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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PEG-PLGA from PolySciTech used in research on PEGylated long-circulating nanoparticles

Monday, August 20, 2018, 3:43 PM ET

One of the mechanisms for loss of nanoparticles from the blood-stream is removal by macrophages. This process is particularly pronounced in the liver, where particles are up-taken as part of hepatic clearance of ‘non-self’ components from the blood-stream. One means of preventing macrophage uptake is the addition of a pegylated shell to the outside of the nanoparticle as PEG reduces non-specific protein adsorption. Recently, researchers at Drexel University utilized mPEG-PLGA (PolyVivo AK037) from PolySciTech (www.polyscitech.com) to generate PEGylated nanoparticles and tested the particles under a variety of conditions to obtain a better understanding of how these particles can be modified to prevent clearance from the blood-stream. This research holds promise for the development of improved long-circulating nanoparticle drug-delivery systems. Read more: Zhou, Hao, Zhiyuan Fan, Peter Y. Li, Junjie Deng, Dimitrios C. Arhontoulis, Christopher Y. Li, Wilbur B. Bowne, and Hao Cheng. "Dense and Dynamic Polyethylene Glycol Shells Cloak Nanoparticles from Uptake by Liver Endothelial Cells for Long Blood Circulation." ACS nano (2018). https://pubs.acs.org/doi/abs/10.1021/acsnano.8b04947

“Research into long-circulating nanoparticles has in the past focused on reducing their clearance by macrophages. By engineering a hierarchical polyethylene glycol (PEG) structure on nanoparticle surfaces, we revealed an alternative mechanism to enhance nanoparticle blood circulation. The conjugation of a second PEG layer at a density close to, but lower than the mushroom-to-brush transition regime on conventional PEGylated nanoparticles dramatically prolongs their blood circulation via reduced nanoparticle uptake by non-Kupffer cells in the liver, especially liver sinusoidal endothelial cells (LSECs). Our study also disclosed that the dynamic outer PEG layer reduces protein binding affinity to nanoparticles, although not the total number of adsorbed proteins. These effects of the outer PEG layer diminishes in the higher density regime. Therefore, our results suggest that the dynamic topographical structure of nanoparticles is an important factor in governing their fate in vivo. Taken together, this study advances our understanding of nanoparticle blood circulation and provides a facile approach for generating long circulating nanoparticles.”

BPCR conference (August 29, 2018 9AM - 4PM: Kurz Purdue Technology Center, West Lafayette, IN) is a free, 1-day scientific-networking conference hosted by Akina, Inc. See more BPCRconference.com.

PLGA from PolySciTech used in development of localized anti-restenosis treatment for use in cardiovascular surgery

Monday, August 20, 2018, 3:41 PM ET

One of the complications which commonly results from mechanical-type heart-therapy, such as balloon angioplasty, stenosis, or other surgical techniques, is the occurrence of restenosis due to rapid regrowth of the tissue of the arterial walls in response to mechanical stress/damage. This natural tissue reaction to damage hinders the usefulness of these therapeutic techniques by reclosing the vessel. Recently, researchers at University of California and Harvard Medical School used multiple types of PLGA (Polyvivo AP021 and others) from PolySciTech (www.polyscitech.com) to design a system to release resolving D1 into the arterial walls, which prevents excessive inflammation and restenosis. This research holds promise to reduce the incidence of this potentially life-threatening complication. Read more: Wu, Bian, Evan C. Werlin, Mian Chen, Giorgio Mottola, Anuran Chatterjee, Kevin D. Lance, Daniel A. Bernards et al. "Perivascular delivery of resolvin D1 inhibits neointimal hyperplasia in a rabbit vein graft model." Journal of vascular surgery (2018). https://www.sciencedirect.com/science/article/pii/S0741521418313491

“Abstract: Objective: Inflammation is a key driver of excessive neointimal hyperplasia within vein grafts. Recent work demonstrates that specialized proresolving lipid mediators biosynthesized from omega-3 polyunsaturated fatty acids, such as resolvin D1 (RvD1), actively orchestrate the process of inflammation resolution. We investigated the effects of local perivascular delivery of RvD1 in a rabbit vein graft model. Methods: Ipsilateral jugular veins were implanted as carotid interposition grafts through an anastomotic cuff technique in New Zealand white rabbits (3-4 kg; N = 80). RvD1 (1 μg) was delivered to the vein bypass grafts in a perivascular fashion, using either 25% Pluronic F127 gel (Sigma-Aldrich, St. Louis, Mo) or a thin bilayered poly(lactic-co-glycolic acid) (PLGA) film. No treatment (bypass only) and vehicle-loaded Pluronic gels or PLGA films served as controls. Delivery of RvD1 to venous tissue was evaluated 3 days later by liquid chromatography-tandem mass spectrometry. Total leukocyte infiltration, macrophage infiltration, and cell proliferation were evaluated by immunohistochemistry. Elastin and trichrome staining was performed on grafts harvested at 28 days after bypass to evaluate neointimal hyperplasia and vein graft remodeling. Results: Perivascular treatments did not influence rates of graft thrombosis (23%), major wound complications (4%), or death (3%). Leukocyte (CD45) and macrophage (RAM11) infiltration was significantly reduced in the RvD1 treatment groups vs controls at 3 days (60%-72% reduction; P < .01). Cellular proliferation (Ki67 index) was also significantly lower in RvD1-treated vs control grafts at 3 days (40%-50% reduction; P < .01). Treatment of vein grafts with RvD1-loaded gels reduced neointimal thickness at 28 days by 61% vs bypass only (P < .001) and by 63% vs vehicle gel (P < .001). RvD1-loaded PLGA films reduced neointimal formation at 28 days by 50% vs bypass only (P < .001). RvD1 treatment was also associated with reduced collagen deposition in vein grafts at 28 days. Conclusions: Local perivascular delivery of RvD1 attenuates vein graft hyperplasia without associated toxicity in a rabbit carotid bypass model. This effect appears to be mediated by both reduced leukocyte recruitment and decreased cell proliferation within the graft. Perivascular PLGA films may also impart protection through biomechanical scaffolding in this venous arterialization model. Our studies provide further support for the potential therapeutic role of specialized proresolving lipid mediators such as D-series resolvins in modulating vascular injury and repair. Clinical Relevance: Autologous vein bypass grafts are the most durable means for revascularization in peripheral vascular disease; however, midterm and long-term outcomes are limited by vein graft hyperplasia with associated vein graft failure. Endogenous proresolving lipid mediators such as resolvin D1 have the potential to attenuate vein graft hyperplasia by accelerating repair. This study provides proof of concept for local delivery of resolvin D1 to reduce inflammation and to improve the healing response after vein bypass grafting. Keywords: Inflammation Resolution Resolvins Lipid mediator Neointimal hyperplasia Vein graft”

BPCR conference (August 29, 2018 9AM - 4PM: Kurz Purdue Technology Center, West Lafayette, IN) is a free, 1-day scientific-networking conference hosted by Akina, Inc. See more BPCRconference.com.

PLGA-NHS from PolySciTech used in development of hybrid nanoparticles for photo-immunotherapy as cancer treatment

Wednesday, August 15, 2018, 4:09 PM ET

The visible spectrum of light encompasses only a small sliver of available electromagnetic range. Light with wavelengths just slightly past the human visible range are referred to as near-infra-red light and such light is routinely used in house-hold items such as television remote controls and garage-door sensors. This light has the ability to pierce through human tissue and illuminate regions inside which gives it promise for use as a photo-activation method for cancer treatment. In photo-therapy, a medicine is applied which is not active until it encounters light. Afterwards, the region of the tumor is illuminated so that the therapy is activated only in that location. Recently, researchers from Yeungnam University, Daegu Haany University, and Hanyang University (Korea) used PLGA-NHS (PolyVivo AI097) from PolySciTech (www.polyscitech.com) to develop imatinib-loaded nanoparticles and conjugate the activated n-hydroxysuccinimide ester endcap of the PLGA to glucocorticoid-induced TNF receptor. These nanoparticles were tested and found to be activated by exposure to tissue-penetrating near-infrared light at 780 nm resulting in tumor necrosis. This research holds promise for treating cancers with minimal side-effects. Read more: Ou W, Jiang L, Thapa RK, Soe ZC, Poudel K, Chang JH, Ku SK, Choi HG, Yong CS, Kim JO. Combination of NIR therapy and regulatory T cell modulation using layer-by-layer hybrid nanoparticles for effective cancer photo-immunotherapy. Theranostics 2018; 8(17):4574-4590. doi:10.7150/thno.26758. Available from http://www.thno.org/v08p4574.htm

“The efficacy of combined near-infrared (NIR) and immune therapies for inhibiting tumor growth and recurrence has gained increasing research attention. Regulatory T cells in the tumor microenvironment constitute a major obstacle in achieving robust CD8+ T cell antitumor immunotherapy. In the present study, we designed a photoimmunotherapy-based strategy involving a combination of photothermal and photodynamic therapies, followed by Treg cell suppression, for eliciting an immune response with IR-780- and imatinib-loaded layer-by-layer hybrid nanoparticles. Methods: The layer-by-layer hybrid nanoparticles were prepared through electrostatic interactions. Their photothermal effect, photodynamic effect as well as their effect on inhibiting Treg cells' suppressive function were investigated in vitro and in vivo. Their antitumor effect was evaluated using B16/BL6 and MC-38 tumor-bearing mice. Results: The layer-by-layer hybrid nanoparticles, which were pH-sensitive, enabled the release of IR-780 dye for NIR-induced photothermal and photodynamic effects, and the release of imatinib-loaded glucocorticoid-induced TNF receptor family-related protein/poly(lactic-co-glycolic acid) (GITR-PLGA) nanoparticles to initiate antitumor immunotherapy. The photothermal and photodynamic effects caused by IR-780 under NIR exposure resulted in direct tumor apoptosis/necrosis and the production of tumor-associated antigen, promoted dendritic cell maturation, and enhanced the presentation of tumor-associated antigen to T cells, while the imatinib-loaded GITR-PLGA cores reduced the suppressive function of Treg cells, and consequently activated effective CD8+ T cells towards tumors. Conclusion: With the significant photothermal, photodynamic and immunotherapies, the system successfully eradicated tumor growth, diminished tumor recurrence, and improved survival in vivo. The proposed nanoparticles provide a novel and versatile approach to boost antitumor photoimmunotherapy. Keywords: imatinib, immunotherapy, IR-780, layer by layer, photodynamic therapy, photothermal therapy, Treg cell”

BPCR conference (August 29, 2018 9AM - 4PM: Kurz Purdue Technology Center, West Lafayette, IN) is a free, 1-day scientific-networking conference hosted by Akina, Inc. See more BPCRconference.com.

PLGA-PEG-COOH from PolySciTech used in development of antigen-labelled nanoparticles for colorectal cancer therapy

Wednesday, August 15, 2018, 4:08 PM ET

Colorectal cancer is one of the most commonly diagnosed cancers worldwide. The severe side effects of most chemotherapeutics used for treating this cancer limit their dosage. Use of a delivery system to improve uptake of the medicinal molecules to the cancer site can improve efficacy and reduce side-effects. Recently, researchers at Universidade do Porto, Universitario de Ciencias da Saude (Portugal), and Queen’s University Belfast (UK) used PLGA-PEG-COOH (PolyVivo AI076) from PolySciTech (www.polyscitech.com) to generate paclitaxel-loaded nanoparticles with –COOH groups along the exterior. They used carbodiimide/NHS conjugation methodologies to attach a carcinoembryonic antibody to the exterior of the particle for ligand-attachment to cancer cells. This research holds promise for improved therapies for colorectal cancer. Read more: Pereira, Ines, Flavia Sousa, Patrick Kennedy, Bruno Sarmento “Carcinoembryonic antigen-targeted nanoparticles potentiate the delivery of anticancer drugs to colorectal cancer cells” International Journal of Pharmaceutics Volume 549, Issues 1–2, 5 October 2018, Pages 397-403 https://www.sciencedirect.com/science/article/pii/S0378517318305787

“Abstract: Bioengineered functionalized nanoparticles have extensively been proposed in recent years to efficiently deliver anti-cancer drugs to the tumour site, by targeting the cancer cells and improving the therapeutic efficiency of active molecules. In this work, polymeric poly (lactic-co- glycolic)-polyethylene glycol (PLGA-PEG) nanoparticles were produced by nanoprecipitation and loaded with paclitaxel, following surface-functionalized with a monoclonal antibody targeting the carcinoembryonic antigen (CEA) of intestinal epithelial cells. Physicochemical properties, cytotoxicity and targeting ability of the nanoparticles against two intestine epithelial carcinoma cell lines, CEA-expressing Caco-2 clone and non-CEA-expressing SW480, were assessed. Results showed successful production of nanoparticles around 200 nm, and close to charge neutrality, encapsulating up to 99% of paclitaxel. Functionalized nanoparticles were further constructed, demonstrating to be non-cytotoxic against intestinal cells. The targeting ability of functionalized nanoparticles to Caco-2 CEA expressing cells was confirmed by flow cytometry, in opposite to SW480 cells. Overall, the surface-modified PLGA-PEG nanoparticles with the CEA-targeting antibody were successfully developed as nanocarriers for paclitaxel and interacted with CEA expressing cells. This specific interaction provide these particles ability to be used as targeted systems for colorectal cancer therapeutics. Keywords: Drug delivery Carcinoembryonic antigen Targeted nanoparticles Colorectal cancer”

BPCR conference (August 29, 2018 9AM - 4PM: Kurz Purdue Technology Center, West Lafayette, IN) is a free, 1-day scientific-networking conference hosted by Akina, Inc. See more BPCRconference.com.

BPCR Conference

Monday, August 6, 2018, 3:13 PM ET

BPCR conference (August 29, 2018 9AM - 4PM: Kurz Purdue Technology Center, West Lafayette, IN) is a free, 1-day scientific-networking conference hosted by Akina, Inc. See more BPCRconference.com.

PLGA from PolySciTech used in development of bio-inspired nanoparticles for improved circulation times as part of cancer treatment

Wednesday, August 1, 2018, 11:54 AM ET

The human immune system is quite adept at attacking anything which is perceived as ‘non-self,’ including medicinal delivery systems such as nanoparticles. Once the particles are identified as ‘non-self’, white-blood cells and other macrophages clear them rapidly out of the blood stream limiting their capacity to deliver medicine to their intended destination. Recently, researchers at Beihua University (China) used PLGA (PolyVivo Cat# AP041) from PolySciTech (www.polyscitech.com) to create docetaxel-loaded nanoparticles. These particles were subsequently coated with red-blood-cell membrane components to ‘disguise’ the particles, making them appear ‘self’ to macrophages. This strategy improves the nanoparticles longevity in the blood-stream and functional uptake to their intended target. This research holds promise for improved chemotherapeutic treatments in the future. Read more: Xu, Lei, Shuo Wu, and Xiaoqiu Zhou. "Bioinspired nanocarriers for an effective chemotherapy of hepatocellular carcinoma." Journal of Biomaterials Applications (2018): 0885328218772721. http://journals.sagepub.com/doi/abs/10.1177/0885328218772721

“Abstract: Drug-loaded nanoparticles have been widely researched in the antitumor. However, some of them are unsatisfactory in the long blood circulation and controlled drug release. Red blood cell (RBC) membrane vesicles (RV)-coated nanoparticles have gained more and more attention in drug delivery for their many unique advantages, such as excellent stability, long blood circulation, and reduced the macrophage cells uptake. Herein, by utilizing the advantages of RV, we fabricated RV-coated poly(lactide-co-glycolide) (PLGA)–docetaxel (RV/PLGA/DTX) nanoparticles to enhance the antitumor efficiency in vivo. The RV/PLGA/DTX showed spherical morphology with particle size of about 100 nm and zeta potential at −12.63 mV, which could maintain stability for a long time. The RV/PLGA/DTX significantly enhanced cellular uptake of DTX compared to PLGA/DTX in HepG2 cells. Moreover, RV/PLGA/DTX showed the strongest antitumor effect in vitro. Prolonged blood circulation and enhanced DTX accumulation at the tumor site through enhanced permeability and retention (EPR) effect were achieved by RV/PLGA/DTX, which eventually obtained satisfactory antitumor effect and depressed system toxicity on mice bearing HepG2 xenografts mouse models when compared with free DTX. The hematoxylin and eosin (H&E) and immunofluorescence assays further proved the advantages of RV/PLGA/DTX in vivo antitumor. These RV-coated nanoparticles provide a mimetic therapy, completely inhibited the growth of the HepG2 cells, and with simple compositions, suggesting it to be an ideal strategy for improving the antitumor effect of drug-loaded nanoparticles. Keywords: Controlled drug delivery, docetaxel, malignancy therapeutics, PLGA nanoparticles, RBC-mimetic”

BPCR conference (August 29, 2018 9AM - 4PM: Kurz Purdue Technology Center, West Lafayette, IN) is a free, 1-day scientific-networking conference hosted by Akina, Inc. See more BPCRconference.com.

PLGA from PolySciTech used in development of brain-cancer targeting liposome therapy

Wednesday, August 1, 2018, 11:53 AM ET

A common problem which afflicts all brain-treatment methodologies is the presence of the blood-brain-barrier, a system which prevents most medicines in the bloodstream from crossing over into the brain cavity. Overcoming this barrier is not a trivial task and necessary for treating ailments ranging from glioblastoma to Alzheimer’s disease. Recently, researchers from North Dakota State University utilized PLGA (PolyVivo cat# AP022) from PolySciTech (www.polyscitech.com) combined with chitosan to develop an in-vitro brain tumor model to test uptake by cancer cells of 5-FU loaded liposomes. This research holds promise to improve therapeutic options for brain cancer. Read more: Lakkadwala, Sushant, and Jagdish Singh. "Dual Functionalized 5-Fluorouracil Liposomes as Highly Efficient Nanomedicine for Glioblastoma Treatment as Assessed in an In Vitro Brain Tumor Model." Journal of Pharmaceutical Sciences (2018). https://www.sciencedirect.com/science/article/pii/S0022354918304556

“Abstract: Drug delivery to the brain has been a major challenge due to the presence of the blood brain barrier (BBB), which limits the uptake of most chemotherapeutics into brain. We developed a dual-functionalized liposomal delivery system, conjugating cell penetrating peptide penetratin to transferrin-liposomes (Tf-Pen-conjugated liposomes) to enhance the transport of an anticancer chemotherapeutic drug, 5-fluorouracil (5-FU), across the BBB into the tumor cells. The in vitro cellular uptake study showed that the dual-functionalized liposomes are capable of higher cellular uptake in glioblastoma (U87) and brain endothelial (bEnd.3) cells monolayer. In addition, dual-functionalized liposomes demonstrated significantly higher apoptosis in U87 cells. The liposomal nanoparticles showed excellent blood compatibility and in vitro cell viability, as studied by hemolysis and MTT assay, respectively. The 5-FU loaded dual-functionalized liposomes demonstrated higher transport across the brain endothelial barrier and delivered 5-FU to tumor cells inside PLGA-chitosan scaffold (an in vitro brain tumor model), resulting in significant tumor regression. Keywords: blood brain barrier liposomes nanomedicine biocompatibility cancer chemotherapy targeted drug delivery”

BPCR conference (August 29, 2018 9AM - 4PM: Kurz Purdue Technology Center, West Lafayette, IN) is a free, 1-day scientific-networking conference hosted by Akina, Inc. See more BPCRconference.com.

Fluorescent PLGA-rhodamine from PolySciTech used to investigate albumin-coating for nanoparticle transport

Thursday, July 26, 2018, 9:19 AM ET

There is nothing more annoying than carefully crafting a nanoparticle system only to watch the drug-loaded therapeutic particles be gobbled up by macrophages (white blood cells) as soon as they are introduced into the blood-stream. There are many ways to protect the nanoparticles from the immune system, one of which is to provide an albumin coating that the immune system will generally recognize as ‘self’ and not attack. However, to be recognized, the albumin protein must be in the right shape and conformation and this property can be affected by ‘how’ it is coated onto the particle. Recently, researchers at Purdue University and Seoul National University utilized PLGA (PolyVivo Cat# AP031) and PLGA-rhodamine B endcap (PolyVivo Cat# AV011) from PolySciTech (www.polyscitech.com) to create nanoparticles which were coated with albumin by various techniques and they tracked the motion and fate of these particles using fluorescent techniques. This research holds promise for providing for improved nanotherapy in the future. Read more: Hyun, Hyesun, Joonyoung Park, Kiela Willis, Ji Eun Park, L. Tiffany Lyle, Wooin Lee, and Yoon Yeo. "Surface modification of polymer nanoparticles with native albumin for enhancing drug delivery to solid tumors." Biomaterials (2018). https://www.sciencedirect.com/science/article/pii/S0142961218305088

“Abstract: Albumin is a promising surface modifier of nanoparticulate drug delivery systems. Serving as a dysopsonin, albumin can protect circulating nanoparticles (NPs) from the recognition and clearance by the mononuclear phagocytic system (MPS). Albumin may also help transport the NPs to solid tumors based on the increased consumption by cancer cells and interactions with the tumor microenvironment. Several studies have explored the benefits of surface-bound albumin to enhance NP delivery to tumors. However, it remains unknown how the surface modification process affects the conformation of albumin and the performance of the albumin-modified NPs. We use three different surface modification methods including two prevalent approaches (physisorption and interfacial embedding) and a new method based on dopamine polymerization to modify the surface of poly(lactic-co-glycolic acid) NPs with albumin and compare the extent of albumin binding, conformation of the surface-bound albumin, and biological performances of the albumin-coated NPs. We find that the dopamine polymerization method preserves the albumin structure, forming a surface layer that facilitates NP transport and drug delivery into tumors via the interaction with albumin-binding proteins. In contrast, the interfacial embedding method creates NPs with denatured albumin that offers no particular benefit to the interaction with cancer cells but rather promotes the MPS uptake via direct and indirect interactions with scavenger receptor A. This study demonstrates that the surface-bound albumin can bring distinct effects according to the way they interact with NP surface and thus needs to be controlled in order to achieve favorable therapeutic outcomes.”

BPCR conference (August 29, 2018 9AM - 4PM: Kurz Purdue Technology Center, West Lafayette, IN) is a free, 1-day scientific-networking conference hosted by Akina, Inc. See more BPCRconference.com.

PLGA-Poly(lysine) from PolySciTech used in development of stem-cell based nerve-tissue repair model

Thursday, July 26, 2018, 9:17 AM ET

The lack of natural nerve-tissue repair is one of the leading factors in a variety of diseases and traumatic injuries including spinal cord injury, brain-damage (due to injury or lack of blood flow), and peripheral nerve damage. Nerve tissue does not naturally heal well making the damage from these events permanent over a life-time. Stem-cells are generic precursor cells which can become any type of cell (i.e. muscle, fat, skin, nerve, bone, etc.). These hold promise to provide for repair of a wide variety of tissues, when cultured and handled under the right conditions that encourage these cells to become (differentiate) into the specific cell-type for that tissue. Recently, researchers at Harvard used PLGA-Polylysine (AI028) from PolySciTech (www.polyscitech.com) as part of development of research tool for investigating neural cell development from stem-cells. This research holds promise to enable further development of neural-tissue engineering. Read more: Thakor, Devang K., Lei Wang, Darcy Benedict, Serdar Kabatas, Ross D. Zafonte, and Yang D. Teng. "Establishing an Organotypic System for Investigating Multimodal Neural Repair Effects of Human Mesenchymal Stromal Stem Cells." Current protocols in stem cell biology (2018): e58. https://currentprotocols.onlinelibrary.wiley.com/doi/abs/10.1002/cpsc.58

“Abstract: Human mesenchymal stromal stem cells (hMSCs) hold regenerative medicine potential due to their availability, in vitro expansion readiness, and autologous feasibility. For neural repair, hMSCs show translational value in research on stroke, spinal cord injury (SCI), and traumatic brain injury. It is pivotal to establish multimodal in vitro systems to investigate molecular mechanisms underlying neural actions of hMSCs. Here, we describe a platform protocol on how to set up organotypic co‐cultures of hMSCs (alone or polymer‐scaffolded) with explanted adult rat dorsal root ganglia (DRGs) to determine neural injury and recovery events for designing implants to counteract neurotrauma sequelae. We emphasize in vitro hMSC propagation, polymer scaffolding, hMSC stemness maintenance, hMSC‐DRG interaction profiling, and analytical formulas of neuroinflammation, trophic factor expression, DRG neurite outgrowth and tropic tracking, and in vivo verification of tailored implants in rodent models of SCI.”

BPCR conference (August 29, 2018 9AM - 4PM: Kurz Purdue Technology Center, West Lafayette, IN) is a free, 1-day scientific-networking conference hosted by Akina, Inc. See more BPCRconference.com.

Akina CRS 2018 Posters now available online

Thursday, July 26, 2018, 9:15 AM ET

The full posters presented at 2018 CRS by Akina, Inc. These include CRS Poster # 95: J. Hadar, J. Garner, S. Skidmore, K. Park, H. Park, Y. K. Jhon, Y. Wang “Correlation Analysis of Refractive Index (dn/dc) for PLGAs with Different Ratios of Lactide to Glycolide” Presenter: Justin Hadar.; CRS Poster # 409: J. Hadar, J. Garner, S. Skidmore, K. Park, H. Park, D. Kozak, Y. Wang “Solvent-dependent PLGA solubility for separation of PLGAs with different lactide:glycolide ratios” Presenter: John Garner.) are now available in high-resolution pdf online on Akina’s publications page (http://polyscitech.com/currentResearch/publications.php)

BPCR conference (August 29, 2018 9AM - 4PM: Kurz Purdue Technology Center, West Lafayette, IN) is a free, 1-day scientific-networking conference hosted by Akina, Inc. See more BPCRconference.com.

Akina Presenting Scientific Posters at Controlled Release Society (2018) Meeting

Friday, July 20, 2018, 2:26 PM ET

Employees of Akina, Inc (www.akinainc.com) will be presenting scientific posters at the 2018 Controlled Release Society (CRS) annual meeting July 22-24th, 2018 New York, NY (https://2018.controlledreleasesociety.org/, #CRSNYC ). These posters are based on research projects supported by the Food and Drug Administration. This research primarily involves development of analytical methods for testing poly(lactide-co-glycolide) (PLGA) used in parental long-acting formulations. This research can help in developing methods to establish Q1/Q2 ‘sameness’ for depot-injectable type products. Make sure you take a moment to stop by these posters:

CRS Poster # 95: J. Hadar, J. Garner, S. Skidmore, K. Park, H. Park, Y. K. Jhon, Y. Wang “Correlation Analysis of Refractive Index (dn/dc) for PLGAs with Different Ratios of Lactide to Glycolide” Presenter: Justin Hadar.

CRS Poster # 409: J. Hadar, J. Garner, S. Skidmore, K. Park, H. Park, D. Kozak, Y. Wang “Solvent-dependent PLGA solubility for separation of PLGAs with different lactide:glycolide ratios” Presenter: John Garner.

PLGA/PLA standards now available from Akina, Inc.

Wednesday, July 18, 2018, 1:18 PM ET

Newly available PLGA standards with state-of-the-art characterization now available from PolySciTech. These standards include PLGA’s and PLA’s analyzed by several techniques including GPC-quadruple detection to have well characterized molecular weights and known solvated radii. See these standards here (https://akinainc.com/polyscitech/products/polyvivo/plga_pla_standards.php)

BPCR conference (August 29, 2018 9AM - 4PM: Kurz Purdue Technology Center, West Lafayette, IN) is a free, 1-day scientific-networking conference hosted by Akina, Inc. See more BPCRconference.com. Akina, Inc. will be closed this day and all orders placed will be filled the following day.

Protein Phosphorylation Detection Kit

Wednesday, July 18, 2018, 10:08 AM ET

Proteins Phosphorylated?
We know how you feel. Get your Tymora-Brand Protein Phosphorylation Detection Kit from Akina here (https://akinainc.com/polyscitech/products/tymora/index.php)

PEG-PLGA from PolySciTech used in development of iron-chelating micelle system to treat bacterial infections

Thursday, July 12, 2018, 2:55 PM ET

Iron is an essential nutrient for bacteria and plays a significant role in the growth and development of bacterial biofilm. One means of treating bacterial infections and diseases is to chelate out iron, thus making it unavailable for bacterial use. Recently, researchers at University of Georgia and University of Wisconsin–Madison utilized mPEG-PLGA (PolyVivo AK010) and PLGA-PEG-NH2 (PolyVivo AI058) from PolySciTech (www.polyscitech.com) as part of forming an iron-chelating micelle for treatment of bacterial infections. This research holds promise to provide for improved therapies against cystic fibrosis and other bacterial diseases. Read more: Qiao, Jing, Max Purro, Zhi Liu, and May P. Xiong. "Terpyridine-Micelles for Inhibiting Bacterial Biofilm Development." ACS infectious diseases (2018). https://pubs.acs.org/doi/abs/10.1021/acsinfecdis.8b00091

“Iron plays a critical role in bacterial infections and is especially critical for supporting biofilm formation. Until recently, Fe(III) was assumed to be the most relevant form of iron to chelate in therapeutic antimicrobial strategies due to its natural abundance under normal oxygen and physiologic conditions. Recent clinical data obtained from cystic fibrosis (CF) patients found that there is actually quite an abundance of Fe(II) present in sputum and that there exists a significant relationship between sputum Fe(II) concentration and severity of the disease. A biocompatible mixed micelle formed from the self-assembly of poly (lactic-co-glycolic acid)-block-methoxy poly(ethylene glycol) (PLGA-b-mPEG) and poly(lactic-co-glycolic acid)-block-poly(terpyridine)5 [PLGA-b-p(Tpy)5] polymers was prepared to chelate Fe(II) (Tpy‒micelle). Tpy-micelles showed high selectivity for Fe(II) over Fe(III), decreased biofilm mass more effectively under anaerobic conditions at >4 µM Tpy-micelles, reduced bacteria growth in biofilms by >99.9% at 128 µM Tpy-micelles, effectively penetrated throughout a 1-day old biofilm and inhibited biofilm development in a concentration-dependent manner. This study reveals that Fe(II) chelating Tpy-micelles are a promising addition to Fe(III) chelating strategies to inhibit biofilm formation in CF lung infections.”


New whitepaper on acrylate-modified HMMC (AI147) use for forming UV-cured hydrogels available. Hydrogels are a class of polymers with exciting potential to provide for tissue-engineering or cell-growth capabilities. Recently, a whitepaper “AI147 Photocrosslinkg application” has been released detailing the use of PolyVivo AI147 to create UV-curable hydrogels. See more here: (http://akinainc.com/pdf/AI147%20HMMC-Acrylate%20crosslinking%20and%20micromolding.pdf).


BPCR conference (August 29, 2018 9AM - 4PM: Kurz Purdue Technology Center, West Lafayette, IN) is a free, 1-day scientific-networking conference hosted by Akina, Inc. See more BPCRconference.com

Fluorescently-labeled and reactive-endcap polymers from PolySciTech used in development of photo-activated immunotherapy for treatment of cancer

Monday, July 9, 2018, 4:29 PM ET

Due to the fact that tumors are comprised of human patient cells, it is very difficult to create therapies which are selective in their damage against tumors. Most conventional treatments (chemotherapy, radiation, and surgical techniques) damage healthy tissue to some degree or another which limits the applicability of the treatment and causes a variety of side-effects for the patient. Recently, researchers at University of Maryland and Harvard University used Polyvivo reactive-endcap PLGA-PEG-COOH (Cat# AI034) and PLGA-PEG-azide (Cat# AI085) as well as fluorescent-endcap mPEG-PLGA-FKR560 (Cat# AV021) from PolySciTech (www.polyscitech.com) to create a photo-immunoconjugated nanoparticle. The unique feature of this particle is that it did not affect tissue until ‘triggered’ to do so by a light source allowing it to be targeted for affecting the cancer with great specificity. The researchers applied a unique technique of using a fluorescent end-cap PEG-PLGA, typically only used for tracking purposes, to serve as the trigger for these nanoparticles. This research holds promise for improved cancer therapies in the future. Read more: Huang, Huang‐Chiao, Michael Pigula, Yanyan Fang, and Tayyaba Hasan. "Immobilization of Photo‐Immunoconjugates on Nanoparticles Leads to Enhanced Light‐Activated Biological Effects." Small (2018): 1800236. https://onlinelibrary.wiley.com/doi/abs/10.1002/smll.201800236

“Abstract: The past three decades have witnessed notable advances in establishing photosensitizer–antibody photo‐immunoconjugates for photo‐immunotherapy and imaging of tumors. Photo‐immunotherapy minimizes damage to surrounding healthy tissue when using a cancer‐selective photo‐immunoconjugate, but requires a threshold intracellular photosensitizer concentration to be effective. Delivery of immunoconjugates to the target cells is often hindered by I) the low photosensitizer‐to‐antibody ratio of photo‐immunoconjugates and II) the limited amount of target molecule presented on the cell surface. Here, a nanoengineering approach is introduced to overcome these obstacles and improve the effectiveness of photo‐immunotherapy and imaging. Click chemistry coupling of benzoporphyrin derivative (BPD)–Cetuximab photo‐immunoconjugates onto FKR560 dye‐containing poly(lactic‐co‐glycolic acid) nanoparticles markedly enhances intracellular photo‐immunoconjugate accumulation and potentiates light‐activated photo‐immunotoxicity in ovarian cancer and glioblastoma. It is further demonstrated that co‐delivery and light activation of BPD and FKR560 allow longitudinal fluorescence tracking of photoimmunoconjugate and nanoparticle in cells. Using xenograft mouse models of epithelial ovarian cancer, intravenous injection of photo‐immunoconjugated nanoparticles doubles intratumoral accumulation of photo‐immunoconjugates, resulting in an enhanced photoimmunotherapy‐mediated tumor volume reduction, compared to “standard” immunoconjugates. This generalizable “carrier effect” phenomenon is attributed to the successful incorporation of photo‐immunoconjugates onto a nanoplatform, which modulates immunoconjugate delivery and improves treatment outcomes.”

BPCR conference (August 29, 2018 9AM - 4PM: Kurz Purdue Technology Center, West Lafayette, IN) is a free, 1-day scientific-networking conference hosted by Akina, Inc. See more BPCRconference.com

Flourescent-endcap PLGA from PolySciTech used to investigate whole-body imaging biodistribution methodologies

Thursday, June 28, 2018, 4:09 PM ET

Use of fluorescently-tagged PLGA allows for generated nanoparticles to be tracked using imaging systems. However, circumstances such as self-quenching can alter the results unless the research is performed in a careful and controlled manner. These situations can lead to erroneous results and alter the apparent uptake of nanoparticles into tumor sites relative to those up-taken by clearance through the liver, spleen, or kidneys. Recently, researchers at Purdue University use PLGA-Rhodamine (PolyVivo AV011), PLGA (AP020), and near-IR dye (FPI749) from PolySciTech (www.polyscitech.com) to evaluate the bio-distribution assays used to determine nanoparticle fate. This research holds promise to improve assessments of bio-distribution of nanoparticles in the future thus aiding in development of cancer therapies. Read more: Meng, Fanfei, Jianping Wang, Qineng Ping, and Yoon Yeo. "Quantitative Assessment of Nanoparticle Biodistribution by Fluorescence Imaging, Revisited." ACS nano (2018). https://pubs.acs.org/doi/abs/10.1021/acsnano.8b02881

“Abstract: Fluorescence-based whole body imaging is widely used in the evaluation of nanoparticles (NPs) in small animals, often combined with quantitative analysis to indicate their spatiotemporal distribution following systemic administration. An underlying assumption is that the fluorescence label represents NPs and the intensity increases with the amount of NPs and/or the labeling dyes accumulated in the region of interest. We prepare DiR-loaded poly(lactic-co glycolic acid) (PLGA) NPs with different surface layers (polyethylene glycol with and without folate terminus) and compare the distribution of fluorescence signals in a mouse model of folate receptor expressing tumor by near infrared fluorescence whole body imaging. Unexpectedly, we observe that fluorescence distribution patterns differ far more dramatically with DiR loading than with the surface ligand, reaching opposite conclusions with the same type of NPs (tumor-specific delivery vs. predominant liver accumulation). Analysis of DiR-loaded PLGA NPs reveal that fluorescence quenching, dequenching and signal saturation, which occur with the increasing dye content and local NP concentration, are responsible for the conflicting interpretations. This study highlights the critical need for validating fluorescence labeling of NPs in the quantitative analysis of whole body imaging. In light of our observation, we make suggestions for future whole body fluorescence imaging in the in vivo evaluation of NP behaviors. Keywords: Whole body imaging; fluorescence quenching; fluorescence saturation; nanoparticles; biodistribution”

BPCR conference (August 29, 2018 9AM - 4PM: Kurz Purdue Technology Center, West Lafayette, IN) is a free, 1-day scientific-networking conference hosted by Akina, Inc. See more BPCRconference.com

PLGA from PolySciTech used in development of salinomycin-loaded nanofiber mesh for treatment of brain-cancer

Tuesday, June 26, 2018, 2:23 PM ET

Glioblastoma is a very common and aggressive form of brain-cancer which has a very poor survival rate. Treatment is difficult as uptake of medicine across the blood-brain-barrier (BBB) is very poor so most medicines do not reach the affected area. One means of circumventing this is to implant a material directly into the brain cavity which releases a therapeutic agent. The choice of therapeutic agent is not trivial, however, as localized delivery to the brain requires that it have minimal toxicity towards normal cells. Salinomycin (a conventional antibiotic) has been found to also have excellent efficacy against cancer cells which provides an opportunity for selective cancer reduction by a biocompatible agent. Recently, researchers at the University of Manitoba used PLGA (PolyVivo AP045) from PolySciTech (www.polyscitech.com) to create an electrospun-mesh that delivered salinomycin in a time-released manner. This research holds promise for improved therapies against often lethal brain-cancers. Read more: Norouzi, Mohammad, Zahra Abdali, Song Liu, and Donald W. Miller. "Salinomycin-loaded Nanofibers for Glioblastoma Therapy." Scientific Reports 8, no. 1 (2018): 9377. https://www.nature.com/articles/s41598-018-27733-2

“Abstract: Salinomycin is an antibiotic that has recently been introduced as a novel and effective anti-cancer drug. In this study, PLGA nanofibers (NFs) containing salinomycin (Sali) were fabricated by electrospinning for the first time. The biodegradable PLGA NFs had stability for approximately 30 days and exhibited a sustained release of the drug for at least a 2-week period. Cytotoxicity of the NFs + Sali was evaluated on human glioblastoma U-251 cells and more than 50% of the treated cells showed apoptosis in 48 h. Moreover, NFs + Sali was effective to induce intracellular reactive oxygen species (ROS) leading to cell apoptosis. Gene expression studies also revealed the capability of the NFs + Sali to upregulate tumor suppressor Rbl1 and Rbl2 as well as Caspase 3 while decreasing Wnt signaling pathway. In general, the results indicated anti-tumor activity of the Sali-loaded NFs suggesting their potential applications as implantable drug delivery systems in the brain upon surgical resection of the tumor.”

BPCR conference (August 29, 2018 9AM - 4PM: Kurz Purdue Technology Center, West Lafayette, IN) is a free, 1-day scientific-networking conference hosted by Akina, Inc. See more BPCRconference.com

PLGA-PEG-PLGA from PolySciTech used in development of berberine nanoparticle for heart-disease therapy

Friday, June 22, 2018, 7:15 PM ET

Berberine is a historical herbal remedy garnering new attention over its capability to reduce cholesterol and provide for improved heart health. Due to its low bioavailability, its uptake and efficacy however can be improved by applying nanotechnology. Recently, researchers at University of Massachusetts Lowell used PLGA-PEG-PLGA (PolyVivo AK072) from PolySciTech (www.polyscitech.com) to generate nanoparticles loaded with berberine for improved oral uptake. This research holds promise to provide for improved therapies for high cholesterol and heart disease. Read more: Ochin, Chinedu C., and Mahdi Garelnabi. "Berberine Encapsulated PLGA-PEG Nanoparticles Modulate PCSK-9 in HepG2 Cells." Cardiovascular & Haematological Disorders-Drug Targets (Formerly Current Drug Targets-Cardiovascular & Hematological Disorders) 18, no. 1 (2018): 61-70. https://www.ingentaconnect.com/contentone/ben/chddt/2018/00000018/00000001/art00010

“Background: The developments of new parenteral approaches to target PCSK-9 for the treatment of LDL-Cholesterol has yielded impressive results; and have shown significant decreases in the risk of mortality associated with hypercholesterolemia. However improved and convenient alternate approaches that exploit the beneficial drug target properties of PCSK-9 also need to be explored and developed. One such approach is the oral administration of Berberine using nanotechnology. Methods: Nanoprecipitation encapsulation and physiochemical characterization of Berberine Chloride in PLGA-PEG-PLGA block copolymer has been developed and characterized in Hep-G2 cells using Berberine Chloride encapsulated nanoparticle (Bc-NP). Evaluation of PCSK-9, SREBP- 1, LDL-r, HNF-1alpha mRNAs and PCSK-9 protein expression was performed using quantitative real-time PCR (qPCR) and median fluorescence intensity (MFI) of flow cytometric studies respectively. Pearson's correlation analysis of PCSK-9 mRNA and protein levels in Berberine chloride delivery was performed. Results: The PCSK-9 mRNA and protein expression shows a relationship to the release of Berberine from the encapsulating PLGA-PEG-PLGA polymer in a time dependent manner. Conclusion: PCSK-9 modulation by oral administration of Berberine using nanotechnology approach can improve its pharmacokinetic profile. Further studies are needed to maximize its delivery efficiency. Keywords: PCSK9; atherosclerosis; drug delivery; lipids; lipoproteins; nanotechnology”

BPCR conference (August 29, 2018 9AM - 4PM: Kurz Purdue Technology Center, West Lafayette, IN) is a free, 1-day scientific-networking conference hosted by Akina, Inc. See more BPCRconference.com

PLGA from PolySciTech used in development of ceramic nanocomposites for tissue engineering applications

Tuesday, June 19, 2018, 8:31 PM ET

Advanced ceramics and bioactive polymers represent two classes of rapidly developing materials which hold great promise for a wide variety of applications. Tissue engineering refers to the regrowth of missing or damaged tissue and is a medical field which can be used for a wide variety of trauma cases or disease states. Typically, this requires some form of a scaffold or structure for the newly forming cells to grow on. Recently, researchers from University of California Riverside used PLGA (PolyVivo AP036) from PolySciTech (www.polyscitech.com) to develop a composite with both optical clarity as well as capacity to provide for cell growth. This composite has great promise for a wide variety of tissue engineering applications. Read more: Wetteland, Cheyann Lee, and Huinan Liu. "Optical and Biological Properties of Polymerbased Nanocomposites with Improved Dispersion of Ceramic Nanoparticles." Journal of Biomedical Materials Research Part A (2018). https://onlinelibrary.wiley.com/doi/abs/10.1002/jbm.a.36466

“Abstract: This article reports a new process for creating polymerbased nanocomposites with enhanced dispersion of ceramic nanoparticles without using any surfactants, and the resulted changes in their optical and biological properties. Specifically, dispersion of two different ceramic nanoparticles, i.e, hydroxyapatite (nHA) and magnesium oxide (nMgO) nanoparticles, in a model biodegradable polymer, namely poly (lacticcoglycolic acid) (PLGA), was studied. Highpower sonication was integrated with dual asymmetric centrifugal (DAC) mixing to improve dispersion of nanoparticles during solvent casting. The polymer/solvent ratio was optimized to improve nanoparticle dispersion in the multistep processing, including enhancing the efficacy of sonication and DAC mixing and reducing nanoparticle sedimentation during solventcasting. Microstructural characterization confirmed that this new process improved nanoparticle dispersion in nMgO/PLGA and nHA/PLGA nanocomposites. Improved nanoparticle dispersion increased the optical transparency visually and optical transmission quantitatively for both nHA/PLGA and nMgO/PLGA nanocomposites. Improved dispersion of nanoparticles improved the adhesion of bone marrow derived mesenchymal stem cells (BMSCs) on nHA/PLGA but decreased BMSC viability on nMgO/PLGA. This difference is likely because the chemistry of nHA and nMgO had different effects on BMSCs. This study provided a new process for enhancing dispersion of ceramic nanoparticles in a polymer matrix and revealed the effects of dispersion on optical properties and cell responses, which are valuable for engineering optimal ceramic/polymer nanocomposites for different biomedical applications.”

BPCR conference (August 29, 2018 9AM - 4PM: Kurz Purdue Technology Center, West Lafayette, IN) is a free, 1-day scientific-networking conference hosted by Akina, Inc. See more BPCRconference.com

PCL from PolySciTech used in the study of myelination process as part of development of repair mechanisms for neural injuries

Monday, June 18, 2018, 9:10 PM ET

Myelination is the process of forming a myelin sheath around a nerve to allow nerve impulses to move more quickly. This must occur for neural tissues to heal missing or damaged connections and does not normally occur easily. This is one of the reasons why nerve damage, such as those caused by spinal cord injuries, is so difficult to heal. Recently, researchers at Nanyang Technological University (Singapore), and The University of Edinburgh (UK) used PCL (PolyVivo AP009) from PolySciTech (www.polyscitech.com) to develop a mesh for growing neural cells. By controlling the conditions and exposure to select RNA sequences, they were able to elucidate some of the processes which lead to Myelination. This research holds promise for improved healing of nerve damage which may be applicable to treating blindness, paralysis, and other nerve-damage based diseases. Read more: Ong, William, Junquan Lin, Marie E. Bechler, Kai Wang, Mingfeng Wang, and Sing Yian Chew. "Microfiber Drug/Gene Delivery Platform for Study of Myelination." Acta biomaterialia (2018). https://www.sciencedirect.com/science/article/pii/S1742706118303544

“Abstract: Our ability to rescue functional deficits after demyelinating diseases or spinal cord injuries is limited by our lack of understanding of the complex remyelination process, which is crucial to functional recovery. In this study, we developed an electrospun suspended poly(ε-caprolactone) microfiber platform to enable the screening of therapeutics for remyelination. As a proof of concept, this platform employed scaffold-mediated non-viral delivery of a microRNA (miR) cocktail to promote oligodendrocyte precursor cells (OPCs) differentiation and myelination. We observed enhanced OPCs differentiation when the cells were transfected with miR-219 and miR-338 on the microfiber substrates. Moreover, miRs promoted the formation of MBP+ tubular extensions around the suspended fibers, which was indicative of myelination, instead of flat myelin membranes on 2D substrates. In addition, OPCs that were transfected with the cocktail of miRs formed significantly longer and larger amounts of MBP+ extensions. Taken together, these results demonstrate the efficacy of this functional screening platform for understanding myelination. Statement of Significance: The lack of understanding of the complex myelination process has hindered the discovery of effective therapeutic treatments for demyelinating diseases. Hence, in vitro models that enable systematic understanding, visualization and quantification of myelination are valuable. Unfortunately, achieving reproducible in vitro myelination by oligodendrocytes (OLs) remains highly challenging. Here, we engineered a suspended microfiber platform that enables sustained non-viral drug/gene delivery to study OL differentiation and myelination. Sustained drug delivery permits the investigation of OL development, which spans several weeks. We show that promyelinogenic microRNAs promoted OL differentiation and myelination on this platform. Our engineered microfiber substrate could serve as a drug/gene screening platform and facilitate future translation into direct implantable devices for in vivo remyelination purposes. Keywords: Electrospinning, RNA interference, Non-viral gene delivery, Oligodendrocytes, Oligodendrocyte precursor cells, microRNA”

BPCR conference (August 29, 2018 9AM - 4PM: Kurz Purdue Technology Center, West Lafayette, IN) is a free, 1-day scientific-networking conference hosted by Akina, Inc. See more BPCRconference.com

Recent patent describes use of PLGA-PEG-Mal from PolySciTech for nanoparticle-based therapies

Wednesday, June 13, 2018, 9:33 PM ET

Theranostics is a field of research in cancer which focuses on developing techniques that both diagnose and treat cancer. One method of accomplishing this is putting agents which can be detected by fluorescence, ultrasound, or x-ray techniques along with active drugs in a targeted nanoparticle structure. Recently, researchers at the University of Nevada used mPEG-PLGA (PolyVivo AK051) and Mal-PEG-PLGA (Polyvivo AI075) from PolySciTech (www.polyscitech.com) to develop a nanoparticle system containing drugs and quantum dots. This technology holds promise to provide for improved therapy for cancer in the future. Read more: Zhu, Xiaoshan, and Violeta Demillo. "Composites and Compositions for Therapeutic Use and Methods of Making and Using The Same." U.S. Patent Application 15/872,763, filed June 7, 2018. http://www.freepatentsonline.com/y2018/0154024.html

“Abstract: Disclosed herein are embodiments of composites and compositions that can be used for therapeutic applications in vivo and/or in vitro. The disclosed composites can comprise cores having magnetic nanoparticles, quantum dots, or combinations thereof and zwitterionic polymeric coatings that facilitate solubility and bioconjugation. The compositions disclosed herein can comprise the composites and one or more biomolecules, drugs, or combinations thereof. Also disclosed herein are methods of making the composites, composite components, and methods of making quantum dots for use in the composites.”

BPCR conference (August 29, 2018 9AM - 4PM: Kurz Purdue Technology Center, West Lafayette, IN) is a free, 1-day scientific-networking conference hosted by Akina, Inc. See more BPCRconference.com

PLGA from PolySciTech used in development of therapeutic nanoparticle system for treatment of diabetes-associated breast cancer

Wednesday, June 6, 2018, 9:34 PM ET

There are many causes and factors involved with cancer growth. One factor is abnormal levels of sugar resultant from diabetes. Since cancer cells have unusual metabolism, diabetes can encourage cancer to form or exacerbate existing cancers. Recently, researchers working at Tongji University, Shanghai Jiao Tong University, Charles R. Drew University, University of North Texas, University of Texas at Arlington, Xavier University of Louisiana, California State University, and University of California used PLGA from PolySciTech (www.polyscitech.com) to create nanoparticles for delivering a novel therapeutic drug which targets cancer’s dependence on glucose. This research holds promise to provide for better strategies to treat diabetes-associated breast cancer. Read more: Ke Wu, Xiaoting Yu, Zhimin Huang, Donghui Zhu, Xianghua Yi, Ying-Li Wu, Qiongyu Hao, Kevin T. Kemp II, Yahya Elshimali, Roshni Iyer, Kytai Truong Nguyen, Shilong Zheng, Guanglin Chen, Qiao-Hong Chen, Guangdi Wang, Jaydutt V Vadgama, and Yong Wu. "Targeting of PP2Cδ by a small molecule C23 inhibits high glucose-induced breast cancer progression in vivo". Antioxidants and Redox Signaling DOI: 10.1089/ars.2017.7486 (https://www.liebertpub.com/doi/abs/10.1089/ars.2017.7486).

“Abstract: Aims: Epidemiologic evidence indicates that diabetes may increase risk of breast cancer (BC) and mortality in patients with cancer. The pathophysiological relationships between diabetes and cancer are not fully understood and personalized treatments for diabetes-associated BC are urgently needed. Results: We observed that high glucose (HG), via activation of nuclear phosphatase PP2Cδ, suppresses p53 function and consequently promotes BC cell proliferation, migration and invasion. PP2Cδ expression is higher in tumor tissues from BC patients with hyperglycemia than those with normoglycemia. The mechanisms underlying HG stimulation of PP2Cδ involve classical/novel PKCs activation and GSK3β phosphorylation. Reactive oxygen species (ROS)/NF-κB pathway also mediates HG induction of PP2Cδ. Furthermore, we identified a 1,5-diheteroarylpenta-1,4-dien-3-one (C23) as a novel potent PP2Cδ inhibitor with a striking cytotoxicity on MCF-7 cells through cell-based screening assay for growth inhibition and activity of a group of curcumin mimics. Besides directly inhibiting PP2Cδ activity, C23 blocks HG induction of PP2Cδ expression via HSP27 induction and subsequent ablation of ROS/NF-κB activation. C23 thus can significantly block HG-triggered inhibition of p53 activity, leading to the inhibition of cancer cell proliferation, migration and invasion. Additionally, hyperglycemia promotes BC development in diabetic nude mice and C23 inhibits the xenografted BC tumor growth. Conclusions and Innovation: Our findings elucidate mechanisms that may have contributed to diabetes-associated breast cancer progression and provide the first evidence to support the possible alternative therapeutic approach to breast cancer patients with diabetes.”

BPCR conference (August 29, 2018 9AM - 4PM: Kurz Purdue Technology Center, West Lafayette, IN) is a free, 1-day scientific-networking conference hosted by Akina, Inc. See more BPCRconference.com

CRS Presentation

Friday, June 1, 2018, 9:11 AM ET

John Garner will be presenting “Solvent-dependent PLGA solubility for separation of PLGAs with different lactide:glycolide ratios” at the #CRSNYC Annual Meeting & Exposition! Learn more here: bit.ly/2kB2juf

PLGA-PEG-Mal from PolySciTech used as part of oral exenatide formulation development for diabetes treatment

Tuesday, May 29, 2018, 3:38 PM ET

Convenience is one of the often overlooked aspects of medical technology, however it is critical as convenience encourages patient compliance with medicinal regimens. Naturally, patients prefer oral formulations over injected formulations. Some medicines, however, have very poor absorption from the GI tract, which limits their ability to be administered by this route. Exenatide, a drug which treats diabetes, is one example of a poorly absorbed medicine. Recently, researchers at Binzhou Medical University, Yantai University, and Luye Pharmaceutical Co. (China) used PLGA-PEG-Maleimide (PolyVivo AI020) and mPEG-PLGA (PolyVivo AK037) from PolySciTech (www.polyscitech.com) to generate nanoparticles to cross the intestinal barrier to improve the oral bioavailability of exanatide. This research holds promise to offer an oral therapy for diabetes. Read more: Zhang, Liping, Yanan Shi, Yina Song, Xinfeng Sun, Xuemei Zhang, Kaoxiang Sun, and Youxin Li. "The use of low molecular weight protamine to enhance oral absorption of exenatide." International Journal of Pharmaceutics (2018). https://www.sciencedirect.com/science/article/pii/S0378517318303648

“Abstract: Although oral delivery of exenatide has significant advantages, its poor permeability through intestinal epithelial membranes and rapid digestion by pepsin and ereptase in the gastrointestinal tract make effective oral delivery of exenatide a formidable challenge. In this study, we constructed a zinc ion (Zn2+) and exenatide complex functionalized nanoparticle (NP) oral delivery system to overcome the above-mentioned issue. Polyethylene glycol-poly(lactic-co-glycolic acid) (PEG-PLGA) was used as a drug carrier to escape enzymatic degradation in the gastrointestinal tract, and low molecular weight protamine (LMWP) was used as a functional group to increase penetration of NPs into the intestinal epithelium. The functionalized NPs exhibited significantly improved penetration across the intestinal epithelium, as shown by cell uptake and transmembrane transport experiments. Moreover, a significant hypoglycemic effect was observed in diabetic rats. The relative bioavailability of the orally administered functionalized NPs vs. subcutaneous injection was 7.44%, 29-fold that of the exenatide-Zn2+ solution group. These findings indicate that our modification could effectively improve exenatide treatment. Keywords: Low molecular weight protamine PEG-PLGA Functionalized nanoparticle Exenatide-Zn2+ Oral delivery”

BPCR conference (August 29, 2018 9AM - 4PM: Kurz Purdue Technology Center, West Lafayette, IN) is a free, 1-day scientific-networking conference hosted by Akina, Inc. See more BPCRconference.com

Memorial Day

Sunday, May 27, 2018, 7:39 AM ET

Akina, Inc. (www.akinainc.com) Will be closed for Memorial Day May 28, 2018. We will resume normal business the following day.

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


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