Akina
Technical Blog
John GarnerJohn Garner, General Manager

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


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PEG-PLGA from PolySciTech utilized in development of nanoparticle that modifies tumor microenvironment for improved chemotherapy

Friday, December 2, 2022, 3:33 PM ET


In living systems, cancerous tumors create a unique, local microenvironment by a variety of mechanisms. One of these is the effect of the cancer itself which consumes resources and oxygen faster than the body can provide it leading to areas of low oxygen content. Additionally cancer acts to suppress the immune system in its local area. Often, these unusual conditions surrounding the growing cancer impedes the effects of chemotherapy agents. Recently, researchers at the Chinese Academy of Sciences utilized PEG-PLGA (Cat AK010) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) as part of a multifunctional nanoparticle and tested this for its ability to restore the microenvironment of cancer to conditions under which drugs can be more effective. This research holds promise to improve treatments against this often fatal disease. Read more: Li, Lei, Mingming Zhen, Haoyu Wang, Zihao Sun, Xinran Cao, Jie Li, Shuai Liu et al. "Tumor microenvironment-modulated multiple nanotherapeutic system for potent cancer immunotherapy and metastasis inhibition." Nano Today 48 (2023): 101702. https://www.sciencedirect.com/science/article/pii/S1748013222003309

“Highlights: This nanotherapeutic system could validly relieve tumor hypoxia and induce M2 to M1 polarization of tumor-associated macrophages to reverse immunosuppression, serving for TME reprogramming. This nanotherapeutic system stimulates dendritic cells maturation, thereby initiating T-cell-mediated anti-tumor immune response. The nanotherapeutic system eliminates primary tumor and efficiently inhibits tumor metastasis without obvious adverse effects. The nanotherapeutic system creates superior synergistic cancer immunotherapy combined with anti-PD-L1 immune checkpoint inhibitor. Abstract: The hypoxic and immunosuppressive tumor microenvironment (TME) generally weaken the efficacy of immunotherapy in solid tumors. However, reversing TME remains a formidable challenge. Here, an elaborately multitasking nanotherapeutic system (PEG-PLGA-R848@GFCNs) is demonstrated to forceful remodel TME. This nanotherapeutic system could validly relieve tumor hypoxia and induce M2 to M1 polarization of tumor-associated macrophages (TAMs) to reverse immunosuppression, serving for TME reprogramming. Furthermore, PEG-PLGA-R848@GFCNs stimulates dendritic cells maturation, thereby initiating T-cell-mediated anti-tumor immune response. Of note, the nanotherapeutic system eliminates primary tumor that established by 4T1 tumor models in mice and efficiently inhibits B16F10 melanoma metastasis without obvious adverse effects. Importantly, PEG-PLGA-R848@GFCNs combined with anti-PD-L1 immune checkpoint inhibitor achieves superior synergistic cancer immunotherapy. Collectively, our work offers a reliable and safe strategy to fabricate a multitasking nanotherapeutic system for comprehensively modulating TME to achieve effective cancer immunotherapy and metastasis inhibition. This multitasking nanotherapeutic system could validly relieve tumor hypoxia and induce M2 to M1 polarization of tumor-associated macrophages to reverse immunosuppression, serving for tumor microenvironment reprogramming, which not only eliminates primary tumor and efficiently inhibit tumor metastasis, but could create superior synergistic cancer immunotherapy combined with anti-PD-L1 immune checkpoint inhibitor. Keywords: Cancer immunotherapy Immunosuppressive tumor microenvironment Tumor hypoxia relief Gado fullerene nanoparticles Immune checkpoint inhibitor”


PLGA from PolySciTech used in development of oral microparticles for localized colon delivery of 5FU as colorectal cancer treatment

Thursday, December 1, 2022, 4:56 PM ET


Under normal oral drug delivery conditions, it is desired for the medicine to be released in the small intestine, or before if it is stable in acid, and to uptake across the lumen into the bloodstream. However, for treating issues located in the colorectal area, better drug delivery is achieved by designing a formulation which delays release beyond the small intestine and delivers the drug directly into the large intestine and colorectal area. This can be utilized to achieve localized delivery to a portion of the body which is not normally the target for localized delivery. Researchers at Pusan National University and Korea University utilized PLGA (AP037) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to develop chemotherapeutic, 5-FU, loaded microparticles designed to pass through the stomach and intestines before releasing the drug into the colon for targeted treatment of colorectal cancer. This research holds promise to provide for improved treatment against cancer. Read more: Lee, Juho, Junhwan Bae, Dongmin Kwak, Hyunwoo Kim, Jihyun Kim, Shwe Phyu Hlaing, Aruzhan Saparbayeva et al. "5-Fluorouracil crystal-incorporated, pH-responsive, and release-modulating PLGA/Eudragit FS hybrid microparticles for local colorectal cancer-targeted chemotherapy." International Journal of Pharmaceutics (2022): 122443. https://www.sciencedirect.com/science/article/pii/S037851732200998X

“Abstract: 5-Fluorouracil (5-FU) is a widely used chemotherapeutic agent for colorectal cancer (CRC) owing to its potent anticancer effects. However, severe systemic side effects and poor drug accumulation in the CRC tissues limit its efficacy. This study aimed to develop 5-FU crystal-incorporated, pH-responsive, and release-modulating poly(d,l-lactide-co-glycolide)/Eudragit FS hybrid microparticles (5FU-EPMPs) for the local CRC-targeted chemotherapy. Approximately 150 μm 5FU-EPMPs were fabricated via the S/O/W emulsion solvent evaporation method, with 7.93 ± 0.24% and 87.23 ± 2.64% 5-FU loading and encapsulation efficiencies, respectively. Drug release profiles in a simulated pH environment of the gastrointestinal tract revealed that premature 5-FU release in the stomach and small intestine was prevented, thereby minimizing systemic 5-FU absorption. After reaching the colon, 5-FU was continuously released for >15 h, allowing long-term exposure of CRC tissues to sufficient 5-FU concentrations. Furthermore, in a CRC mouse model, the 5FU-EPMPs showed potent inhibition of tumor growth without signs of systemic toxicity. Thus, the 5FU-EPMPs represent a promising drug delivery system for local CRC-targeted chemotherapy. Keywords: 5-fluorouracil pH-responsive release modulation colorectal cancer colon-targeted delivery local chemotherapy.”


PLGA-PEG-Mal, PLGA-CY5 from PolySciTech used in development of triple-negative breast-cancer targeting nanoparticles

Tuesday, November 22, 2022, 9:45 AM ET



Cancer is a widely diverse set of disease states with a single moniker to describe, in general, any overgrowth of human tissue. Because of their diversity, the method to treat the cancer must be optimized to the exact type of cancer. Most types of breast cancer respond well to modern therapy based on their specific markers. For example, most HER2+ type breast cancers respond well to treatments utilizing herceptin which targets the HER2 receptor. However, a form of breast cancer which lacks the three most common receptors, so called “triple-negative” breast cancer is very difficult to treat as these conventional therapies are ineffective to that particular type of cancer. Recently, researchers at University of Maryland utilized Methoxy-terminated PLGA−PEG (10:5 kDa) (Cat# AK010), PLGA−PEG with maleimide end group (PLGA−PEGMal, 10:5 kDa) (Cat# AI053), and PLGA-Cyanine 5 (PLGA-Cy5, 30−55 kDa) (Cat# AV034) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to create fn-14 targeted nanoparticles for therapy against triple-negative breast cancer that has metastasized into the brain. This research holds promise to improve therapies against this very difficult to treat form of cancer. Read more: Carney, Christine P., Anshika Kapur, Pavlos Anastasiadis, Rodney M. Ritzel, Chixiang Chen, Graeme F. Woodworth, Jeffrey A. Winkles, and Anthony J. Kim. "Fn14-Directed DART Nanoparticles Selectively Target Neoplastic Cells in Preclinical Models of Triple-Negative Breast Cancer Brain Metastasis." Molecular Pharmaceutics (2022). https://pubs.acs.org/doi/abs/10.1021/acs.molpharmaceut.2c00663

“Triple-negative breast cancer (TNBC) patients with brain metastasis (BM) face dismal prognosis due to the limited therapeutic efficacy of the currently available treatment options. We previously demonstrated that paclitaxel-loaded PLGA–PEG nanoparticles (NPs) directed to the Fn14 receptor, termed “DARTs”, are more efficacious than Abraxane─an FDA-approved paclitaxel nanoformulation─following intravenous delivery in a mouse model of TNBC BM. However, the precise basis for this difference was not investigated. Here, we further examine the utility of the DART drug delivery platform in complementary xenograft and syngeneic TNBC BM models. First, we demonstrated that, in comparison to nontargeted NPs, DART NPs exhibit preferential association with Fn14-positive human and murine TNBC cell lines cultured in vitro. We next identified tumor cells as the predominant source of Fn14 expression in the TNBC BM-immune microenvironment with minimal expression by microglia, infiltrating macrophages, monocytes, or lymphocytes. We then show that despite similar accumulation in brains harboring TNBC tumors, Fn14-targeted DARTs exhibit significant and specific association with Fn14-positive TNBC cells compared to nontargeted NPs or Abraxane. Together, these results indicate that Fn14 expression primarily by tumor cells in TNBC BMs enables selective DART NP delivery to these cells, likely driving the significantly improved therapeutic efficacy observed in our prior work.”


PLGA-NH2 from PolySciTech used in development of polypeptide capped nanoparticles for treatment of ovarian cancer

Tuesday, November 15, 2022, 4:17 PM ET



Active targeting holds great potential for treatment of many disease states including improved drug delivery to cancer cells. In this method a biodegradable nanoparticle is loaded with a active pharmaceutical (drug) and surface modified to provide for selectively sticky ligands which attach to selected sites on cancer cells or in tumors. Recently, researchers at The City University of New York and Icahn School of Medicine, used PLGA-amine (Cat# AI010) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to create RGD end capped particles loaded with combretastatin A4. They tested this for treatment against ovarian cancer. This research holds promise to improve therapies against this lethal disease. Read more: Dragulska, Sylwia A., Mina Poursharifi, Ying Chen, Marek T. Wlodarczyk, Maxier Acosta Santiago, Peter Dottino, John A. Martignetti, and Aneta J. Mieszawska. "Engineering and Validation of a Peptide-Stabilized Poly (lactic-co-glycolic) Acid Nanoparticle for Targeted Delivery of a Vascular Disruptive Agent in Cancer Therapy." Bioconjugate Chemistry (2022). https://pubs.acs.org/doi/abs/10.1021/acs.bioconjchem.2c00418

“ABSTRACT: Developing a biocompatible and biodegradable nanoparticle (NP) carrier that integrates drug-loading capability, active targeting, and imaging modality is extremely challenging. Herein, we report an NP with a core of poly(lactic-coglycolic) acid (PLGA) chemically modified with the drug combretastatin A4 (CA4), a vascular disrupting agent (VDA) in clinical development for ovarian cancer (OvCA) therapy. The NP is stabilized with a short arginine-glycine-aspartic acid phenylalanine x3 (RGDFFF) peptide via self-assembly of the peptide on the PLGA surface. Importantly, the use of our RGDFFF coating replaces the commonly used polyethylene glycol (PEG) polymer that itself often induces an unwanted immunogenic response. In addition, the RGD motif of the peptide is well-known to preferentially bind to αvβ3 integrin that is implicated in tumor angiogenesis and is exploited as the NP’s targeting component. The NP is enhanced with an optical imaging fluorophore label via chemical modification of the PLGA. The RGDFFF-CA4 NPs are synthesized using a nanoprecipitation method and are ∼75 ± 3.7 nm in diameter, where a peptide coating comprises a 2−3 nm outer layer. The NPs are serum stable for 72 h. In vitro studies using human umbilical cord vascular endothelial cells (HUVEC) confirmed the high uptake and biological activity of the RGDFFF-CA4 NP. NP uptake and viability reduction were demonstrated in OvCA cells grown in culture, and the NPs efficiently accumulated in tumors in a preclinical OvCA mouse model. The RGDFFF NP did not induce an inflammatory response when cultured with immune cells. Finally, the NP was efficiently taken up by patient-derived OvCA cells, suggesting a potential for future clinical applications.”


New Product: RiPurpose polyethylene terephthalate prepolymer for upcycled, green polymer synthesis

Thursday, November 3, 2022, 12:45 PM ET


Akina, Inc, in partnership with RiKarbon (https://rikarbon.com/) is providing RiPuroposeTM PET prepolymer. You can learn more and see ordering details here https://akinainc.com/polyscitech/products/ripurpose/index.php

RiPurpose Oligomer is produced by the chemical breakdown of post-consumer waste polyethylene terephthalate (PET) plastic collected from the ocean and environment. This sustainable and green co-monomer can be used as a direct replacement for petroleum-derived feedstock to produce high-value renewable and upcycled polymers by polycondensation and transesterification reactions. RiPurpose Olig1000-700 can be directly used as a feedstock during the polycondensation step of PET production, thereby avoiding the esterification step to prepare a prepolymer intermediate. By using this recycled feedstock, customers can claim CO2 emission reduction of up to 60% for their end-use polymers. The material can also be utilized as an initiator for ring-opening polymerization of various monomers, such as caprolactone, which can be used to make PET-co-caprolactone copolymers that can be utilized as compatibilizers in polymer blends. Additionally, polycondensation can be performed with a wide variety of materials to create novel polymeric materials. An example of this is the co-reaction between PET and poly(tetramethylene oxide) which has been reported recently in literature for the creation of versatile multi-blocks segmented poly(ether-ester)s such as poly(ethylene terephthalate-co-1,4-cyclohexanedimethylene terephthalate)-block-poly(tetramethylene oxide) which has highly controlled melt and mechanical properties. Further modification of the polymer can be achieved by initially reacting it with an excess quantity of ethylene glycol under polycondensation to convert the precursor into a di-alcohol endcap product. This can subsequently be reacted with isothiocyanates to form PET-polyurethanes in which case the PET behaves as a chain extender in the stepwise reaction. Similarly, a reaction with diglycidyl compounds can be used for the preparation of epoxies. Conversely, a reaction with excess terephthalic acid can convert into a diacid form. This can subsequently be reacted with diamines in a polycondensation condition to form polyamides. The potential applications for this versatile precursor are diverse and hold great promise for further development. RiPurpose Patent Pending (US Provisional Patent# 63/312519)


PLGA-PEG-PLGA from PolySciTech used in development of gel for treatment of nerve-damage and paralysis

Monday, October 31, 2022, 4:22 PM ET



PLGA-PEG-PLGA is a polymer which can dissolve in cold water and form into a gel at increased temperature and, as such, is referred to as a thermogel. Peripheral nerve injury (PNI) is a significant medical issue occurring in approximately 3% of all trauma patients and often leads to paralysis or malfunction of affected parts of the body. Erythropoietin (EPO) is an endogenous stimulant of vessel growth and can aid in tissue repair by promoting cell proliferation and vasculogenesis. Recently, researchers at Pennsylvania State University and University of Arizona used PLGA-PEG-PLGA (PolyVivo cat# AK097) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to create an EPO loaded thermogel and researched the use of this for treatment of PNI. This research holds promise to improve the treatment of PNI and reduce the incidence of nerve-damage induced paralysis. Read more: Manto, Kristen M., Prem Kumar Govindappa, Brandon Martinazzi, Aijie Han, John P. Hegarty, Zachary Koroneos, M. A. Talukder, and John C. Elfar. "Erythropoietin-PLGA-PEG as a local treatment to promote functional recovery and neurovascular regeneration after peripheral nerve injury." Journal of Nanobiotechnology 20, no. 1 (2022): 1-17. https://jnanobiotechnology.biomedcentral.com/articles/10.1186/s12951-022-01666-5

“Abstract: Background: Traumatic peripheral nerve injury (TPNI) is a major medical problem with no universally accepted pharmacologic treatment. We hypothesized that encapsulation of pro-angiogenic erythropoietin (EPO) in amphiphilic PLGA-PEG block copolymers could serve as a local controlled-release drug delivery system to enhance neurovascular regeneration after nerve injury. Methods: In this study, we synthesized an EPO-PLGA-PEG block copolymer formulation. We characterized its physiochemical and release properties and examined its effects on functional recovery, neural regeneration, and blood vessel formation after sciatic nerve crush injury in mice. Results: EPO-PLGA-PEG underwent solution-to-gel transition within the physiologically relevant temperature window and released stable EPO for up to 18 days. EPO-PLGA-PEG significantly enhanced sciatic function index (SFI), grip strength, and withdrawal reflex post-sciatic nerve crush injury. Furthermore, EPO-PLGA-PEG significantly increased blood vessel density, number of junctions, and myelinated nerve fibers after injury. Conclusion: This study provides promising preclinical evidence for using EPO-PLGA-PEG as a local controlled-release treatment to enhance functional outcomes and neurovascular regeneration in TPNI.”


PLGA-amine from PolySciTech used in development of doxorubicin delivery for bone cancer therapy

Thursday, October 27, 2022, 4:47 PM ET



Bone cancer is difficult to treat due to the poor vascularization and drug delivery in bone tissue. Researchers from Seoul National University used PLGA-NH2 (Cat# AI017) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to create alendronate-decorated PLGA-chondroitin sulfate particles for bone-tissue targeting. This research holds promise to improve treatments for this potentially fatal disease. Read more: Kang, Nae-Won, Voradanu Visetvichaporn, Duy-Thuc Nguyen, Da-Han Kim, Min-Jae Kim, So-Yeol Yoo, Jae-Young Lee, and Dae-Duk Kim. "Bone Tumor-Homing Nanotherapeutics for Prolonged Retention in Tumor Microenvironment and Facilitated Apoptotic Process Via Mevalonate Pathway Inhibition." Available at SSRN 4155152. https://papers.ssrn.com/sol3/papers.cfm?abstract_id=4155152

“Bone malignancy features a mineralized extracellular matrix primarily composed of hydroxyapatite, which interferes with the distribution and activity of antineoplastic agents. Herein, we report bone tumor-homing polymeric nanotherapeutics consisting of alendronate-decorated chondroitin sulfate A-graft-poly(lactide-co-glycolide) and doxorubicin (DOX), named PLCSA-AD, which displayed a prolonged retention profile in the tumor microenvironment and augmented therapeutic efficacy via inhibition of the mevalonate pathway. PLCSA-AD exhibited a 1.72-fold lower IC50 value than free DOX and a higher affinity for hydroxyapatite than PLCSA in HOS/MNNG cell-based 2D bone tumor-mimicking models. The inhibition of the mevalonate pathway by PLCSA-AD in tumor cells was verified by investigating the cytosolic fraction of unprenylated proteins, where blank PLCSA-AD significantly increased the expression of cytosolic Ras and RhoA without changing their total cellular amounts. In a bone tumor-mimicking xenografted mouse model, AD-decorated nanotherapeutics significantly increased tumor accumulation (1.73-fold) compared with PLCSA, and higher adsorption to hydroxyapatites was observed in the histological analysis of the tumor. As a result, inhibition of the mevalonate pathway and improvement in tumor accumulation led to markedly enhanced therapeutic efficacy in vivo, suggesting that PLCSA-AD could be promising nanotherapeutics for bone tumor treatment. Keywords: bone tumors, alendronate, mevalonate pathway inhibition, hydroxyapatites, tumor distribution, apoptosis”


New Product: AKiNAfil™ 3D Printer Filament

Monday, October 24, 2022, 4:20 PM ET



Conventional 3D printing filament either consists of non-degradable polymers such as Acrylonitrile butadiene styrene (ABS) or slowly degradable polymers such as high molecular weight polylactide (PLA) or Polyethylene terephthalate glycol (PETG). The PLA conventionally used in 3D printers has a degradation time of several decades which may be useful for environmental composting considerations but is not useful for biomedical applications which need resorption times in weeks to months. For biomedical applications, resorbable PLGA provides superior performance.

Using a custom-modified Filabot EX2 extrusion kit with extrusion under argon flush conditions, Akina, Inc. has reformatted bioresorbable polymers to standardized 1.7 mm filament available in a variety of lengths including 6-meter sections (~15-18g) and 1-meter sections (~2-3g). These coils are packed with protective desiccant and are unspooled for customers to use with any spool of their choice. The materials contain an FDA generally regarded as safe (GRAS) plasticizer (acetyltriethylcitrate, ATEC) to improve processability. These polymers have been modified for use in most conventional 3D printers. See more here https://akinainc.com/polyscitech/products/akinafil/index.php




PEG-PLA from PolySciTech used in development of Monoclonal antibody labeled nanoparticles for targeted delivery.

Thursday, October 13, 2022, 4:54 PM ET



The ability to direct and target nanoparticles towards desired cells or tissues is a powerful therapeutic technique which can address many disease states. This is not a trivial task in the human body for many reasons including rapid clearance of particles from the bloodstream by organs such as the liver or kidneys as well as immune attack against the particles. Recently, researchers at Yale University and New York University PEG-PLA (cat# AK054), PLA-PEG-COOH (cat# AI030), PLA-PEG-mal (cat# AI065) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to development broadly applicable Mab targeted nanoparticles and tested these for perfusion models. This research holds promise to improve targeted nano-therapies in the future. Read More: C. Albert, L. Bracaglia, A. Koide, J. DiRito, T. Lysyy, L. Harkins, C. Edwards, O. Richfield, J. Grundler, K. Zhou, E. Denbaum, G. Ketavarapu, T. Hattori, S. Perincheri, J. Langford, A. Feizi, D. Haakinson, S. A. Hosgood, M. L. Nicholson, J. S. Pober, W. M. Saltzman, S. Koide, G. T. Tietjen “Monobody adapter for functional antibody display on nanoparticles for adaptable targeted delivery applications” Nature Communications volume 13, Article number: 5998 (2022) https://www.nature.com/articles/s41467-022-33490-8

“Abstract: Vascular endothelial cells (ECs) play a central role in the pathophysiology of many diseases. The use of targeted nanoparticles (NPs) to deliver therapeutics to ECs could dramatically improve efficacy by providing elevated and sustained intracellular drug levels. However, achieving sufficient levels of NP targeting in human settings remains elusive. Here, we overcome this barrier by engineering a monobody adapter that presents antibodies on the NP surface in a manner that fully preserves their antigen-binding function. This system improves targeting efficacy in cultured ECs under flow by >1000-fold over conventional antibody immobilization using amine coupling and enables robust delivery of NPs to the ECs of human kidneys undergoing ex vivo perfusion, a clinical setting used for organ transplant. Our monobody adapter also enables a simple plug-and-play capacity that facilitates the evaluation of a diverse array of targeted NPs. This technology has the potential to simplify and possibly accelerate both the development and clinical translation of EC-targeted nanomedicines.”


Fluorescent PLGA from PolySciTech used in research on cell morphology and behavior on top of fiber scaffolds

Wednesday, October 12, 2022, 2:05 PM ET



Tissue regeneration is a process by which damaged or missing tissue is replaced by providing the correct conditions for cells to regrow. For this the extracellular matrix (the material which binds between cells) must be replaced and this is often accomplished with a fibrous or porous cell scaffold. Research is ongoing whether such artificial cell scaffolds can provide the correct environment for cells to grow and to behave as they normally do in the body. Recently, researchers at the National Institute of Standards and Technology (NIST) used fluorescently labeled PLGA (AV015) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to research cell behavior when grown on mesh scaffolds. This research can help further understanding and development of tissue regeneration strategies in the future. Read more: Florczyk, S.J., Hotaling, N.A., Simon, M., Chalfoun, J., Horenberg, A.L., Schaub, N.J., Wang, D., Szczypiński, P.M., DeFelice, V.L., Bajcsy, P. and Simon Jr, C.G., 2022. Measuring dimensionality of cell‐scaffold contacts of primary human bone marrow stromal cells cultured on electrospun fiber scaffolds. Journal of Biomedical Materials Research Part A. https://onlinelibrary.wiley.com/doi/abs/10.1002/jbm.a.37449

“Abstract: The properties and structure of the cellular microenvironment can influence cell behavior. Sites of cell adhesion to the extracellular matrix (ECM) initiate intracellular signaling that directs cell functions such as proliferation, differentiation, and apoptosis. Electrospun fibers mimic the fibrous nature of native ECM proteins and cell culture in fibers affects cell shape and dimensionality, which can drive specific functions, such as the osteogenic differentiation of primary human bone marrow stromal cells (hBMSCs), by. In order to probe how scaffolds affect cell shape and behavior, cell-fiber contacts were imaged to assess their shape and dimensionality through a novel approach. Fluorescent polymeric fiber scaffolds were made so that they could be imaged by confocal fluorescence microscopy. Fluorescent polymer films were made as a planar control. hBSMCs were cultured on the fluorescent substrates and the cells and substrates were imaged. Two different image analysis approaches, one having geometrical assumptions and the other having statistical assumptions, were used to analyze the 3D structure of cell-scaffold contacts. The cells cultured in scaffolds contacted the fibers in multiple planes over the surface of the cell, while the cells cultured on films had contacts confined to the bottom surface of the cell. Shape metric analysis indicated that cell-fiber contacts had greater dimensionality and greater 3D character than the cell-film contacts. These results suggest that cell adhesion site-initiated signaling could emanate from multiple planes over the cell surface during culture in fibers, as opposed to emanating only from the cell's basal surface during culture on planar surfaces.”


PLGA from PolySciTech used to create hyaluronic-acid coated nanoparticles for targeting of macrophages for inflammation treatment

Tuesday, October 11, 2022, 4:51 PM ET


Ulcerative colitis is an inflammatory bowel disease (IBD) that causes inflammation and ulcers (sores) in the digestive tract. Recently, researchers at Pusan National University (Korea) and Guizhou Medical University (China) PLGA (Cat# AP082) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to develop nanoparticles for treatment of inflammation. This research holds promise for treatment of inflammatory bowel disease (IBD). Read more: Hlaing, Shwe Phyu, Jiafu Cao, Juho Lee, Jihyun Kim, Aruzhan Saparbayeva, Dongmin Kwak, Hyunwoo Kim et al. "Hyaluronic Acid-Conjugated PLGA Nanoparticles Alleviate Ulcerative Colitis via CD44-Mediated Dual Targeting to Inflamed Colitis Tissue and Macrophages." Pharmaceutics 14, no. 10 (2022): 2118. https://www.mdpi.com/1868638

“Abstract: Although various local anti-inflammatory therapies for ulcerative colitis have been developed, rapid drug elimination from inflamed colitis tissue and off-target side effects reduce their therapeutic efficacy. In this study, we synthesized curcumin (Cur)-loaded hyaluronic acid (HA)-conjugated nanoparticles (Cur-HA-PLGA-NPs) that target inflamed colitis tissue via HACD44 interaction with resident colonic epithelial cells and subsequently target activated macrophages for ulcerative colitis therapy. The synthesized spherical Cur-HA-PLGA-NPs showed physicochemical properties similar to those of non-HA-conjugated Cur-PLGA-NPs. HA-PLGANPs exhibited selective accumulation in inflamed colitis tissue with minimal accumulation in healthy colon tissue. HA functionalization enhanced targeted drug delivery to intestinal macrophages, significantly increasing HA-PLGA-NP cellular uptake. Importantly, the rectal administration of Cur-HA-PLGA-NPs exhibited better therapeutic efficacy than Cur-PLGA-NPs in animal studies. Histological examination revealed that Cur-HA-PLGA-NPs reduced inflammation with less inflammatory cell infiltration and accelerated recovery with re-epithelialization signs. Our results suggest that Cur-HA-PLGA-NPs are a promising delivery platform for treating ulcerative colitis. Keywords: ulcerative colitis therapy; inflamed tissue targeting; macrophage targeting; nanoparticle; hyaluronic acid”


PLGA-PEG-Mal and PLGA-CY5 from PolySciTech used in development of nanoparticles with targeted delivery to white blood cells

Tuesday, October 11, 2022, 3:44 PM ET


Neutrophils are a type of white blood cell (leukocytes) that act as your immune system's first line of defense. The ability to modify their behavior can be a powerful tool for controlling both immune diseases and potentially immunotherapy against cancer or other targets. Recently, researchers at Hebrew University, Tel Aviv University, and Immunyx Pharma PLGA-CY5 (cat# AV034) and PLGA-PEG-Maleimide (cat# AI110) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to create targeted nanoparticles with ligands to target and attach to neutrophils. This research holds promise to provide for mechanisms to modify and modulate the behavior of neutrophils as therapeutic strategy. Read More: Granot, Z., Völs, S., Kaisar-Iluz, N., Shaul, M.E., Ryvkin, A., Ashkenazy, H., Yehuda, A., Atamneh, R., Meital, B.D.N., Nadav, M. and Hirsch, S., Targeted Nanoparticles Modify Neutrophil Function In Vivo. Frontiers in Immunology, p.5679. https://www.frontiersin.org/articles/10.3389/fimmu.2022.1003871/full

“Abstract: Neutrophils play critical roles in a broad spectrum of clinical conditions. Accordingly, manipulation of neutrophil function may provide a powerful immunotherapeutic approach. However, due to neutrophils characteristic short half-life and their large population number, this possibility was considered impractical. Here we describe the identification of peptides which specifically bind either murine or human neutrophils. Although the murine and human neutrophil-specific peptides are not cross-reactive, we identified CD177 as the neutrophil-expressed binding partner in both species. Decorating nanoparticles with a neutrophil-specific peptide confers neutrophil specificity and these neutrophil-specific nanoparticles accumulate in sites of inflammation. Significantly, we demonstrate that encapsulating neutrophil modifying small molecules within these nanoparticles yields specific modulation of neutrophil function (ROS production, degranulation, polarization), intracellular signaling and longevity both in vitro and in vivo. Collectively, our findings demonstrate that neutrophil specific targeting may serve as a novel mode of immunotherapy in disease.”


Fluorescent PLGA from PolySciTech used in development of gene-editing therapy for treatment of cystic fibrosis

Tuesday, October 11, 2022, 3:40 PM ET



Cystic fibrosis (CF) is an autosomal recessive disorder caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. Gene-editing technology could treat this disease at the source by altering the DNA to provide for a corrected CFTR gene. Recently, researchers at Yale University used PLGA-CY5 (Cat# AV034) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to create nanoparticles that were fluorescently traceable. They used these for testing a delivery mechanism of peptide nucleic acid gene editing technology as a therapy for CF. This research holds promise to improve treatment of this fatal disease. Read More: Piotrowski-Daspit, A.S., Barone, C., Lin, C.Y., Deng, Y., Wu, D., Binns, T.C., Xu, E., Ricciardi, A.S., Putman, R., Garrison, A. and Nguyen, R., 2022. In vivo correction of cystic fibrosis mediated by PNA nanoparticles. Science Advances, 8(40), p.eabo0522. https://www.science.org/doi/abs/10.1126/sciadv.abo0522

“Abstract: Cystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. We sought to correct the multiple organ dysfunction of the F508del CF-causing mutation using systemic delivery of peptide nucleic acid gene editing technology mediated by biocompatible polymeric nanoparticles. We confirmed phenotypic and genotypic modification in vitro in primary nasal epithelial cells from F508del mice grown at air-liquid interface and in vivo in F508del mice following intravenous delivery. In vivo treatment resulted in a partial gain of CFTR function in epithelia as measured by in situ potential differences and Ussing chamber assays and correction of CFTR in both airway and GI tissues with no off-target effects above background. Our studies demonstrate that systemic gene editing is possible, and more specifically that intravenous delivery of PNA NPs designed to correct CF-causing mutations is a viable option to ameliorate CF in multiple affected organs.”


PLGA from PolySciTech used in the development of oral insulin delivery nanoparticles

Tuesday, October 11, 2022, 2:25 PM ET



Insulin is a necessary component for the treatment of diabetes. Due to its fragile nature and poor bioavailability, it is not viable to normally take insulin in conventional oral form such as via tablet or capsule. For this reason, it is necessary to normally take insulin as an injection. Recently, researchers at The University of Queensland (Australia) utilized PLGA from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to develop a nanoparticle for delivery of insulin through oral route. This research may provide for improved therapies against diabetes. Read more: Pang, Huiwen, Xiangquan Huang, Zhi Ping Xu, Chen Chen, and Felicity Y. Han. "Progress in oral insulin delivery by PLGA nanoparticles for the management of diabetes." Drug Discovery Today (2022): 103393. https://www.sciencedirect.com/science/article/pii/S1359644622003865

“Highlights: Oral administration of insulin mimics the endogenous insulin secretion. Strategies for PLGA nanoparticles to overcome different barriers for oral insulin delivery are discussed. Challenges and future perspectives of PLGA nanoparticles for oral insulin delivery are also put forward. Abstract: Currently, the only practical way to treat type 1 and advanced insulin-dependent type 2 diabetes mellitus (T1/2DM) is the frequent subcutaneous injection of insulin, which is significantly different physiologically from endogenous insulin secretion from pancreatic islets and can lead to hyperinsulinemia, pain, and infection in patients with poor compliance. Hence, oral insulin delivery has been actively pursued to revolutionize the treatment of insulin-dependent diabetes. In this review, we provide an overview of recent progress in developing poly(lactic co-glycolic acid) (PLGA) nanoparticles (NPs) for oral insulin delivery. Different strategies for insulin-loaded PLGA NPs to achieve normoglycemic effects are discussed. Finally, challenges and future perspectives of PLGA NPs for oral insulin delivery are put forward. Keywords: oral insulin poly(lactic co-glycolic acid) (PLGA) biological barriers mucus epithelium gastrointestinal tract (GIT)”


Discoidal PLGA particles used for delivery of nintedanib in development of therapy for pulmonary fibrosis (lung-scarring)

Tuesday, October 11, 2022, 2:23 PM ET



Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease in which scar tissue forms along the inner lining of the lung preventing oxygen uptake. Recently, researchers at Yonsei University (Korea) used PLGAs (AP040, AP091, AP259) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to create disc-shaped nanoparticles. These were tested for use in treatment of lung-scarring. This research holds promise to improve treatment of this lethal disease. Read More: Park, S., J. Y. Park, J. H. Nahm, G. Kim, Y. L. Cho, W. J. Kang, and J. Key. "Systemic delivery of nintedanib using PLGA-based discoidal polymeric particles for idiopathic pulmonary fibrosis treatment." Materials Today Chemistry 26 (2022): 101181. https://www.sciencedirect.com/science/article/pii/S2468519422004104

“Highlights: Fabricated biodegradable discoidal polymeric particles containing nintedanib. Stability was improved by increasing the lactide/glycolide ratio of PLGA. Nintedanib-loaded PLGA-DPPs significantly reduced severity of pulmonary fibrosis. Nib-PLGA-DPPs have potential for improving the bioavailability of anti-fibrotic drugs. Abstract: Nintedanib is an approved tyrosine kinase inhibitor for the treatment of idiopathic pulmonary fibrosis (IPF); however, the bioavailability is low due to low solubility. In this study, nintedanib-loaded poly (lactic-co-glycolic acid)-based discoidal polymeric particles (Nib-PLGA-DPPs) were prepared, and their effectiveness was evaluated for the treatment of IPF. Nib-PLGA-DPPs with a uniform size and shape were manufactured using a top-down method by adjusting the lactide:glycolide molar ratio (50:50, 75:25, and 85:15) of PLGA. The physicochemical properties, drug loading content, and in vitro nintedanib release behavior were characterized; ex vivo biodistribution was performed in mice. The therapeutic efficacy of Nib-PLGA-DPPs was evaluated in a murine model of IPF induced by bleomycin (BLM). The synthesized Nib-PLGA-DPP showed an average size of 2.8 ± 0.2 μm with a zeta potential value of approximately −23.5 mV and 15.7% drug loading content. Approximately 40% of the nintedanib was initially released from Nib-PLGA (50:50)-DPPs during the first 24 h; however, the initial burst was significantly reduced to 18% by increasing the lactide:glycolide ratio from 50:50 to 85:15. Nib-PLGA (50:50)-DPPs showed rapid nintedanib release reaching completion within 3 days; however, Nib-PLGA (85:15)-DPPs sustained drug release over 7 days. Notably, ex vivo imaging showed that lung accumulation of fluorescent-labeled PLGA-DPPs in BLM-treated mice was approximately 2-fold higher than that in normal mice at early time points. In the IPF murine model, Nib-PLGA-DPPs showed a greater reduction in the total BALF cell numbers and severity of pulmonary fibrosis than nintedanib alone. In addition, the higher lactide content of the PLGA polymer exhibited a lower degree of pulmonary inflammation and fibrosis. Our findings indicate that the lactide ratio of the PLGA composition could enhance the bioavailability of drug molecules and that micro sized Nib-PLGA-DPPs could be a promising systemic delivery vehicle for treating IPF. Keywords: Idiopathic pulmonary fibrosis Nintedanib Discoidal polymeric particles PLGA Therapeutic efficacy”


PLA from PolySciTech used in testing on carboxylesterases from environmental sources for industrial applications

Wednesday, September 28, 2022, 4:51 PM ET



High-temperature-active microbial enzymes are important biocatalysts for many industrial applications including recycling of synthetic and biobased polyesters increasingly used in textiles, fibres, coatings and adhesives. Recently, researchers from Bangor University, Institute of Catalysis, University of Toronto, University of Calgary, Russian Academy of Sciences, and Institute of Polar Sciences used Poly(D)lactide (cat# AP159), Poly(L)lactide (Cat# AP128) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to test the ability these enzymes to break down various polymers. This research holds promise to provide for industrial enzymes for a wide array of applications. Read more: Distaso, Marco A., Tatyana N. Chernikova, Rafael Bargiela, Cristina Coscoln, Peter J. Stogios, Jose L. Gonzalez, Sofia Lemak et al. "Thermophilic carboxylesterases from hydrothermal vents of the volcanic island of Ischia active on synthetic and biobased polymers and mycotoxins." bioRxiv (2022). (https://www.biorxiv.org/content/10.1101/2022.09.17.508236v1.full.pdf)

“Hydrothermal vents have a widespread geographical distribution and are of high interest for investigating microbial communities and robust enzymes for various industrial applications. We examined microbial communities and carboxylesterases of two terrestrial hydrothermal vents of the volcanic island of Ischia (Italy) predominantly composed of Firmicutes (Geobacillus and Brevibacillus spp.), Proteobacteria and Bacteroidota. High-temperature enrichment cultures with the polyester plastics polyhydroxybutyrate (PHB) and polylactic acid (PLA) resulted in an increase of Thermus and Geobacillus spp., and to some extent, Fontimonas and Schleiferia spp. The screening at 37-70°C of metagenomic fosmid library from above enrichment cultures resulted in identification and successful production in Escherichia coli of three hydrolases (IS10, IS11 and IS12), all derived from yet uncultured Chloroflexota and showing low sequence identity (33-56%) to characterized enzymes. Enzymes exhibited maximal esterase activity at temperatures 70-90°C, with IS11 showing the highest thermostability (90% activity after 20 min incubation at 80°C). IS10 and IS12 were highly substrate-promiscuous and hydrolysed all 51 monoester substrates tested. Enzymes were active with polyesters (PLA and polyethylene terephthalate model substrate, 3PET) and mycotoxin T-2 (IS12). IS10 and IS12 had a classical α/β hydrolase core domain with a serine hydrolase catalytic triad (Ser155, His280, and Asp250) in the hydrophobic active sites. The crystal structure of IS11 resolved at 2.92 Å revealed the presence of the N-terminal β-lactamase-like domain and C-terminal lipocalin domain. The catalytic cleft of IS11 includes catalytic residues Ser68, Lys71, Tyr160, and Asn162, whereas the lipocalin domain encloses the catalytic cleft like a lid contributing to substrate binding. Thus, this study has identified novel thermotolerant carboxylesterases with a broad substrate range including polyesters and mycotoxins for potential applications in biotechnology.”


PLGA from PolySciTech used in development of nanoparticles for plasmid DNA delivery

Wednesday, September 28, 2022, 9:42 AM ET



The ability to transfect DNA into cells holds promise to provide for a wide array of uses in both therapeutic and biomedical applications. Recently, researchers at University of Newcastle (Australia) used PLGA (cat# AP041) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to create nanoparticles which were coated with cationic lipids and PEG-DSPE and utilized these for delivery of DNA. This research holds promise to improve clinical translation of DNA delivery techniques. Santhanes, Diviya, Alex Wilkins, Huiming Zhang, Robert John Aitken, and Mingtao Liang. "Microfluidic formulation of lipid/polymer hybrid nanoparticles for plasmid DNA (pDNA) delivery." International Journal of Pharmaceutics (2022): 122223. https://www.sciencedirect.com/science/article/pii/S0378517322007773

“Abstract: Lipid/polymer hybrid nanoparticles loaded with red fluorescent protein (RFP) encoded plasmid DNA (pDNA) was formulated using poly-lactic-co-glycolic acid (PLGA), cationic lipid DC-cholesterol and surfactant mPEG2000- DSPE. A lipid/ polymer ratio of 1: 10 at 1 mg/ mL surfactant concentration was found to be optimal for producing nanoparticles with diameters of 100- 120 nm that remained stable upon ultracentrifugation. The production of lipid/ polymer hybrid nanoparticles was investigated using microfluidics with a toroidal mixer design. Our results showed that the flow parameters significantly influenced the physicochemical characteristics of nanoparticles and loading of pDNA was only achieved at flow rate ratio (FRR) of 3: 1. The pDNA associated with nanoparticles was demonstrated to be structurally intact using gel electrophoresis, and the encapsulation efficiency (EE) was measured to be ∼65%. The prepared hybrid nanoparticles resulted in 20% of transfection efficacy in human embryonic kidney cells (HEK293T). This study demonstrated the potential of microfluidics in the development of hybrid nanoparticles for pDNA delivery, thus facilitating the clinical translation of DNA therapeutics.”


FDA-Akina joint publication describes solvent-vapor particle-morphological testing methodology for microstructural analysis

Tuesday, September 20, 2022, 10:14 AM ET




Long-Acting Injectable (LAI) delivery microparticles are complicated structures comprised of both biodegradable polymers, pharmaceutical compounds, and other excipients in a specific configuration so as to achieve the desired delivery profile. These allow for single injections to provide patients with the quantity of drug necessary for pharmaceutical efficacy from weeks up to six-months based on the formulation. Accomplishing this is not a trivial task and, due to their small size, obtaining critical information regarding the nature of the microstructural arrangement of the various components within the particles. To do this, the various components must be selectively altered or removed and the particle analyzed in order to record the change. Recently, Akina’s lab, in cooperation with the Food and Drug Administration via the GDUFA program, developed a methodology to selectively expose particles to semi-solvent vapors and record their changes. This methodology can enable learning more about the structural arrangements within microparticle formulations. Want to learn more about your prototype particles, see more about this and other analysis options here (http://www.akinalytics.com/index.php#home). Read more: Garner, John, Sarah Skidmore, Justin Hadar, Haesun Park, Kinam Park, Bin Qin, and Yan Wang. "Surface analysis of sequential semi-solvent vapor impact (SAVI) for studying microstructural arrangements of poly (lactide-co-glycolide) microparticles." Journal of Controlled Release 350 (2022): 600-612. http://kinampark.com/KPYear/files/2022%20Garner%2C%20Surface%20analysis%20of%20sequential%20semi-solvent%20vapor%20impact%20%28SAVI%29%20for%20studying%20microstructural%20arrangements%20of%20poly%28lactide-co-glycolide%29%20microparticles.pdf

“Abstract: Biodegradable poly(lactide-co-glycolide) (PLGA) microparticles have been used as long-acting injectable (LAI) drug delivery systems for more than three decades. Despite extensive use, few tools have been available to examine and compare the three-dimensional (3D) structures of microparticles prepared using different compositions and processing parameters, all collectively affecting drug release kinetics. Surface analysis after sequential semi-solvent impact (SASSI) was conducted by exposing PLGA microparticles to different semi-solvent in the liquid phase. The use of semi-solvent liquids presented practical experimental difficulties, particularly in observing the same microparticles before and after exposure to semi-solvents. The difficulties were overcome by using a new sequential semi-solvent vapor (SSV) method to examine the morphological changes of the same microparticles. The SASSI method based on SSV is called surface analysis of semi-solvent vapor impact (SAVI). Semi-solvents are the solvents that dissolve PLGA polymers depending on the polymer's lactide:glycolide (L:G) ratio. A sequence of semi-solvents was used to dissolve portions of PLGA microparticles in an L:G ratio-dependent manner, thus revealing different structures depending on how microparticles were prepared. Exposing PLGA microparticles to semi-solvents in the vapor phase demonstrated significant advantages over using semi-solvents in the liquid phase, such as in control of exposure conditions, access to imaging, decreasing the time for sequential exposure of semi-solvents, and using the same microparticles. The SSV approach for morphological analysis provides another tool to enhance our understanding of the microstructural arrangement of PLGA polymers. It will improve our comprehensive understanding of the factors controlling drug release from LAI formulations based on PLGA polymers. (This work was supported by BAA Contract # 75F40119C10096 from the U.S. Food and Drug Administration (FDA). The content is solely the responsibility of the authors and does not necessarily represent the official views of the FDA)”


Polymers from PolySciTech used in study on nanoparticle control by solvent-based nanoprecipitation

Thursday, September 15, 2022, 4:36 PM ET



Nanoparticles are generated by carefully controlling the precipitation of a polymer in a non-solvent condition. The choice of solvents and control of their interactions has a strong impact on nanoparticle size and properties however this has not received as much systematic study as it deserves. Recently, researchers from ETH Zurich utilized mPEG-PDLLa (AK056), mPEG-PLGA (AK037), mPEG-PCL (AK128) from PolySciTech Division of Akina, Inc. (www.polyscitech.com). Read more: Bovone, Giovanni, Lucien Cousin, Fabian Steiner, and Mark W. Tibbitt. "Solvent Controls Nanoparticle Size during Nanoprecipitation by Limiting Block Copolymer Assembly." Macromolecules (2022). https://pubs.acs.org/doi/abs/10.1021/acs.macromol.2c00907

“Abstract: Control of the properties of nanoparticles (NPs), including size, is critical for their application in biomedicine and engineering. Polymeric NPs are commonly produced by nanoprecipitation, where a solvent containing a block copolymer is mixed rapidly with a nonsolvent, such as water. Empirical evidence suggests that the choice of solvent influences NP size; yet, the specific mechanism remains unclear. Here, we show that solvent controls NP size by limiting block copolymer assembly. In the initial stages of mixing, polymers assemble into dynamic aggregates that grow via polymer exchange. At later stages of mixing, further growth is prevented beyond a solvent-specific water fraction. Thus, the solvent sets NP size by controlling the extent of dynamic growth up to growth arrest. An a priori model based on spinodal decomposition corroborates our proposed mechanism, explaining how size scales with the solvent-dependent critical water fraction of growth arrest and enabling more efficient NP engineering.”


Fluorescently-labelled PLGA from PolySciTech used in development of siRNA delivery spheroplexes for ulcerative colitis treatment

Friday, September 9, 2022, 10:10 AM ET



siRNA is short snippets of RNA that bind to transcribed messenger RNA and prevent it from being translated into a protein. This allows siRNA to “silence” select genetic expression and prevent the formation of proteins which may be pathological in nature. Recently, researchers at Universidade Federal de Minas Gerais (Brazil), PSL University, Sorbonne Université, Université de Lyon, and INSERM (France), used fluorescent PLGA-FPR648 (cat# AV008) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to create siRNA loaded spheroplexes. The Fluorescent polymer allowed for tracking of the nanoparticles for research applications. This research holds promise to improve siRNA delivery for gene therapy as ulcerative colitis treatment. Read More: Arruda, D.C., Lachagès, A.M., Demory, H., Escriou, G., Lai-Kuen, R., Dugas, P.Y., Hoffmann, C., Bessoles, S., Sarrabayrouse, G., Malachias, A. and Finet, S., 2022. Spheroplexes: Hybrid PLGA-cationic lipid nanoparticles, for in vitro and oral delivery of siRNA. Journal of Controlled Release, 350, pp.228-243. https://www.sciencedirect.com/science/article/pii/S0168365922005351


“Highlights: Spheroplexes (Sphx) were developed by a modified nanoprecipitation method using siRNA lipoplexes as starting nanoparticles. Sphx were spherical nanoparticles with surface characteristics similar to those of lipoplexes. Sphx were very stable particles and more efficient than siRNA lipoplexes for the in vitro delivery of siRNA. Sphx were uptake by macrophages/monocytes at the colon with nearly no toxicity after oral administration. The oral delivery of TNF-α siRNAs Sphx to mice with ulcerative colitis reduced the level of TNF-α and signs of lesions. Abstract: Vectorized small interfering RNAs (siRNAs) are widely used to induce gene silencing. Among the delivery systems used, lipid-based particles are the most effective. Our objective was the development of novel lipid-polymer hybrid nanoparticles, from lipoplexes (complexes of cationic lipid and siRNAs), and poly (lactic-co-glycolic acid) (PLGA), using a simple modified nanoprecipitation method. Due to their morphology, we called these hybrid nanoparticles Spheroplexes. We elucidated their structure using several physico-chemical techniques and showed that they are composed of a hydrophobic PLGA matrix, surrounded by a lipid envelope adopting a lamellar structure, in which the siRNA is complexed, and they retain surface characteristics identical to the starting nanoparticles, i.e. lipoplexes siRNA. We analyzed the composition of the particle population and determined the final percentage of spheroplexes within this population, 80 to 85% depending on the preparation conditions, using fluorescent markers and the ability of flow cytometry to detect nanometric particles (approximately 200 nm). Finally, we showed that spheroplexes are very stable particles and more efficient than siRNA lipoplexes for the delivery of siRNA to cultured cells. We administered spheroplexes contain siRNAs targeting TNF-α to mice with ulcerative colitis induced by dextran sulfate and our results indicate a disease regression effect with a response probably mediated by their uptake by macrophages / monocytes at the level of lamina propria of the colon. The efficacy of decreased level of TNF-α in vivo seemed to be an association of spheroplexes polymer-lipid composition and the specific siRNA. These results demonstrate that spheroplexes are a promising hybrid nanoparticle for the oral delivery of siRNA to the colon. Keywords: RNA interference Lipoplexes Hybrid nanoparticle Delivery system Biodegradable polymer Oral delivery”


PLA and PCL from PolySciTech used in development of opioid abuse deterrent system to prevent smoking of thebaine

Friday, September 9, 2022, 10:09 AM ET





Opioids provide for pain relief however, due to narcotic and addictive effects, are widely misused and abused. Systems which discourage misuse of opioids by seeking alternate routes of intake (i.e. smoking or injecting components from pills that are meant to be injested) than the prescribed method can reduce opportunites for misuse. Recently, Researchers at Purdue University used PLA (cat# AP006) and PCL (cat# AP257) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to create a microsphere formulation to combine in with oral doses of opioids which make smoking the tablets impractical. Read more: Vasiukhina, Anastasiia, Sheryhan F. Gad, Elyssia N. Wellington, Danielle M. Wilmes, Yoon Yeo, and Luis Solorio. "PLA-PCL Microsphere Formulation to Deter Abuse of Prescription Opioids by Smoking." International Journal of Pharmaceutics (2022): 122151. https://www.sciencedirect.com/science/article/pii/S0378517322007050

“Abstract: Opioids are commonly prescribed across the United States (US) for pain relief, despite their highly addictive nature that often leads to abuse and overdose deaths. Abuse deterrent formulations (ADFs) for prescription opioids make the non-therapeutic use of these drugs more difficult and less satisfying. Although approximately one-third of surveyed abusers in the US reported smoking opioids, to our knowledge, no commercialized ADF effectively prevents opioid smoking. Here, we report a novel approach to deter smoking of a model prescription opioid drug, thebaine (THB), by using polymer blend microspheres (MS) comprising polylactic acid (PLA) and polycaprolactone (PCL). We utilized high-performance liquid chromatography (HPLC) and thermogravimetric analysis (TGA) to test the ability of PLA-PCL MS to limit the escape of vaporized THB. Additionally, we compared the abuse-deterrent potential of PLA-PCL MS to that of activated carbon (AC) and mesoporous silica (MPS), two materials with excellent drug-adsorbing properties. Our MS formulation was effective in reducing the amount of both active drug and thermal degradation products in the vapor generated upon heating of THB. These results support that PLA-PCL microspheres can be co-formulated in a tablet with common prescription opioids to deter their abuse via the smoking route.”


PLGA-PEG-COOH and from PolySciTech Division of Akina, Inc. used in development of sialyl targetted nanoparticles for gastric cancer treatment

Friday, September 9, 2022, 10:08 AM ET



Gastric cancer accounts for about 783,000 deaths each year (Rawla, 2019; Prz Gastroenterol. 2019; 14(1): 26–38.) and can be difficult to treat based on how the cancer has spread through the system. Recently, researchers at Universidade do Porto and CESPU-IUCS (Portugal) utilized PLGA-PEG-COOH (Cat# AI076) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to create sialyl targetting nanoparticles to attach to epithelial tumors such as those in gastric cancer. This research holds promise to improve therapies against this disease. Read more: Diniz, Francisca, Maria Azevedo, Flávia Sousa, Hugo Osório, Diana Campos, Paula Sampaio, Joana Gomes, Bruno Sarmento, and Celso A. Reis. "Polymeric Nanoparticles Targeting Sialyl-Tn in Gastric Cancer: A Live Tracking Under Flow Conditions." Materials Today Bio (2022): 100417. https://www.sciencedirect.com/science/article/pii/S2590006422002150

“Abstract: Drug delivery using nanoparticles (NPs) represents a potential approach for therapy in cancer, such gastric cancer (GC) due to their targeting ability and controlled release properties. The use of advanced nanosystems that deliver anti-cancer drugs specifically to tumor cells may strongly rely on the expression of cancer-associated targets. Glycans aberrantly expressed by cancer cells are attractive targets for such delivery strategy. Sialylated glycans, such as Sialyl-Tn (STn) are aberrantly expressed in several epithelial tumors, including GC, being a potential target for a delivery nanosystem. The aim of this study was the development of NPs surface-functionalized with a specific antibody targeting the STn glycan and further evaluate this nanosystem effectiveness regarding its specificity and recognition capacity. Our results showed that the NPs surface-functionalized with anti-STn antibody efficiently are recognized by cells displaying the cancer-associated STn antigen under static and live cell monitoring flow conditions. This uncovers the potential use of such NPs for drug delivery in cancer. However, flow exposure was disclosed as an important biomechanical parameter to be taken into consideration. Here we presented an innovative and successful methodology to live track the NPs targeting STn antigen under shear stress, simulating the physiological flow. We demonstrate that unspecific binding of NPs agglomerates did not occur under flow conditions, in contrast with static assays. This robust approach can be applied for in vitro drug studies, giving valuable insights for in vivo studies. Keywords: Polymeric nanoparticles Gastric cancer Sialyl-Tn antigen Microfluidics”


PEG-PLGA from PolySciTech used in development of oral peptide delivery system for anti-inflammatory applications

Wednesday, August 24, 2022, 9:14 AM ET



Typically, peptides (shorter versions of proteins) can not be readily delivered as an oral formulation such as tablet or solution because most peptides are destroyed in the stomach and have poor transportation across the intestinal lining. This is unfortunate as peptide-based drugs are quite effective against a range of disease states and opening up more routes of administration can improve their application range. Recently, researchers at The University of Queensland (Australia) utilized mPEG-PLGA (cat# AK026) from PolySciTech division of Akina (www.polyscitech.com) to develop nanoparticles for oral delivery of anti-inflammatory peptides. This research holds promise to improve therapeutic routes for peptide delivery. Read more: Xu, Weizhi, Vinod Kumar, Cedric S. Cui, Xaria X. Li, Andrew K. Whittaker, Zhi Ping Xu, Maree T. Smith, Trent M. Woodruff, and Felicity Y. Han. "Success in navigating hurdles to oral delivery of a bioactive peptide complement antagonist through use of nanoparticles to increase bioavailability and in vivo efficacy." Advanced Therapeutics (2022): 2200109. https://onlinelibrary.wiley.com/doi/abs/10.1002/adtp.202200109

“Abstract: Substantial preclinical data have validated cyclic hexapeptide, complement C5a receptor 1 antagonists (C5aRAs) that target immune cells as novel treatments for a range of inflammatory diseases which currently have limited effective treatment options. However, like most small-molecule peptides, their poor oral bioavailability and short circulation half-life are major hurdles that have limited their clinical translation. Here, a single emulsion technique was employed to produce poly(lactic-co-glycolic) acid (PLGA) nanoparticles (NPs) with exceptionally high peptide C5aRA (PMX205) loading efficiency (over 50%). Strikingly, the PMX205-NPs not only facilitated prolonged release of the encapsulated PMX205 but also dramatically increased its oral bioavailability (from ∼25% to ∼50%), and therapeutic potential (∼ 95% inhibition of C5a induced neutrophilia in mice and maintenance of neuroprotective barrier integrity). The enhanced in vivo pharmacological activity of PMX205 in the form of NPs opens an exciting opportunity for the clinical application of peptide C5aRAs and possibly other therapeutic peptides. Keywords: C5aR1 antagonists (C5aRAs); bioactive peptide; nanoparticles (NPs); poly(lactic-coglycolic) acid (PLGA); oral bioavailability; pharmacokinetics and blood-brain barrier.”


PLGA-PEG-COOH from PolySciTech used in development of monoclonal antibody delivery system for heart-disease treatment

Wednesday, August 17, 2022, 2:01 PM ET





Atherosclerosis (heart disease) is a common cause of death characterized by lesions which act to block blood flow through blood vessels in the heart. Part of the cause is overexpression of fibronectin components which lead to extensive remodeling and tissue ingrowth into the vessel lumen. Recently researchers at University of Genoa (Italy) and Universidade do Porto (Portugal) utilized (PLGA-PEG-COOH, Cat# AI076) from PolySciTech division of Akina (www.polyscitech.com) to develop nanoparticles for delivery of Bevacizumab labelled with immunouteroglobin for targeted delivery. This research holds promise to improve treatments of heart disease in the future. Read more: Atanasio, Giulia De Negri, Pier Francesco Ferrari, Ana Baião, Patrizia Perego, Bruno Sarmento, Domenico Palombo, and Roberta Campardelli. "Bevacizumab encapsulation into PLGA nanoparticles functionalized with immunouteroglobin-1 as an innovative delivery system for atherosclerosis." International Journal of Biological Macromolecules (2022). https://www.sciencedirect.com/science/article/pii/S0141813022017639

“Abstract: Atherosclerosis represents one of the main causes of death in the Western world. It is a multifactorial pathology characterized by lesions that reduce the lumen of the vessels causing serious clinical events. The extradomain-B of fibronectin is overexpressed during angiogenesis and in tissues undergoing growth and extensive remodeling, i.e., atherosclerotic plaque. Bevacizumab is a recombinant humanized monoclonal antibody that can play a role against the angiogenesis process reducing the risk associated with this process in atherosclerosis. In this work, an innovative drug delivery device for target delivery of bevacizumab to the atherosclerotic lesion is proposed. A production protocol for poly(lactic-co-glycolic acid)-polyethylene glycol nanoparticles loaded with bevacizumab and functionalized with immunouteroglobin-1 was designed. Once immunouteroglobin-functionalized nanoparticles were produced, they were characterized regarding morphology, mean diameter, ζ-potential, association and conjugation efficiencies, bevacizumab release profile both in phosphate buffered saline and in serum, bevacizumab stability after release, cytocompatibility, and hemocompatibility. Nanoparticle mean diameter was in the range of 217–265 nm, their surface charge was between −21 and − 8 mV, and the association and conjugation efficiency of about 76 and 59 %, respectively. Fourier transform infrared spectroscopy analysis confirmed the functionalization of their surface with immunouteroglobin-1. In vitro assays showed that the studied nanoparticles were cytocompatible, once in contact with human endothelial and murine macrophages cell line up to 72 h, and hemocompatible, once in contact with red blood cells, at different concentrations of encapsulated BEV (0.1, 1, 10, and 100 μgBEV/mL).”


PLGA-Cy5 labelled polymer from PolySciTech used in development of anti-inflammatory treatment of spinal cord injury

Wednesday, August 17, 2022, 2:00 PM ET




One of the problems post spinal-cord injury is that inflammation (swelling, etc.) complicates and prevents the healing process. Targetted delivery of MAPK-activated protein kinase-2 (MK2) inhibitor can reduce the damaging effects of this inflammation. Recently researchers at Houston Methodist Academic Institute utilized PLGA-CY5 fluorescent (Cat# AV034) polymer from PolySciTech division of Akina (www.polyscitech.com) to create fluorescent nanoparticles for tracking purposes. This research holds promise to improve therapeutic outcomes for cpinal cord injury and reduce the incidence of associated paralysis. Read more: Stigliano, Cinzia, Allison Frazier, and Philip J. Horner. "Modulation of Neuroinflammation Via Selective Nanoparticle‐Mediated Drug Delivery to Activated Microglia/Macrophages in Spinal Cord Injury." Advanced Therapeutics: 2200083. https://onlinelibrary.wiley.com/doi/abs/10.1002/adtp.202200083

“Abstract: Inflammation after spinal cord injury (SCI) is characterized by immune cell invasion and activation, combined with inflammatory mediator release that worsens outcomes following primary trauma. Effective therapies targeting neuroinflammation remain an unmet need, and modulation of the injury microenvironment to induce a comprehensive pro-regenerative response is an attractive therapeutic approach. Given its crucial role in cell stress and inflammation after SCI, we focused on the potential of pharmacologically targeting MAPK-activated protein kinase-2 (MK2) to modulate the response of microglia/macrophages after injury. We developed nanoparticles (NPs) containing an MK2 inhibitor for specific targeting of microglia/macrophages. NPs selectively targeted and modulated activated microglia/macrophages in vitro and in a rat model of SCI. NPs in the acute injury setting reduced the pro-inflammatory cytokine IL-6 and increased the anti-inflammatory cytokine IL-10. Importantly, NPs had a significant effect on microglia/macrophage distribution and accumulation, leading to an ∼65% reduction of immune cells around the injury. Lastly, microglia/macrophage populations with activated morphology were significantly reduced compared to resting or ramified cells around the lesion site. Our strategy exhibits potential therapeutic efficiency and specificity for local, pharmacologic manipulation of activated microglia/macrophages, and is a versatile tool to manage acute inflammation and glia plasticity after central nervous system trauma.”


These posts are syndicated from John Garner's blog at http://jgakinainc.blogspot.com/ where you can post a question or comment. (Load took 0.40036916732788 seconds)

 

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