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.


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PLGA from PolySciTech used in development of Donepezil-loaded drug-releasing hydrogel for Alzheimer’s treatment

Monday, September 21, 2020, 4:16 PM ET

Injectable hydrogels have the capacity to provide for creating a soft, biocompatible structure which can be put into a patient and used to deliver a wide array of drugs or provide a tissue scaffold for cell growth. Recently, researchers at Kangwon National University, Seoul National University (Korea), University of California-Los Angeles, and Terasaki Institute for Biomedical Innovation (California, USA) used PLGA (AP059) from PolySciTech (www.polyscitech.com) to create donepezil-loaded microparticles inside of a HA-DOPA injectable hydrogel. This research holds promise to provide for sustained drug delivery of this molecule as a treatment option for Alzheimer’s disease. Read more: Seo, Ji-Hye, Song Yi Lee, Sungyun Kim, Mingyu Yang, Da In Jeong, ChaeRim Hwang, Min-Hwan Kim et al. "Monopotassium phosphate-reinforced in situ forming injectable hyaluronic acid hydrogels for subcutaneous injection." International Journal of Biological Macromolecules (2020). https://www.sciencedirect.com/science/article/pii/S0141813020344500

“Highlights: Monopotassium phosphate-incorporated hyaluronic acid hydrogel was fabricated. Both incorporation of KH2PO4 and pH modulation were engaged for gel crosslinking. Sustained drug release and prolonged in vivo retention of hydrogel were observed. Abstract: Monopotassium phosphate and pH modulation-reinforced hydrogel based on hyaluronic acid (HA) grafted with dopamine (dopa) was fabricated as one of subcutaneous injection formulations of donepezil (DPZ). Both incorporation of KH2PO4 and pH adjustment finally attributed to tuning viscoelastic and biodegradable properties of hydrogel system. Appropriate gelation time for in situ gel formation, single syringe injectability, self-healing capability, and viscoelastic features were accomplished with the optimization of KH2PO4 concentration in hydrogel systems. DPZ base (as a poorly water soluble drug) was encapsulated in poly(lactic-co-glycolic acid) (PLGA) microsphere (MS) and it was further embedded in the hydrogel structure for sustained drug release. Biodegradability of designed KH2PO4-incorporated HA-dopa/DPZ MS hydrogel system was assessed by optical imaging and the remained gel weight of crosslinked HA-dopa hydrogel group was 3.4-fold higher than that of unmodified HA-dopa mixture group on day 14 (p < 0.05). Subcutaneous injection of KH2PO4-incorporated HA-dopa/DPZ MS hydrogel did not induce any severe systemic toxicities. All these data suggest that designed HA-dopa/DPZ MS hydrogel structure crosslinked by KH2PO4 incorporation and pH adjustment can be one of promising subcutaneous injection formulations for sustained drug delivery. Keywords: Catechol Crosslinking Hyaluronic acid Hydrogel Potassium phosphate”

Mal-PEG-PLGA from PolySciTech used in development of Dp44mT-Loaded cancer-targeting nanoparticles

Thursday, September 10, 2020, 4:36 PM ET

A major drawback of chemotherapeutics is they systemically affect the entire body leading to serious side effects. Recently, researchers at University of Houston used Mal-PEG-PLGA (AI020), PLGA (AP041), and PEG-PLGA (AK027) from PolySciTech (www.polyscitech.com) to create Dp44mT loaded nanoparticles for cancer treatment. This research holds promise to improve chemotherapy regimens. Read more: Holley, C. K., and S. Majd. "Examining the Anti-Tumor Activity of Dp44mT-Loaded Nanoparticles In Vitro." In 2020 42nd Annual International Conference of the IEEE Engineering in Medicine & Biology Society (EMBC), pp. 5029-5032. IEEE, 2020. https://ieeexplore.ieee.org/abstract/document/9176197/

“We have recently reported encapsulating an antitumor iron chelator, Dp44mT (Di-2-pyridylketone-4,4dimethyl-3-thiosemicarbazone), in nanoparticles (NPs) of poly(lactic-co-glycolic acid) (PLGA). In this paper, we examine the effectiveness of this nano-formulation, referred to as Dp44mT-NPs, against several cancer cell lines in vitro; specifically, we evaluate the cytotoxicity of this formulation in glioma (U87, U251), breast (MCF7), and colorectal (HT29) cancer cell lines. Cell viability results from treatment of glioma cells with Dp44mT-NPs for 24-72 hrs revealed that these NPs were highly toxic towards these malignant cells with very low IC 50 values (<100 nM). Although addition of a PEG (poly(ethylene glycol)) layer to the surface of NPs reduced their toxicity in glioma cells, they remained highly toxic towards these cells (IC 50 of 135-210 nM). Dp44mT-NPs were also toxic towards breast MCF7 and colorectal HT29 cells, but at higher dosages (IC 50 >1 µM) compared to glioma cells. Addition of PEG to these NPs, again lowered their toxicity in these cells. Varying the percentage of PEG on NPs resulted in changes in their cytotoxicity, highlighting the necessity of further optimization of this parameter. This study, overall, demonstrates the therapeutic potential of Dp44mT-NPs against different malignant cells, with particularly promising results in highly-aggressive glioma tumor cells.”

PLGA-PEG-PLGA Thermogel from PolySciTech used in testing epigenetic approach to treating cardiovascular disease

Thursday, September 10, 2020, 4:35 PM ET

Hyperplasia describes the regrowth of vascular tissue within a cardiovascular stent which acts to block off an artery even after it has been stented. Recently, researchers at The Ohio State University and University of Virginia used PLGA-PEG-PLGA (AK012) from PolySciTech (www.polyscitech.com) to form a Thermogel for delivery of various factors which prevent hyperplasia. This research holds promise to provide for improved therapies against cardiovascular disease. Read more: Huang, Yitao, Go Urabe, Mengxue Zhang, Jing Li, Hatice Gulcin Ozer, Bowen Wang, K. Craig Kent, and Lian-Wang Guo. "Nullifying epigenetic writer DOT1L attenuates neointimal hyperplasia." Atherosclerosis 308 (2020): 22-31. https://www.sciencedirect.com/science/article/pii/S0021915020302987

“Highlights: DOT1L and its catalytic products H3K79me2 and H3K79me3 increased due to injury in rat carotid arteries after angioplasty. Silencing DOT1L in vivo inhibited H3K79 methylation and diminished injury-induced intimal hyperplasia. Treatment with a DOT1L inhibitor reduced H3K79 methylation and intimal hyperplasia. Abstract: Background and aims: Histone methyltransferases are emerging targets for epigenetic therapy. DOT1L (disruptor of telomeric silencing 1-like) is the only known methylation writer at histone 3 lysine 79 (H3K79). It is little explored for intervention of cardiovascular disease. We investigated the role of DOT1L in neointimal hyperplasia (IH), a basic etiology of occlusive vascular diseases. Methods and results: IH was induced via balloon angioplasty in rat carotid arteries. DOT1L and its catalytic products H3K79me2 and H3K79me3 (immunostaining) increased by 4.69 ± 0.34, 2.38 ± 0.052, and 3.07 ± 0.27 fold, respectively, in injured (versus uninjured) carotid arteries at post-injury day 7. Dot1l silencing via shRNA-lentivirus infusion in injured arteries reduced DOT1L, H3K79me2, and IH at day 14 by 54.5%, 37.1%, and 76.5%, respectively. Moreover, perivascular administration of a DOT1L-selective inhibitor (EPZ5676) reduced H3K79me2, H3K79me3, and IH by 56.1%, 58.6%, and 39.9%, respectively. In addition, Dot1l silencing and its inhibition (with EPZ5676) in vivo in injured arteries boosted smooth muscle α-actin immunostaining; pretreatment of smooth muscle cells with EPZ5676 in vitro reduced pro-proliferative marker proteins, including proliferating cell nuclear antigen (PCNA) and cyclin-D1. Conclusions: While DOT1L is upregulated in angioplasty-injured rat carotid arteries, either its genetic silencing or pharmacological inhibition diminishes injury-induced IH. As such, this study presents a strong rationale for continued mechanistic and translational investigation into DOT1L targeting for treatment of (re)stenotic vascular conditions.”

Fluorescent PLA-CY5 from PolySciTech used as tracer in development of cell-mediated drug delivery

Thursday, September 10, 2020, 4:34 PM ET

A fundamental problem with nanoparticles is that they are small. Although this is the mode of their action it also presents the problem that they are difficult to image and track during their application. Recently, researchers at EPFL (Switzerland) used PLA-Cyanine 5 (AV032) from PolySciTech (www.polyscitech.com) to create fluorescently-labelled particles which could be easily visualized during their uptake. This research holds promise to improve drug-delivery methods. Read more: Thomsen, Tanja, Ahmed B. Ayoub, Demetri Psaltis, and Harm-Anton Klok. "Fluorescence-based and Fluorescent label-free Characterization of Polymer Nanoparticle Decorated T cells." Biomacromolecules (2020). https://pubs.acs.org/doi/abs/10.1021/acs.biomac.0c00969

“Abstract: Cells are attractive carriers for the transport and delivery of nanoparticulate cargo. The use of cell-based carriers allows to enhance control over the biodistribution of drug-loaded polymers and polymer nanoparticles. One key element in the development of cell-based delivery systems is the loading of the cell-based carrier with the nanoparticle cargo, which can be achieved either by internalization of the payload or by immobilization on the cell surface. The surface modification of cells with nanoparticles or the internalization of nanoparticles by cells is usually monitored with fluorescence-based techniques, such as flow cytometry and confocal microscopy. In spite of the widespread use of these techniques, the use of fluorescent labels also poses some risks and has several drawbacks. Fluorescent dyes may bleach, or leach from the nanoparticles or alter the physicochemical properties of nanoparticles and their interactions and uptake by cells. Using poly(D,L-lactic acid) nanoparticles that are loaded with Coumarin 6, BODIPY 493/503 or DiO dyes as a model system, this manuscript demonstrates that the use of physically entrapped fluorescent labels can lead to false negative or erroneous results. The use of nanoparticles that contain covalently tethered fluorescent dyes instead was found to provide a robust approach to monitor cell surface conjugation reactions and to quantitatively analyze nanoparticle-decorated cells. Finally, it is shown that optical diffraction tomography is an attractive, alternative technique for the characterization of nanoparticle-decorated cells, which obviates the need for fluorescent labels.”

Thermogelling PLGA-PEG-PLGA from PolySciTech used in development of cardiovascular gel

Thursday, September 10, 2020, 4:34 PM ET

Cardiovascular disease remains one of the leading causes of death. A popular treatment is angioplasty to widen a blocked artery however, it is common afterwards for the blood-vessel to regrow in and reduce the flow of blood through the vessel. Recently, researchers at The Ohio State University, University of Virginia, and University of Wisconsin–Madison used PLGA-PEG-PLGA (AK012) from PolySciTech (www.polyscitech.com) to create a gel for delivery of medicinal molecules to reduce restenosis. Read more: Wang, Bowen, Mengxue Zhang, Go Urabe, Takuro Shirasu, Lian-Wang Guo, and K. Craig Kent. "PERK Inhibition Promotes Post-angioplasty Re-endothelialization via Modulating SMC Phenotype Changes." Journal of Surgical Research 257: 294-305. https://www.sciencedirect.com/science/article/pii/S0022480420303450

“Abstract: Background: Drug-eluting stents impair post-angioplasty re-endothelialization thus compromising restenosis prevention while heightening thrombotic risks. We recently found that inhibition of protein kinase RNA-like endoplasmic reticulum kinase (PERK) effectively mitigated both restenosis and thrombosis in rodent models. This motivated us to determine how PERK inhibition impacts re-endothelialization. Methods: Re-endothelialization was evaluated in endothelial-denuded rat carotid arteries after balloon angioplasty and periadventitial administration of PERK inhibitor in a hydrogel. To study whether PERK in smooth muscle cells (SMCs) regulates re-endothelialization by paracrinally influencing endothelial cells (ECs), denuded arteries exposing SMCs were lentiviral-infected to silence PERK; in vitro, the extracellular vesicles isolated from the medium of PDGF-activated, PERK-upregulating human primary SMCs were transferred to human primary ECs. Results: Treatment with PERK inhibitor versus vehicle control accelerated re-endothelialization in denuded arteries. PERK-specific silencing in the denuded arterial wall (mainly SMCs) also enhanced re-endothelialization compared to scrambled shRNA control. In vitro, while medium transfer from PDGF-activated SMCs impaired EC viability and increased the mRNA levels of dysfunctional EC markers, either PERK inhibition or silencing in donor SMCs mitigated these EC changes. Furthermore, CXCL10, a paracrine cytokine detrimental to ECs, was increased by PDGF activation and decreased after PERK inhibition or silencing in SMCs. Conclusions: Attenuating PERK activity pharmacologically or genetically provides an approach to accelerating post-angioplasty re-endothelialization in rats. The mechanism may involve paracrine factors regulated by PERK in SMCs that impact neighboring ECs. This study rationalizes future development of PERK-targeted endothelium-friendly vascular interventions. Keywords: Re-endothelialization Angioplasty Smooth muscle cell Endothelial cell PERK”

PLGA from PolySciTech used in development of anti-MRSA nanoparticles

Thursday, September 10, 2020, 4:33 PM ET

Bacterial infections in bone tissue are extremely difficult to treat even with extensive antibiotic therapy as drug transport into these hard to reach areas is minimal. Recently, researchers at Temple University (Philadelphia, PA) used PLGA (AP063) to create rifampicin loaded nanoparticles to treat MRSA bone infections. This research holds promise to reduce morbidity associated with these conditions. Read More: Guo, Pengbo, Hui Yi Xue, Bettina A. Buttaro, Ngoc T. Tran, and Ho Lun Wong. "Enhanced eradication of intracellular and biofilm-residing methicillin-resistant Staphylococcus aureus (MRSA) reservoirs with hybrid nanoparticles delivering rifampicin." International Journal of Pharmaceutics (2020): 119784. https://www.sciencedirect.com/science/article/pii/S0378517320307699

“Abstract: Osteomyelitis carries a high risk of recurrence even after extended, aggressive antibiotic therapy. One of the key challenges is to eradicate the reservoirs of methicillin-resistant Staphylococcus aureus (MRSA) inside the host bone cells and their biofilms. Our goal is to develop rifampicin loaded lipid-polymer hybrid nanocarriers (Rf-LPN) and evaluate if they can achieve enhanced rifampicin delivery to eradicate these intracellular and biofilm-residing MRSA. After optimization of the composition, Rf-LPN demonstrated size around 110 nm in diameter that remained stable in serum-supplemented medium, drug payload up to 11.7% and sustained rifampicin release for 2 weeks. When comparing Rf-LPN with free rifampicin, moderate but significant (p < 0.05) improvement of the activities against three osteomyelitis-causing bacteria (USA300-0114, CDC-587, RP-62A) in planktonic form were observed. In comparison, the enhancements in the activities against the biofilms and intracellular MRSA by Rf-LPN were even more substantial. The MBEC50 values against USA300-0114, CDC-587, and RP-62A were 42 vs 155, 70 vs 388, and 265 ng/ml vs over 400 ng/ml, respectively, and up to 18.5-fold reduction in the intracellular MRSA counts in osteoblasts was obtained. Confocal microscope images confirmed extensive accumulation of Rf-LPN inside the biofilm matrix and MRSA-infected osteoblasts. Overall, in this proof-of-concept study we have developed and validated the strategy to exploit the nanoparticle-cell and nanoparticle-biofilm interactions with a new rifampicin nanoformulation for prevention of osteomyelitis recurrence and chronicity caused by the elusive MRSA. Keywords: Nanoparticles Antibiotic Rifampicin MRSA Osteomyelitis.”

PLGA and PLGA-Rhodamine from PolySciTech used in the development of antibacterial nanoparticles

Tuesday, September 1, 2020, 4:53 PM ET

On the scale of micro structures the human cell is quite large and can easily be entered by viral replicates and bacteria. Once inside the cell, pathogens are very difficult to treat. Recently, researchers at Purdue University, Assiut University (Egypt), and China Medical University (China) used PLGA (AP020) and PLGA-Rhodamine (AV011) from PolySciTech (www.polyscitech.com) to develop silver-pexiganan loaded nanoparticles designed to target bacteria even inside of cells. This research holds promise to improve therapies against intracellular bacteria which are resistant to antibiotics. Read more: Elnaggar, Marwa G., Kunyu Jiang, Hassan E. Eldesouky, Yihua Pei, Jinho Park, Simseok A. Yuk, Fanfei Meng et al. "Antibacterial nanotruffles for treatment of intracellular bacterial infection." Biomaterials (2020): 120344. https://www.sciencedirect.com/science/article/pii/S0142961220305901

“Abstract: Bacterial pathogens residing in host macrophages in intracellular infections are hard to eradicate because traditional antibiotics do not readily enter the cells or get eliminated via efflux pumps. To overcome this challenge, we developed a new particle formulation with a size amenable to selective macrophage uptake, loaded with two antibacterial agents - pexiganan and silver (Ag) nanoparticles. Here, pexiganan was loaded in 600 nm poly(lactic-co-glycolic acid) (PLGA) particles (NP), and the particle surface was modified with an iron-tannic acid supramolecular complex (pTA) that help attach Ag nanoparticles. PLGA particles coated with Ag (NP-pTA-Ag) were taken up by macrophages but not by non-phagocytic cells, such as fibroblasts, reducing non-specific toxicity associated with Ag nanoparticles. NP-pTA-Ag loaded with pexiganan (Pex@NP-pTA-Ag) showed more potent antibacterial activity against various intracellular pathogens than NP-pTA-Ag or Pex@NP (pexiganan-loaded NP with no Ag), suggesting a collaborative function between pexiganan and Ag nanoparticles. Mouse whole-body imaging demonstrated that, upon intravenous injection, NP-pTA-Ag quickly accumulated in the liver and spleen, where intracellular bacteria tend to reside. These results support that Pex@NP-pTA-Ag is a promising strategy for the treatment of intracellular bacterial infection. Keywords: Intracellular infection Pexiganan Silver nanoparticles Macrophages Intracellular drug delivery”

PLGA-PEG-Biotin from PolySciTech used in development of lutein loaded nanoparticle for macular degeneration treatment

Tuesday, September 1, 2020, 4:52 PM ET

Macular Degeneration is a progressive disease in which a small central portion of the retina wears down over time. Lutein is a carotenoid with reported anti-inflammatory properties which can improve macular degeneration but has relatively poor absorption/transport. Recently, researchers at High Point University, University of Missouri, and University of the Sciences in Philadelphia used PLGA (AP041) and PLGA-PEG-Biotin (AI167) from PolySciTech (www.polyscitech.com) to create nanoparticles for treating ocular disease. This research holds promise to improve treatments against this blinding disease in the future. Read more: Bolla, Pradeep Kumar, Vrinda Gote, Mahima Singh, Manan Patel, Bradley A. Clark, and Jwala Renukuntla. "Lutein-Loaded, Biotin-Decorated Polymeric Nanoparticles Enhance Lutein Uptake in Retinal Cells." Pharmaceutics 12, no. 9 (2020): 798. https://www.mdpi.com/1999-4923/12/9/798

“Age related macular degeneration (AMD) is one of the leading causes of visual loss and is responsible for approximately 9% of global blindness. It is a progressive eye disorder seen in elderly people (>65 years) mainly affecting the macula. Lutein, a carotenoid, is an antioxidant, and has shown neuroprotective properties in the retina. However, lutein has poor bioavailability owing to poor aqueous solubility. Drug delivery to the posterior segment of the eye is challenging due to the blood–retina barrier. Retinal pigment epithelium (RPE) expresses the sodium-dependent multivitamin transporter (SMVT) transport system which selectively uptakes biotin by active transport. In this study, we aimed to enhance lutein uptake into retinal cells using PLGA–PEG–biotin nanoparticles. Lutein loaded polymeric nanoparticles were prepared using O/W solvent-evaporation method. Particle size and zeta potential (ZP) were determined using Malvern Zetasizer. Other characterizations included differential scanning calorimetry, FTIR, and in-vitro release studies. In-vitro uptake and cytotoxicity studies were conducted in ARPE-19 cells using flow cytometry and confocal microscopy. Lutein was successfully encapsulated into PLGA and PLGA–PEG–biotin nanoparticles (<250 nm) with uniform size distribution and high ZP. The entrapment efficiency of lutein was ≈56% and ≈75% for lutein-loaded PLGA and PLGA–PEG–biotin nanoparticles, respectively. FTIR and DSC confirmed encapsulation of lutein into nanoparticles. Cellular uptake studies in ARPE-19 cells confirmed a higher uptake of lutein with PLGA–PEG–biotin nanoparticles compared to PLGA nanoparticles and lutein alone. In vitro cytotoxicity results confirmed that the nanoparticles were safe, effective, and non-toxic. Findings from this study suggest that lutein-loaded PLGA–PEG–biotin nanoparticles can be potentially used for treatment of AMD for higher lutein uptake. Keywords: lutein; PLGA; PLGA–PEG–biotin; ARPE-19; retina; macular edema; age-related macular degeneration; biotin-decorated nanoparticles; polymeric nanoparticles; targeted therapy”

PLGA-PEG-Folate from PolySciTech used in development of lutein-based treatment of encephalopathy

Thursday, August 27, 2020, 4:52 PM ET

Hypoxic ischaemic encephalopathy is a limitation of oxygenated blood flow to the newborn’s brain during the birthing process which can lead to severe damage. Recently, researchers at The University of Texas El Paso, University of Missouri, University of the Science in Philadelphia, University of Utah, and Texas Tech University Used PLGA-PEG-Folate (AI168) to develop lutein delivery nanoparticle system. This research holds promise to improve the treatment of hypoxic ischaemic encephalopathy. Read more: Pradeep Kumar Bolla, Vrinda Gote, Mahima Singh, Venkata Kashyap Yellepeddi, Manan Patel, Dhananjay Pal, Xiaoming Gong, Devaraj Sambalingam & Jwala Renukuntla (2020) Preparation and characterization of lutein loaded folate conjugated polymeric nanoparticles, Journal of Microencapsulation, DOI: 10.1080/02652048.2020.1809724 https://www.tandfonline.com/doi/full/10.1080/02652048.2020.1809724

“Abstract: Aim: To prepare and characterise lutein-loaded polylactide-co-glycolide–polyethylene glycol–folate (PLGA-PEG-FOLATE) nanoparticles and evaluate enhanced uptake in SK-N-BE(2) cells. Methods: Nanoparticles were prepared using O/W emulsion solvent evaporation and characterised using DLS, SEM, DSC, FTIR and in-vitro release. Lutein-uptake in SK-N-BE(2) cells was determined using flow-cytometry, confocal-microscopy and HPLC. Control was lutein PLGA nanoparticles. Results: The size of lutein-loaded PLGA and PLGA-PEG-FOLATE nanoparticles were 189.6 ± 18.79 nm and 188.0 ± 4.06 nm, respectively. Lutein entrapment was ∼61%(w/w) and ∼73%(w/w) for PLGA and PLGA-PEG-FOLATE nanoparticles, respectively. DSC and FTIR confirmed encapsulation of lutein into nanoparticles. Cellular uptake studies showed ∼1.6 and ∼2-fold enhanced uptake of lutein from PLGA-PEG-FOLATE nanoparticles compared to PLGA nanoparticles and lutein, respectively. Cumulative release of lutein was higher in PLGA nanoparticles (100% (w/w) within 24 h) compared to PLGA-PEG-FOLATE nanoparticles (∼80% (w/w) in 48 h). Conclusion: Lutein-loaded PLGA-PEG-FOLATE nanoparticles could be a potential treatment for hypoxic ischaemic encephalopathy. Keywords: Lutein, PLGA-PEG-FOLATE, folate decorated nanoparticles, PLGA, perinatal asphyxia, hypoxic ischaemic encephalopathy, targeted delivery”

PLGA-PEG-N3 and PLGA-PEG-NHS from PolySciTech used in development of cancer-targeted nanoparticle system

Thursday, August 27, 2020, 4:51 PM ET

Antibody’s references a class of biochemicals which have the ability to attach to a specific antigen and the use of antibody-antigen conjugation allows for the development of cancer-targeted nanoparticles. Recently, researchers at Queen's University Belfast and University College London (United Kingdom) used PLGA-PEG-N3 (AI085) and PLGA-PEG-NHS (AI064) from PolySciTech (www.polyscitech.com) to create labelled nanoparticles for delivery to cancer. This research holds promise to improve chemotherapeutic efficacy in the future. Read More: Greene, Michelle, João CF Nogueira, Shannon R. Tracey, Daniel A. Richards, William McDaid, James F. Burrows, Katrina Campbell, Dan Longley, Vijay Chudasama, and Christopher J. Scott. "Refined construction of antibody-targeted nanoparticles leads to superior antigen binding and enhanced delivery of an entrapped payload to pancreatic cancer cells." Nanoscale (2020). https://pubs.rsc.org/en/content/articlehtml/2020/nr/d0nr02387f

“Antibody-targeted nanoparticles have shown exceptional promise as delivery vehicles for anticancer drugs, although manufacturability challenges have hampered clinical progress. These include the potential for uncontrolled and random antibody conjugation, resulting in masked or inactive paratopes and unwanted Fc domain interactions. To circumvent these issues, we show that the interchain disulfide of cetuximab F(ab) may be selectively re-bridged with a strained alkyne handle, to permit ‘click’ coupling to azide-capped nanoparticles in a highly uniform and oriented manner. When compared to conventional carbodiimide chemistry, this conjugation approach leads to the generation of nanoparticles with a higher surface loading of cetuximab F(ab) and with markedly improved ability to bind to the target epidermal growth factor receptor. Moreover, we show that entrapment of a camptothecin payload within these nanoparticles can enhance drug targeting to antigen-expressing pancreatic cancer cells, resulting in superior cytotoxicity versus the conventional nanoformulation. Collectively, this work highlights the critical need to develop refined methods for the construction of targeted nanoparticles that will accelerate their clinical translation through improved performance and manufacturability.”

PLGA from PolySciTech used in development of nanoparticle based melanoma treatment.

Thursday, August 27, 2020, 4:51 PM ET

Melanoma is a common and aggressive form of skin cancer. Recently, researchers at The University of Texas at Arlington used PLGA (AP040) from PolySciTech (www.polyscitech.com) to create Trametinib loaded nanoparticles for melanoma treatment. This research holds promise to provide for improved therapies against this and other forms of cancer. Read more: Yaman, Serkan, Harish Ramachandramoorthy, Gizem Oter, Daria Zhukova, Tam Nguyen, Manoj Kumar Sabnani, Jon A. Weidanz, and Kytai Truong Nguyen. "Melanoma Peptide MHC Specific TCR Expressing T-Cell Membrane Camouflaged PLGA Nanoparticles for Treatment of Melanoma Skin Cancer." Frontiers in Bioengineering and Biotechnology 8 (2020): 943. https://www.frontiersin.org/articles/10.3389/fbioe.2020.00943/pdf

“Melanoma is one of the most aggressive skin cancers, and the American Cancer Society reports that every hour, one person dies from melanoma. While there are a number of treatments currently available for melanoma (e.g., surgery, chemotherapy, immunotherapy, and radiation therapy), they face several problems including inadequate response rates, high toxicity, severe side effects due to non-specific targeting of anticancer drugs, and the development of multidrug resistance during prolonged treatment. To improve chemo-drug therapeutic efficiency and overcome these mentioned limitations, a multifunctional nanoparticle has been developed to effectively target and treat melanoma. Specifically, poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) were coated with a cellular membrane derived from the T cell hybridoma, 19LF6 endowed with a melanoma-specific anti-gp100/HLA-A2 T-cell receptor (TCR) and loaded with an FDA-approved melanoma chemotherapeutic drug Trametinib. T-cell membrane camouflaged Trametinib loaded PLGA NPs displayed high stability, hemo- and cyto-compatibility. They also demonstrated membrane coating dependent drug release profiles with the most sustained release from the NPs proportional with the highest amount of membrane used. 19LF6 membrane-coated NPs produced a threefold increase in cellular uptake toward the melanoma cell line in vitro compared to that of the bare nanoparticle. Moreover, the binding kinetics and cellular uptake of these particles were shown to be membrane/TCR concentration-dependent. The in vitro cancer killing efficiencies of these NPs were significantly higher compared to other NP groups and aligned with binding and uptake characteristics. Particles with the higher membrane content (greater anti-gp100 TCR content) were shown to be more effective when compared to the free drug and negative controls. In vivo biodistribution studies displayed the theragnostic capabilities of these NPs with more than a twofold increase in the tumor retention compared to the uncoated and non-specific membrane coated groups. Based on these studies, these T-cell membrane coated NPs emerge as a potential theragnostic carrier for imaging and therapy applications associated with melanoma.”

PLGA-NH2 from PolySciTech used in research tracking the fate of ingested PLGA nanoparticles

Tuesday, August 18, 2020, 12:02 PM ET

Although PLGA is known to break down into lactic and glycolic acid the exact rate of this degradation and what happens to these metabolic products still requires further understanding. Recently, researchers at Case Western Reserve University and Johns Hopkins University used PLGA-NH2 (AI010) from PolySciTech (www.polyscitech.com) to create PLGA-Europium-Cryptate as a tracer molecule to track the PLGA nanoparticles over the course of digestion. They found that the condition of the patient’s digestive system as it relates to their overall health (obesity, diabetes, etc.) can play a strong role in the fate of ingested PLGA nanoparticles. This research can improve outcomes and applications for developed PLGA nanoparticle formulations in the future. Read more: Chaplin, Alice, Huiyun Gao, Courteney Asase, Palanivel Rengasamy, Bongsoo Park, Danielle Skander, Gürkan Bebek, Sanjay Rajagopalan, and Andrei Maiseyeu. "Systemically-delivered biodegradable PLGA alters gut microbiota and induces transcriptomic reprogramming in the liver in an obesity mouse model." Scientific Reports 10, no. 1 (2020): 1-16. https://www.nature.com/articles/s41598-020-69745-x

“Biodegradable materials, including the widely used poly (lactic-co-glycolic acid) (PLGA) nanoparticles contained in slow-release drug formulations, scaffolds and implants, are ubiquitous in modern biomedicine and are considered inert or capable of being metabolized through intermediates such as lactate. However, in the presence of metabolic stress, such as in obesity, the resulting degradation products may play a detrimental role, which is still not well understood. We evaluated the effect of intravenously-administered PLGA nanoparticles on the gut-liver axis under conditions of caloric excess in C57BL/6 mice. Our results show that PLGA nanoparticles accumulate and cause gut acidification in the cecum, accompanied by significant changes in the microbiome, with a marked decrease of Firmicutes and Bacteroidetes. This was associated with transcriptomic reprogramming in the liver, with a downregulation of mitochondrial function, and an increase in key enzymatic, inflammation and cell activation pathways. No changes were observed in systemic inflammation. Metagenome analysis coupled with publicly available microarray data suggested a mechanism of impaired PLGA degradation and intestinal acidification confirming an important enterohepatic axis of metabolite-microbiome interaction resulting in maintenance of metabolic homeostasis. Thus, our results have important implications for the investigation of PLGA use in metabolically-compromised clinical and experimental settings.”

PCL and PLA from PolySciTech used in development of neural tissue regeneration scaffold.

Tuesday, August 18, 2020, 12:00 PM ET

Human cells can not grow into tissues without a scaffold or extra-cellular matrix to attach to. This limits the ability of damaged tissue to heal after injury or disease. Recently, researchers at Nanyang Technical University used PCL (AP257, AP260) and PLA (AP047, AP114) from PolySciTech (www.polyscitech.com) to create nanofiber meshes and evaluate their effect on myelination. This research holds promise to provide for improved treatment of damage in the central nervous system by providing a scaffold for cells to grow on. Read more: Ong, William, Nicolas Marinval, Junquan Lin, Mui Hoon Nai, Yee‐Song Chong, Coline Pinese, Sreedharan Sajikumar et al. "Biomimicking Fiber Platform with Tunable Stiffness to Study Mechanotransduction Reveals Stiffness Enhances Oligodendrocyte Differentiation but Impedes Myelination through YAP‐Dependent Regulation." Small (2020): 2003656. https://onlinelibrary.wiley.com/doi/abs/10.1002/smll.202003656

“A key hallmark of many diseases, especially those in the central nervous system (CNS), is the change in tissue stiffness due to inflammation and scarring. However, how such changes in microenvironment affect the regenerative process remains poorly understood. Here, a biomimicking fiber platform that provides independent variation of fiber structural and intrinsic stiffness is reported. To demonstrate the functionality of these constructs as a mechanotransduction study platform, these substrates are utilized as artificial axons and the effects of axon structural versus intrinsic stiffness on CNS myelination are independently analyzed. While studies have shown that substrate stiffness affects oligodendrocyte differentiation, the effects of mechanical stiffness on the final functional state of oligodendrocyte (i.e., myelination) has not been shown prior to this. Here, it is demonstrated that a stiff mechanical microenvironment impedes oligodendrocyte myelination, independently and distinctively from oligodendrocyte differentiation. Yes‐associated protein is identified to be involved in influencing oligodendrocyte myelination through mechanotransduction. The opposing effects on oligodendrocyte differentiation and myelination provide important implications for current work screening for promyelinating drugs, since these efforts have focused mainly on promoting oligodendrocyte differentiation. Thus, the platform may have considerable utility as part of a drug discovery program in identifying molecules that promote both differentiation and myelination.”

PLGA from PolySciTech used in development off Stamp-formed Microparticles for drug-delivery applications.

Tuesday, August 18, 2020, 12:00 PM ET

Medicinal molecules only have efficacy if they can be successfully transferred to the site of action. Recently, researchers at Massachusetts Institute of Technology, Rice University, and National Institutes of Health use PLGA (AP045) from PolySciTech (www.polyscitech.com) as part of their development of stamp-formed PLGA microparticles for drug delivery applications. This research holds promise to improve drug delivery for a variety of disease states including cancer. Read more: Lu, Xueguang, Lei Miao, Wenting Gao, Ziqi Chen, Kevin J. McHugh, Yehui Sun, Zachary Tochka et al. "Engineered PLGA microparticles for long-term, pulsatile release of STING agonist for cancer immunotherapy." Science Translational Medicine 12, no. 556 (2020). https://stm.sciencemag.org/content/12/556/eaaz6606.abstract

“Squaring away tumors: Cancer immunotherapy has been achieving increasing prominence in recent years, but many patients’ tumors still do not respond to existing immunotherapy modalities. One approach that offers promise is activation of the stimulator of interferon gene (STING) pathway, which can promote immune responses within the tumor microenvironment. STING agonists have shown promising results in mice and people, but they require multiple intratumoral injections, which are impractical for many tumors. Lu et al. designed box-shaped microparticles filled with STING agonist and optimized them to release the agonist at appropriate time intervals after being injected into a tumor just once, showing promising results in multiple mouse models of cancer. Activation of the stimulator of interferon gene (STING) pathway within the tumor microenvironment has been shown to generate a strong antitumor response. Although local administration of STING agonists has promise for cancer immunotherapy, the dosing regimen needed to achieve efficacy requires frequent intratumoral injections over months. Frequent dosing for cancer treatment is associated with poor patient adherence, with as high as 48% of patients failing to comply. Multiple intratumoral injections also disrupt the tumor microenvironment and vascular networks and therefore increase the risk of metastasis. Here, we developed microfabricated polylactic-co-glycolic acid (PLGA) particles that remain at the site of injection and release encapsulated STING agonist as a programmable sequence of pulses at predetermined time points that mimic multiple injections over days to weeks. A single intratumoral injection of STING agonist–loaded microparticles triggered potent local and systemic antitumor immune responses, inhibited tumor growth, and prolonged survival as effectively as multiple soluble doses, but with reduced metastasis in several mouse tumor models. STING agonist–loaded microparticles improved the response to immune checkpoint blockade therapy and substantially decreased the tumor recurrence rate from 100 to 25% in mouse models of melanoma when administered during surgical resection. In addition, we demonstrated the therapeutic efficacy of STING microparticles on an orthotopic pancreatic cancer model in mice that does not allow multiple intratumoral injections. These findings could directly benefit current STING agonist therapy by decreasing the number of injections, reducing risk of metastasis, and expanding its applicability to hard-to-reach cancers.”

PLGA-PEG-PLGA from PolySciTech used in Thermogel patent for ocular drug delivery

Tuesday, August 18, 2020, 11:59 AM ET

PLGA-PEG-PLGA can be used to generate a Thermogel for a wide variety of drug-delivery applications. Recently a patent was issued regarding the use of PolySciTech (www.polyscitech.com) product AK024 to deliver medicinal molecules in the ocular space. Read more: Sutariya, Vijaykumar Bhadabhai, Anjali A. Hirani, and Yashwant V. Pathak. "Nanoparticles in thermoreversible gels for enhanced therapeutics." U.S. Patent 10,729,663, issued August 4, 2020. http://www.freepatentsonline.com/10729663.html

“The present invention provides a sustained drug delivery system for the treatment of age-related macular degeneration (AMD), comprising corticosteroid encapsulated nanoparticles incorporated into a thermoreversible hydrogel. The corticosteroid may be triamcinolone acetate (TA), dexamethasone, or loteprednol etabonate (LE). The proposed drug delivery system is nontoxic to ARPE-19 (retinal pigment epithelium) cells and significantly reduces VEGF (vascular endothelial growth factor) expression as compared to solutions of the coticosteroids. The present invention provides sustained delivery of the corticosteroid to the posterior segment of the eye, reducing the frequency of intraocular injections necessary to maintain therapeutic concentrations.”

PEG-PLGA from PolySciTech used in development of daunorubicin nanoparticles for skin-cancer treatment

Wednesday, August 12, 2020, 1:56 PM ET

Treatment of cancer is complicated by lack of specificity for chemotherapeutic compounds against cancer leading to most of the promising drugs having side-effects that limit their usage. Combining chemotherapy with phototherapy, however, could provide for an improved combination treatment in which the two strategies are applied together. Recently, researchers at Warsaw University of Technology and Wrocław University of Science and Technology (Poland) used mPEG-PLGA (AK002) from PolySciTech (www.polyscitech.com) to create nanoparticles loaded with photosensitizer, IR-768, and chemotherapy agent, daunorubicin. This research holds promise to provide for improved therapies against cancer. Read more: Tokarska, Katarzyna, Łukasz Lamch, Beata Piechota, Kamil Żukowski, Michał Chudy, Kazimiera A. Wilk, and Zbigniew Brzózka. "Co-delivery of IR-768 and daunorubicin using mPEG-b-PLGA micelles for synergistic enhancement of combination therapy of melanoma." Journal of Photochemistry and Photobiology B: Biology (2020): 111981. https://www.sciencedirect.com/science/article/pii/S1011134420304310

“Malignant melanoma is an emerging problem worldwide due to the high degree of lethalness. Its aggressiveness and the ability to metastasize along with the heterogeneity at the molecular and cellular levels, limit the overall therapeutic efficacy. Despite significant advances in melanoma treatment over the last decade, there is still a need for improved therapeutic modalities. Thus, we demonstrate here a combinatorial approach that targets multiple independent therapeutic pathways, in which polymeric micelles (PMs) were used as efficacious colloidal nanocarriers loaded with both daunorubicin (DRB) as a cytotoxic drug and IR-768 as a photosensitizer. This afforded the dual drug loaded delivery system IR-768 + DRB in PMs. The fabricated mPEG-b-PLGA micelles (hydrodynamic diameters ≈ 25 nm) had a relatively narrow size distribution (PdI > ca. 0.3) with uniform spherical shapes. CLSM study showed that mPEG-b-PLGA micelles were uptaken by mitochondria, which further contributed to excellent singlet oxygen generation capacity for PDT in A375 melanoma cells. Furthermore, the PMs were efficiently internalized by tested cells through endocytosis, resulting in much higher cellular uptake comparing to the free drug. As a result of these properties, IR-768 + DRB in PMs exhibited very potent and synergistically enhanced anticancer activity against A375 cells. Additionally, this combination approach allowed to reduce drug doses and provided low side effects towards normal HaCaT. This study indicates excellent properties of mPEG-b-PLGA micelles resulting in great therapeutic potential possessed by the developed nanoscale drug delivery system for combined chemo-photodynamic therapy of melanoma. Keywords: Co-encapsulation Polymeric micelles Combination therapy Photodynamic therapy Melanoma Nanoscale drug delivery systems”

PLGA-PEG-Mal from PolySciTech used in development of oral insulin delivery system

Wednesday, August 12, 2020, 1:33 PM ET

Diabetes is a common and debilitating disease caused by inappropriate concentration of glucose in the blood stream. It is often treated using insulin however insulin must typically be injected which is painful and unpleasant leading to poor patient compliance. Recently, researchers at University of Porto (Portugal) and Oslo University (Norway) used PLGA-PEG-Mal (AI110) from PolySciTech (www.polyscitech.com) to create labeled nanoparticles. These particles were loaded with insulin and tested in animal model for absorption. This research holds promise for improved therapies against diabetes in the future. Read more: Azevedo, Cláudia, Jeannette Nilsen, Algirdas Grevys, Rute Nunes, Jan Terje Andersen, and Bruno Sarmento. "Engineered albumin-functionalized nanoparticles for improved FcRn binding enhance oral delivery of insulin." Journal of Controlled Release (2020). https://www.sciencedirect.com/science/article/pii/S0168365920304363

“Abstract: Oral delivery of biopharmaceuticals, as insulin, is hampered by rapid degradation and inefficient absorption in the gastrointestinal tract (GIT). To solve this, a new class of biodegradable poly(lactic-co-glycolic)-poly(ethylene glycol) (PLGA-PEG) mucodiffusive nanoparticles (NPs) was designed. Specifically, these were decorated with site-specific conjugated human albumin, engineered for improved pH dependent binding to the neonatal Fc receptor (FcRn), which naturally mediates transport of albumin across the intestinal epithelium. The designed NPs of monodisperse 150 nm in size were 10% loaded with insulin and their surface was successfully functionalized with human albumin. Importantly, the engineered albumin-functionalized NPs bound human FcRn favorably in a pH dependent manner and showed enhanced transport across polarized cell layers. When orally administered to human FcRn expressing mice induced with diabetes, a reduction of glycemia was measured as a function of receptor targeting, with up to around 40% reduction after 1 h post-delivery. Thus, biodegradable PLGA-PEG NPs decorated with human albumin for improved FcRn-dependent transport offer a novel attractive strategy for delivery of encapsulated biopharmaceuticals across intestinal barriers. Keywords: Engineered albumin variants FcRn binding Glycemic decrease Intestinal permeability PLGA-PEG nanoparticles Type 1 diabetes mellitus”

Nuplon White-Paper technical documents out for dye/colorizing and electrical applications

Friday, July 31, 2020, 1:33 PM ET

Nuplon, a thermoset biodegradable polymer recently developed by Akina, Inc., is still under testing for a wide array of household and commodity uses. Two recent technical white-papers have come out reporting on the application of Nuplon towards dyed/colorized products (http://akinainc.com/pdf/Nuplon%20Technical%20Application%20Dye.pdf) as well as for use in forming electrical circuitry (http://akinainc.com/pdf/Nuplon%20Technical%20Application%20electrical.pdf).

PLGA-PEG-Folate and PLGA from PolySciTech used in Drug-delivery research

Friday, July 31, 2020, 12:02 PM ET

Medicinal molecules are only useful if they can reach the site of action. Often, this is simple for drugs such as acetaminophen (Tylenol) which are generic in nature, have relatively little side effects, and can be dosed orally. However for other drugs which do not dissolve well or are required to be delivered to a very specific location, advanced formulation strategies are necessary. Recently, researchers at University of Texas at El Paso used PLGA (AP081) and PLGA-PEG-Folate (AI168) from Polyscitech (www.polyscitech.com) to produce lutein-loaded nanoparticles for testing drug delivery to brain as a treatment for low-oxygen content disease states. This research holds promise to improve therapies against cancer and other disease states which require careful location of drugs. Read more: Bolla, Pradeep Kumar. "Formulation Strategies To Enhance Solubility And Permeability Of Small Molecules For Drug Delivery Applications." PhD diss., The University of Texas at El Paso, 2020. http://search.proquest.com/openview/444a9cea66942e5b372da6e7c3fd2394/1?pq-origsite=gscholar&cbl=18750&diss=y

“Perinatal asphyxia caused due to hypoxia complicates and causes hypoxic-ischemic encephalopathy (HIE). Therapeutic hypothermia widely used to treat HIE and is successful in 50%-60% patient population. It was reported that lutein supplementation showed neuroprotective properties in rat model of neonatal HIE. Lutein has poor bioavailability owing to poor aqueous solubility. In the second study, lutein was encapsulated into polymeric nanoparticles (PLGA and PLGA-PEG-FOLATE) and evaluated enhanced uptake in human neuroblastoma cells. Lutein loaded polymeric nanoparticles were prepared using O/W emulsion solvent-evaporation technique. Particle diameter and zeta potential (ZP) were measured using dynamic light scattering (DLS). Other characterizations included DSC, FTIR, SEM, and in vitro release studies. In vitro uptake studies were conducted in neuroblastoma cells using flow cytometry, confocal microscopy and high-performance liquid chromatography analysis. Lutein was successfully encapsulated into PLGA and PLGA-PEG-FOLATE nanoparticles with uniform size distribution of around 200 nm and high ZP. Entrapment efficiency of lutein was ~61% and ~73% for lutein PLGA and PLGAPEG-FOLATE nanoparticles, respectively. DSC and FTIR confirmed encapsulation of lutein into nanoparticles. Cumulative release of lutein was higher in PLGA nanoparticles with 100% release within 24 hours. In PLGA-PEG-FOLATE nanoparticles, cumulative release was ~80% at ix 48 hours. Cellular uptake studies in neuroblastoma cells confirmed a significant increase in lutein uptake with PLGA-PEG-FOLATE nanoparticles compared to PLGA nanoparticles and lutein alone. Findings from this study suggest that lutein loaded PLGA-PEG-FOLATE nanoparticles can be potentially used for treatment of HIE.”

New Product: Nuplon™: Environmentally-Friendly Biodegradable Plastic for Commodity Applications

Wednesday, July 22, 2020, 1:49 PM ET

The prevalence of non-degradable plastics has created an environmental hazard in oceans and forests across the planet. In addition to the medical research products, Akina, Inc. has developed a novel, commercially-viable, plastic which breaks down to non-toxic compounds over the course of 2-3 months with water exposure. This patent-pending technology allows for the creation of hard, heat-resistant crosslinked plastics which can be machined into a variety of shapes for a wide array of applications. Learn more at http://www.nuplon.com/

New Category: AD*** Modified Lipids

Wednesday, July 22, 2020, 1:48 PM ET

One of the oldest and most well-known classes of drug solublization products is modifying bio-inspired phospholipids with hydrophilic compounds (such as PEG) to create micelle-forming compounds with long circulation time. Recently, Akina, Inc. has added a new class of research products to the PolySciTech line to provide for modified lipid materials. You can see this new class here https://akinainc.com/polyscitech/products/polyvivo/index.php#LipidDerivatives

New Category: AX*** Polyoxazoline Derivatives

Wednesday, July 22, 2020, 1:47 PM ET

Although poly(ethylene glycol) is popular for use as a hydrophilic, water soluble polymer in biomedical applications it is not the only polymer which can fulfill this role. A growing body of evidence is showing that Polyoxazoline can provide for hydrophilic stabilization of block copolymers without some of the drawbacks characteristic of PEG. Recently, Akina, Inc. has added a new class of research products to the PolySciTech line to provide for polyoxazoline derivative materials. You can see this new class here https://akinainc.com/polyscitech/products/polyvivo/index.php#PolyoxazolineDerivatives

PLGA from PolySciTech used in research on bone tissue repair materials.

Wednesday, July 22, 2020, 1:46 PM ET

Bone tissue can not heal if the damage to an area of the bone is larger than a certain size (referenced as a critical defect size). In this case the bone may heal around the damage but can not bridge the gap to fill it in. In this case, often, a bone-scaffold material is surgically implanted to provide for improved healing. Recently, researchers at Southern Medical University (China) and The Pennsylvania State University developed novel biomaterials to test for their ability to provide for guided regeneration of bone. PLGA (AP154) from PolySciTech (www.polyscitech.com) was used as a comparison item to provide control data for biocompatibility and other parameters. This research holds promise to improve bone repair due to injury or disease. Read more: Guo, Jinshan, Xinggui Tian, Denghui Xie, Kevin Rahn, Ethan Gerhard, Michelle Laurel Kuzma, Dongfang Zhou et al. "Citrate‐Based Tannin‐Bridged Bone Composites for Lumbar Fusion." Advanced Functional Materials (2020): 2002438. https://onlinelibrary.wiley.com/doi/abs/10.1002/adfm.202002438

“Conventional bone composites consistently fail to mimic the chemical composition and integrated organic/inorganic structure of natural bone, lacking sufficient mechanics as well as inherent osteoconductivity and osteoinductivity. Through a facile surface coating process, the strong adhesive, tannic acid (TA), is adhered to the surface of the natural bone component, hydroxyapatite (HA), with and without the immobilization of in situ formed silver nanoparticles. Residual functional groups available on the immobilized TA substituents are subsequently covalently linked to the citrate‐based biodegradable polymer, poly(octamethylene citrate) (POC), effectively bridging the organic and inorganic phases. Due to the synergistic effects of the tannin and citrate components, the obtained citrate‐based tannin‐bridged bone composites (CTBCs) exhibit vastly improved compression strengths up to 323.0 ± 21.3 MPa compared to 229.9 ± 15.6 MPa for POC‐HA, and possess tunable degradation profiles, enhanced biomineralization performance, favorable biocompatibility, increased cell adhesion and proliferation, as well as considerable antimicrobial activity. In vivo study of porous CTBCs using a lumbar fusion model further confirms CTBCs' osteoconductivity and osteoinductivity, promoting bone regeneration. CTBCs possess great potential for bone regeneration applications while the immobilized TA additionally preserves surface bioconjugation sites to further tailor the bioactivity of CTBCs.”

Free PolySciTech Mask with Order

Tuesday, July 21, 2020, 4:54 PM ET

Every order from www.polyscitech.com comes with a free, cloth, non-medical face-mask while supplies last.

PLGA-PEG-Mal from PolySciTech used in development of angiogenesis controlling nanoparticles

Monday, July 20, 2020, 3:42 PM ET

Angiogenesis, the process by which blood vessels form and are grown, is a complicated biochemical process controlled by multiple signaling pathways. By providing a molecule which interacts with these pathways the growth of blood vessels can be controlled. This is an important pathway in terms of cancer treatment as cancers are often associated with inappropriate growth of blood vessels. Recently, researchers from Utrecht University, Royal Netherlands Academy of Arts and Sciences and University Medical Center Utrecht, University Medical Center Utrecht (Netherlands) utilized PLGA-PEG-Mal (AI020) from PolySciTech to develop RGD-targeted nanoparticles for endothelial targeting. This research holds promise to provide for better control of angiogenesis as a treatment option for cancer and other disease states. Read more: Martínez-Jothar, Lucía, Arjan D. Barendrecht, Anko M. de Graaff, Sabrina Oliveira, Cornelus F. van Nostrum, Raymond M. Schiffelers, Wim E. Hennink, and Marcel HAM Fens. "Endothelial Cell Targeting by cRGD-Functionalized Polymeric Nanoparticles under Static and Flow Conditions." Nanomaterials 10, no. 7 (2020): 1353. https://www.mdpi.com/2079-4991/10/7/1353

“Abstract: Since αvβ3 integrin is a key component of angiogenesis in health and disease, Arg-Gly-Asp (RGD) peptide-functionalized nanocarriers have been investigated as vehicles for targeted delivery of drugs to the αvβ3 integrin-overexpressing neovasculature of tumors. In this work, PEGylated nanoparticles (NPs) based on poly(lactic-co-glycolic acid) (PLGA) functionalized with cyclic-RGD (cRGD), were evaluated as nanocarriers for the targeting of angiogenic endothelium. For this purpose, NPs (~300 nm) functionalized with cRGD with different surface densities were prepared by maleimide-thiol chemistry and their interactions with human umbilical vein endothelial cells (HUVECs) were evaluated under different conditions using flow cytometry and microscopy. The cell association of cRGD-NPs under static conditions was time-, concentration- and cRGD density-dependent. The interactions between HUVECs and cRGD-NPs dispersed in cell culture medium under flow conditions were also time- and cRGD density-dependent. When washed red blood cells (RBCs) were added to the medium, a 3 to 8-fold increase in NPs association to HUVECs was observed. Moreover, experiments conducted under flow in the presence of RBC at physiologic hematocrit and shear rate, are a step forward in the prediction of in vivo cell–particle association. This approach has the potential to assist development and high-throughput screening of new endothelium-targeted nanocarriers. Keywords: nanoparticles; endothelial cells; RGD; targeting; physiological flow; PLGA”

These posts are syndicated from John Garner's blog at http://jgakinainc.blogspot.com/ where you can post a question or comment. (Load took 0.64447498321533 seconds)


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