoparticles; sequential delivery”

PLGA and PLGA-rhodamine from PolySciTech used in study on chemotherapeutic delivery by nanoparticles

Wednesday, November 15, 2017, 7:41 PM ET

For conventional, loose-drug, chemotherapy, less than 1% of the injected medicine actually makes it to the tumor site. The clinical method for solving this problem has been to inject massive doses of chemotherapeutic agents to the patient, in the hopes that at least some of the medicine makes it to the tumor. This is not a good solution to this problem and leads to substantial morbidity from the side-effects of chemotherapy (hair loss, immune-system damage, etc.). Nanoparticle-based technologies have been developed in the hopes of creating a system in which the drug is encapsulated in a small particle that flows through the blood until it is entrapped by the tumor. Although coating the particle with PEG improves its circulation time, it can also hinder uptake by the tumor. Recently, researchers from Purdue University and Eli Lilly and Company used PLGA (PolyVivo AP020) and Rhodamine-labelled PLGA (Polyvivo AV011) from PolySciTech (www.polyscitech.com) to develop chitosan-coated nanoparticles with preferential tumor attraction over PEGylated nanoparticles. They found, however, that although the particles were preferentially absorbed by the polymer, the drug itself (in the study, ICG tracer-dye was used) leached out too quickly to be of any use. This highlights how critical the drug-entrapment strategy is to the overall design of a nanoparticle formulation. This research holds promise to provide for improved chemotherapeutic strategies with reduced side-effects. Read more: Park, Jinho, Yihua Pei, Hyesun Hyun, Mark A. Castanares, David S. Collins, and Yoon Yeo. "Small molecule delivery to solid tumors with chitosan-coated PLGA particles: A lesson learned from comparative imaging." Journal of Controlled Release (2017). http://www.sciencedirect.com/science/article/pii/S0168365917309367

“Abstract: For polymeric nanoparticles (NPs) to deliver more drugs to tumors than free drug solution, it is critical that the NPs establish interactions with tumor cells and avoid removal from the tumors. Since traditional polyethylene glycol (PEG) surface layer interferes with the cell-NP interaction in tumors, we used a water-soluble and blood-compatible chitosan derivative called zwitterionic chitosan (ZWC) as an alternative surface coating for poly(lactic-co-glycolic acid) (PLGA) NPs. The ZWC-coated PLGA NPs showed pH-dependent surface charge profiles and differential cellular interactions according to the pH of the medium. The in vivo delivery of ZWC-coated NPs was evaluated in mice bearing LS174T-xenografts using magnetic resonance (MR) imaging and fluorescence whole body imaging, which respectively tracked iron oxide particles and indocyanine green (ICG) encapsulated in the NPs as tracers. MR imaging showed that ZWC-coated NPs were more persistent in tumors than PEG-coated NPs, in agreement with the in vitro results. However, the fluorescence imaging indicated that the increased NP retention in tumors by the ZWC coating did not significantly affect the ICG distribution in tumors due to the rapid release of the dye. This study shows that stable drug retention in NPs during circulation is a critical prerequisite to successful translation of the potential benefits of surface-engineered NPs. Keywords: pH-responsive Drug delivery PLGA nanoparticles Small molecules In vivo imaging Encapsulation stability”

PLGA-PEG-NHS from PolySciTech used as part of nanoparticle-protected-islets based treatment of diabetes

Thursday, November 9, 2017, 4:52 PM ET

Type 1 Diabetes is a chronic disease brought on by loss of function of pancreatic islets, groups of cells that produce insulin to regulate the blood sugar content. Recently, transplantation of pancreatic islets has been considered as a long-term treatment for type 1 diabetes that does not require the patient to take daily injections of insulin. Immune-system rejection of the transplant, however, creates difficult for this treatment method as the body attacks the newly transplanted cells. One means of preventing this is to encapsulate the cells in a material which is non-immunogenic so as to protect them from macrophages. Recently, researchers at Yeungnam University, Seoul National University, and Keimyung University (Korea) utilized PolyVivo AI111 (PLGA-PEG-NHS) from PolySciTech (www.polyscitech.com) to create pegylated nanoparticles which attach to the islet cells and prevent them from being attacked by the immune system. This research holds promise to provide for a long-term treatment of diabetes which does not require the patient to continuously inject insulin. Read more: Pham, Tung Thanh, Tiep Tien Nguyen, Shiva Pathak, Shobha Regmi, Hanh Thuy Nguyen, Tuan Hiep Tran, Chul Soon Yong et al. "Tissue adhesive FK506–loaded polymeric nanoparticles for multi–layered nano–shielding of pancreatic islets to enhance xenograft survival in a diabetic mouse model." Biomaterials (2017). http://www.sciencedirect.com/science/article/pii/S014296121730707X

“Abstract: This study aims to develop a novel surface modification technology to prolong the survival time of pancreatic islets in a xenogenic transplantation model, using 3,4–dihydroxyl–l–phenylalanine (DOPA) conjugated poly(lactide–co–glycolide)–poly(ethylene glycol) (PLGA–PEG) nanoparticles (DOPA–NPs) carrying immunosuppressant FK506 (FK506/DOPA–NPs). The functionalized DOPA–NPs formed a versatile coating layer for antigen camouflage without interfering the viability and functionality of islets. The coating layer effectively preserved the morphology and viability of islets in a co–culture condition with xenogenic lymphocytes for 7 days. Interestingly, the mean survival time of islets coated with FK506/DOPA–NPs was significantly higher as compared with that of islets coated with DOPA–NPs (without FK506) and control. This study demonstrated that the combination of surface camouflage and localized low dose of immunosuppressant could be an effective approach in prolonging the survival of transplanted islets. This newly developed platform might be useful for immobilizing various types of small molecules on therapeutic cells and biomaterial surface to improve the therapeutic efficacy in cell therapy and regenerative medicine. Keywords: Surface modification; FK506; Islets transplantation; Local delivery; Diabetes mellitus”

PLGA-PEG-PLGA from PolySciTech used for localized propranolol delivery system

Wednesday, November 1, 2017, 9:12 PM ET

Hemangioma (red or purple colored birthmarks) is a benign childhood tumor generated by excessive growth of blood vessels. Although external hemangioma’s typically only affect aesthetics, the growth of internal hemangiomas, especially near liver, brain, or other critical organs, can cause severe pain and morbidity. Treatment options include corticosteroids and beta-blockers, however applying such treatments to infants and children throughout the whole body in a systemic fashion can create problems with controlling the dose and side-effects. Recently, researchers at Henan Provincial People’s Hospital and the Second Military Medical University (China) used PLGA-PEG-PLGA (PolyVivo AK016) from PolySciTech (www.polyscitech.com) to generate microparticles as part of a local propranolol delivery system. These particles were found to be effective at delivering propranolol (a beta blocker) locally without requiring a large systemic dose. This research holds promise for treating a variety of conditions where excessive angiogenesis is a problem. Read more: Guo, Xiaonan, Xiaoshuang Zhu, Dakan Liu, Yubin Gong, Jing Sun, and Changxian Dong. "Continuous delivery of propranolol from liposomes-in-microspheres significantly inhibits infantile hemangioma growth." International Journal of Nanomedicine 12 (2017): 6923. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5609781/

“Purpose: To reduce the adverse effects and high frequency of administration of propranolol to treat infantile hemangioma, we first utilized propranolol-loaded liposomes-in-microsphere (PLIM) as a novel topical release system to realize sustained release of propranolol. Methods: PLIM was developed from encapsulating propranolol-loaded liposomes (PLs) in microspheres made of poly(lactic-co-glycolic acid)-b-poly(ethylene glycol)-b-poly(lactic-co-glycolic acid) copolymers (PLGA-PEG-PLGA). The release profile of propranolol from PLIM was evaluated, and its biological activity was investigated in vitro using proliferation assays on hemangioma stem cells (HemSCs). Tumor inhibition was studied in nude mice bearing human subcutaneous infantile hemangioma. Results: The microspheres were of desired particle size (~77.8 μm) and drug encapsulation efficiency (~23.9%) and achieved sustained drug release for 40 days. PLIM exerted efficient inhibition of the proliferation of HemSCs and significantly reduced the expression of two angiogenesis factors (vascular endothelial growth factor-A [VEGF-A] and basic fibroblast growth factor [bFGF]) in HemSCs. Notably, the therapeutic effect of PLIM in hemangioma was superior to that of propranolol and PL in vivo, as reflected by significantly reduced hemangioma volume, weight, and microvessel density. The mean hemangioma weight of the PLIM-treated group was significantly lower than that of other groups (saline =0.28 g, propranolol =0.21 g, PL =0.13 g, PLIM =0.03 g; PLIM vs saline: P<0 .001="" a="" and="" approach="" conclusion:="" controlled="" deliver="" density="" efficiently="" findings="" group="" groups="" hemangioma.="" hemangioma="" infantile="" inhibition="" is="" keywords:="" leading="" liposomes="" locally="" lower="" mean="" microsphere="" microvessel="" mm2="" o:p="" of="" other="" our="" p="" pl:="" pl="25" plim-treated="" plim="" promising="" propranolol:="" propranolol="" release="" saline:="" saline="40" show="" significant="" significantly="" site="" than="" that="" the="" to="" very="" vessels="" vs="" was="">

PLGA-Glucose from PolySciTech used in cancer glucose-targeting nanoparticle development for cancer therapy

Tuesday, October 31, 2017, 9:18 PM ET

Cancer cells are typically be considered to act ‘hungry,’ as they consume glucose and oxygen at much faster rates than normal cells. For this, they have over-expressed glucose uptake moieties to absorb more of this energy filled sugar. This provides one method of targeting cancer which is to focus on their over-uptake of glucose as a targeting strategy. Recently, researchers at Seoul National University and Kangwon National University (Korea) utilized PLGA and PLGA-glucose from PolySciTech (www.polyscitech.com) (PolyVivo AP027 (PLGA-glucose) and AP041 (PLGA)) to create nanoparticles which target to the glucose uptake transporters of cancer cells. This research holds promise for improved cancer treatments by targeted delivery. Read more: Park, Ju-Hwan, Hyun-Jong Cho, and Dae-Duk Kim. "Poly ((D, L) lactic-glycolic) acid–star glucose nanoparticles for glucose transporter and hypoglycemia-mediated tumor targeting." International Journal of Nanomedicine 12 (2017): 7453. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5644567/

“Poly((D,L)lactic-glycolic)acid–star glucose (PLGA-Glc) polymer-based nanoparticles (NPs) were fabricated for tumor-targeted delivery of docetaxel (DCT). NPs with an approximate mean diameter of 241 nm, narrow size distribution, negative zeta potential, and spherical shape were prepared. A sustained drug release pattern from the developed NPs was observed for 13 days. Moreover, drug release from PLGA-Glc NPs at acidic pH (endocytic compartments and tumor regions) was significantly improved compared with that observed at physiological pH (normal tissues and organs). DCT-loaded PLGA-Glc NPs (DCT/PLGA-Glc NPs) exhibited an enhanced antiproliferation efficiency rather than DCT-loaded PLGA NPs (DCT/PLGA NPs) in Hep-2 cells, which can be regarded as glucose transporters (GLUTs)-positive cells, at ≥50 ng/mL DCT concentration range. Under glucose-deprived (hypoglycemic) conditions, the cellular uptake efficiency of the PLGA-Glc NPs was higher in Hep-2 cells compared to that observed in PLGA NPs. Cy5.5-loaded NPs were prepared and injected into a Hep-2 tumor-xenografted mouse model for in vivo near-infrared fluorescence imaging. The PLGA-Glc NPs group exhibited higher fluorescence intensity in the tumor region than the PLGA NPs group. These results imply that the PLGA-Glc NPs have active tumor targeting abilities based on interactions with GLUTs and the hypoglycemic conditions in the tumor region. Therefore, the developed PLGA-Glc NPs may represent a promising tumor-targeted delivery system for anticancer drugs. Keywords: PLGA-Glc, nanoparticles, glucose transporter, hypoxia, tumor targeting”

PLGA and PLCL from PolySciTech used in development of biodegradable foam for advanced wound treatment

Tuesday, October 24, 2017, 6:49 PM ET

One means to encourage wound healing, in either chronic or traumatic wounds, is to reduce the pressure across the wound surface to encourage local blood-flow, stimulate healing, and draw out excess fluids. This requires placing a sterile foam over the top of the wound and connecting the foam to a vacuum pump with an air-tight cover to apply vacuum to the wound. Conventionally, this is done with a non-degradable polyurethane-type foam. During this treatment, tissue often grows into the foam, which creates significant problems upon changing the dressing as fresh-grown tissue can be damaged. Recently, researchers at Wake Forest University utilized multiple PLGA, PLCL, and PCL products (PolyVivo AP037, AP081, AP036, AP073, AP013, and AP015) from PolySciTech (www.polyscitech.com) to develop a degradable, compressible foam for wound therapy. This research holds promise for development of improved wound-therapy methods using foams that simply resorb into the body rather than have problems with in-growth. Read more: Warner, Harleigh J., and William D. Wagner. "Fabrication of biodegradable foams for deep tissue negative pressure treatments." Journal of Biomedical Materials Research Part B: Applied Biomaterials. http://onlinelibrary.wiley.com/doi/10.1002/jbm.b.34007/full

“ABSTRACT: Devices for negative pressure wound therapy (NPWT) rely on compressible foams operating at the tissue-device interface. Clinically used foams are nonabsorbable and if used on deep wounds or left in place for an extended period of time, excessive cell ingrowth and formation of granulation tissue into the foam may require a surgical procedure to remove the foam. Foams with fast degradation and with low immunogenicity and fibrotic response are required. Foams composed of combinations of poly(lactide-co-glycolide) (PLGA), poly(lactide-co-caprolactone) (PLCL), and polycaprolactone (PCL) were created by combined salt leaching and solvent displacement protocols. In vitro and in vivo degradation studies and mechanical properties of foams were evaluated and compared to clinically used poly(vinyl alcohol) (PVA) foam and PCL foams. Foams composed of PLGA (50:50 lactide:glycolide) of low molecular weight blended with PCL maintained mechanical properties and degraded significantly after 21 days of subcutaneous implantation in rats. The most ideal formulations for use in NPWT were identified as copolymeric PLGA (Mn 3000 Da) at a lactide:glycolide ratio of 50:50 combined with PCL at either a 75:25 or 50:50 ratio, and copolymeric PLGA (Mn 7500 Da) at a lactide:glycolide ratio of 50:50 combined with PCL at a 50:50 ratio. KeyWords: polyester, polycaprolactone, poly(lactic-co-glycolic acid), foams, negative pressure wound therapy”

These posts are syndicated from John Garner's blog at http://jgakinainc.blogspot.com/.

Post a question or comment at the blog, or at hyperactivepolymer.com.


Social Media

Facebook Twitter Google+ LinkedIn Google Blogger Hyperactive polymer ACS network

Help us improve. We welcome your feedback: SIGN IN or be ANONYMOUS.

logoHome Page | Copyright 2018 Akina, Incorporated | 3495 Kent Avenue, West Lafayette, Indiana 47906 | (765) 464-0390
Official website of Akina, Inc.