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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Website temporarily down

Saturday, October 20, 2018, 8:45 PM ET

October 20, 2018: akinainc.com and affiliated sites are down temporarily due to heavy winds in Indiana creating communications and power issues. We hope to have the issue resolved shortly.

mPEG-PLGA from PolySciTech used in research on immune checkpoint inhibitors for cancer therapy

Friday, October 19, 2018, 4:50 PM ET

One of the insidious features of cancer is that it has the ability to prevent the immune system from recognizing the diseased cells as ‘non-self.’ Immune checkpoint inhibitors, as chemotherapeutics, act to eliminate this feature of cancer and enable the immune system to attack it. Recently, researchers from Harvard Medical School, Hamad Bin Khalifa University (Qatar), and University of California, Los Angeles, used mPEG-PLGA (PolyVivo AK102) from PolySciTech (www.polyscitech.com) to develop anti-PD-1 loaded nanoparticles and investigated the effect of these nanoparticles on cancer therapy. This research holds promise for better understanding of immunotherapy cancer treatment options. read more: Farideh Ordikhani, Mayuko Uehara, Vivek Kasinath, Li Dai, Siawosh K. Eskandari, Baharak Bahmani, Merve Yonar, Jamil R. Azzi, Yousef Haik, Peter T. Sage, George F. Murphy, Nasim Annabi, Tobias Schatton, Indira Guleria, and Reza Abdi “Targeting antigen-presenting cells by anti–PD-1 nanoparticles augments antitumor immunity” JCI Insight. 2018;3(20):e122700 https://insight.jci.org/articles/view/122700

“Recent studies in cancer research have focused intensely on the antineoplastic effects of immune checkpoint inhibitors. While the development of these inhibitors has progressed successfully, strategies to further improve their efficacy and reduce their toxicity are still needed. We hypothesized that the delivery of anti–PD-1 antibody encapsulated in PLGA nanoparticles (anti–PD-1 NPs) to the spleen would improve the antitumor effect of this agent. Unexpectedly, we found that mice treated with a high dose of anti–PD-1 NPs exhibited significantly higher mortality compared with those treated with free anti–PD-1 antibody, due to the overactivation of T cells. Administration of anti–PD-1 NPs to splenectomized LT-α–/– mice, which lack both lymph nodes and spleen, resulted in a complete reversal of this increased mortality and revealed the importance of secondary lymphoid tissues in mediating anti–PD-1–associated toxicity. Attenuation of the anti–PD-1 NPs dosage prevented toxicity and significantly improved its antitumor effect in the B16-F10 murine melanoma model. Furthermore, we found that anti–PD-1 NPs undergo internalization by DCs in the spleen, leading to their maturation and the subsequent activation of T cells. Our findings provide important clues that can lead to the development of strategies to enhance the efficacy of immune checkpoint inhibitors.”

PLGA-PEG-COOH from PolySciTech used in development of nucleolin-targeting nanoparticles

Wednesday, October 17, 2018, 4:50 PM ET

Often, in cancer, nucleolin is overexpressed on the surface which allows it to be used as a target for drug-delivery. Recently, researchers at Tabriz University of Medical Sciences (Iran) utilized PLGA-PEG-COOH (PolyVivo AI076) from PolySciTech (www.polyscitech.com) to generate anti-nucleolin decorated nanoparticles for cancer targeting. This research holds promise for improved chemotherapeutics. Read more: Mosafer, Jafar, and Ahad Mokhtarzadeh. "Cell Surface Nucleolin as a Promising Receptor for Effective AS1411 Aptamer-Mediated Targeted Drug Delivery into Cancer Cells." Current drug delivery 15, no. 9 (2018): 1323-1329. https://www.ingentaconnect.com/contentone/ben/cdd/2018/00000015/00000009/art00013

“Background: One of the major abundant proteins in the nucleous is nucleolin that overexpressed on the cytoplasmic membrane of malignant and endothelial cells and makes it as a promising condidate for targeted drug delivery. Objectives: In this study, doxorubicin (Dox) as a chemotherapy drug was entrapped into the Poly lacticco- glycolic acid (PLGA)-based nanoparticles (NPs). Then, the targeting ability of anti nucleolin AS1411 aptamer-targeted Dox-encapsulated PLGA-based NPs (AS1411-NPs) was investigated in high nucleolin-expressing C26 colon carcinoma and rat C6 glioma cell lines compared with low nucleolin expressing mouse L929 cell line. Methods: We recently first assessed the existence of cell surface nucleolin of these three different cell lines by immunocytochemistry method. We found that a large amount of nucleolin was localized in the cytoplasmic membrane of C26 and C6 cell lines, with a very smaller amount on the surface of L929 cell line. Results: As a result, more rapidly internalization of AS1411-NPs into the C26 and C6 cells compared with L929 cells was verified. Conclusion: We think that AS1411-NPs, as a ligand, first bind to nucleolin, as a receptor, and then the receptor-ligand complex is more efficiently incorporated into the high nucleolin-expressing cell lines through receptor-mediated endocytosis pathway. Keywords: AS1411 aptamer; Nucleolin; PLGA; doxorubicin; internalization; targeted delivery”

mPEG-PLGA and PLGA from PolySciTech used in development of nanoparticle therapy for brain cancer

Tuesday, October 16, 2018, 4:03 PM ET

Glioblastoma is a common form of brain cancer which is typically fatal. The treatment of cancer requires the use of medicines that typically have very severe side-effects and a very narrow therapeutic window. Recently, a kinase inhibitor has shown promise for cancer therapy, however, it failed due to toxicity issues during phase 1 clinical trials. The ability to deliver this molecule in a more controlled manner may reduce the toxicity issues and allow for it to be used as a therapy. Recently, researchers from the University of Massachusetts and the Dana-Farber Cancer Institute used mPEG-PLGA (AK027) and PLGA (AP041) from PolySciTech (www.polyscitech.com) to create nanoparticles loaded with a novel kinase inhibitor as a prototype therapy for brain-cancer. These nanoparticles allow for dosing smaller concentrations in a more time-controlled manner. This research holds promise to provide for improved therapies against this fatal disease. Read more: Velpurisiva, Praveena, Brandon Piel, Jack Lepine, and Prakash Rai. "GSK461364A, a Polo-Like Kinase-1 Inhibitor Encapsulated in Polymeric Nanoparticles for the Treatment of Glioblastoma Multiforme (GBM)." Bioengineering 5, no. 4 (2018): 83. http://www.mdpi.com/2306-5354/5/4/83

“Abstract: Glioblastoma Multiforme (GBM) is a common primary brain cancer with a poor prognosis and a median survival of less than 14 months. Current modes of treatment are associated with deleterious side effects that reduce the life span of the patients. Nanomedicine enables site-specific delivery of active pharmaceutical ingredients and facilitates entrapment inside the tumor. Polo-like kinase 1 (PLK-1) inhibitors have shown promising results in tumor cells. GSK461364A (GSK) is one such targeted inhibitor with reported toxicity issues in phase 1 clinical trials. We have demonstrated in our study that the action of GSK is time dependent across all concentrations. There is a distinct 15-20% decrease in cell viability via apoptosis in U87-MG cells dosed with GSK at low concentrations (within the nanomolar and lower micromolar range) compared to higher concentrations of the drug. Additionally, we have confirmed that PLGA-PEG nanoparticles (NPs) containing GSK have shown significant reduction in cell viability of tumor cells compared to their free equivalents. Thus, this polymeric nanoconstruct encapsulating GSK can be effective even at low concentrations and could improve the effectiveness of the drug while reducing side effects at the lower effective dose. This is the first study to report a PLK-1 inhibitor (GSK) encapsulated in a nanocarrier for cancer applications. Keywords: GSK461364A; Glioblastoma Multiforme; polymeric nanoparticles; cytotoxicity; enhanced permeability and retention; polo-like kinase inhibitor; oncology; oncomedicine; U-87 MG”

PLA-PEG-PLA thermogel from PolySciTech used in recent patent on ocular controlled-release system

Wednesday, October 10, 2018, 12:25 PM ET

Delivery of medications into the ocular region is necessary for a wide range of diseases, but also challenging. Recently, researchers for Biohealthways, Inc. used PLA-PEG-PLA thermogel (PolyVivo AK100) from PolySciTech (www.polyscitech.com) in development of patent technology for delivery of ocular medicines. This research holds promise to treat a wide range of ocular diseases. Read more: Pan, David. "Biodegrading implantable ocular sustained release drug delivery system." U.S. Patent Application 15/924,318, filed September 20, 2018 .https://patents.google.com/patent/US20180264179A1/en

“Abstract: An ocular implant is provided for an intraocular delivery of a therapeutic biologic agent. The implant may be used intracamerally or intravitreally. The implant may include a sustained-release biodegradable core and a biodegradable shell, wherein the shell has a longer biodegradable half-life than the core. The core may include a biodegradable gel medium, an active therapeutic biologic agent, and a biologic stabilizer. Upon insertion into the anterior chamber or vitreous body of an eye, the therapeutic biologic agent is released over an extended period, that may range from one day to one year. The therapeutic biologic agent may be, for example, tissue-plasminogen activator, an anti-VEGF agent, or another biopharmaceutical. The biodegradable implant may completely dissolve after implantation and need not be removed.”

300th article! Mal-PEG-PLGA and mPEG-PLGA from PolySciTech used in development of immune-targeting nanoparticles to reduce organ rejection

Wednesday, October 10, 2018, 12:18 PM ET

Organ transplantation is a life-saving surgical technique in which the organs or tissues from a donor can be placed into a recipient to replace damaged or missing organs. Organ rejection occurs when the recipient’s immune system recognizes the transplanted organs or tissue as ‘non-self’ and launches an immune response against them. Recently researchers at Johns Hopkins University School of Medicine, Harvard Medical School, Tufts University, Universite de Lille (France), Hamad bin Khalifa University (Qatar), and University of Maryland used mPEG-PLGA (AK102) and Mal-PEG-PLGA (A110) from PolySciTech (www.polyscitech.com) to develop targeted nanoparticles to prevent immune-rejection of the transplanted tissue. This technology holds promise to prevent the potentially fatal incidence of tissue rejection. Furthermore, this article officially marks the 300th publication citing PolySciTech as the source of their research products since the first article published in 2011. Read more: Bahmani, Baharak, Mayuko Uehara, Liwei Jiang, Farideh Ordikhani, Naima Banouni, Takaharu Ichimura, Zhabiz Solhjou et al. "Targeted delivery of immune therapeutics to lymph nodes prolongs cardiac allograft survival." The Journal of clinical investigation 128, no. 11 (2018). https://www.jci.org/articles/view/120923

“The targeted delivery of therapeutic drugs to lymph nodes (LNs) provides an unprecedented opportunity to improve the outcomes of transplantation and immune-mediated diseases. The high endothelial venule is a specialized segment of LN vasculature that uniquely expresses peripheral node addressin (PNAd) molecules. PNAd is recognized by MECA79 mAb. We previously generated a MECA79 mAb–coated microparticle (MP) that carries tacrolimus. Although this MP trafficked to LNs, it demonstrated limited therapeutic efficacy in our transplant model. Here, we have synthesized a nanoparticle (NP) as a carrier of anti-CD3, and optimized the conjugation strategy to coat the NP surface with MECA79 mAb (MECA79-anti-CD3-NP) to enhance LN accumulation. As compared with nonconjugated NPs, a significantly higher quantity of MECA79-NPs accumulated in the draining lymph node (DLN). Many MECA79-NPs underwent internalization by T cells and dendritic cells within the LNs. Short-term treatment of murine cardiac allograft recipients with MECA79-anti-CD3-NP resulted in significantly prolonged allograft survival in comparison with the control groups. Prolonged graft survival following treatment with MECA79-anti-CD3-NP was characterized by a significant increase in intragraft and DLN Treg populations. Treg depletion abrogated the prolongation of heart allograft survival. We believe this targeted approach of drug delivery could redefine the methods of administering immune therapeutics in transplantation.”

PLA from PolySciTech used in investigation of enzymatic degradation of plastics

Wednesday, October 10, 2018, 12:13 PM ET

An environmental hazard which has been growing over the years is the accumulation of plastic waste. Since conventional plastics, such as polyethylene and polypropylene, do not degrade easily, they remain in the ocean and other places for a long time. Recently, researchers from University of Toronto utilized a series of PLA’s (AP005, AP004, AP047) from PolySciTech (www.polyscitech.com) to investigate the role of environmental enzymes in breaking down PLA, a potential replacement for other plastics which can biodegrade under environmental conditions. This research holds promise for improved degradability of polyesters to reduce environmental burdens. Read more: Hajighasemi, Mahbod, Anatoli Tchigvintsev, Boguslaw P. Nocek, Robert Flick, Ana Popovic, Tran Hai, Anna N. Khusnutdinova et al. "Screening and characterization of novel polyesterases from environmental metagenomes with high hydrolytic activity against synthetic polyesters." Environmental Science & Technology (2018). https://pubs.acs.org/doi/abs/10.1021/acs.est.8b04252

“Abstract: The continuous growth of global plastics production, including polyesters, has resulted in increasing plastic pollution and subsequent negative environmental impacts. Therefore, enzyme-catalyzed depolymerization of synthetic polyesters as a plastics recycling approach has become a focus of research. In this study, we screened over 200 purified uncharacterized hydrolases from environmental metagenomes and sequenced microbial genomes and identified at least 10 proteins with high hydrolytic activity against synthetic polyesters. These include the metagenomic esterases MGS0156 and GEN0105, which hydrolyzed polylactic acid (PLA), polycaprolactone, as well as bis(benzoyloxyethyl)-terephthalate. With solid PLA as a substrate, both enzymes produced a mixture of lactic acid monomers, dimers, and higher oligomers as products. The crystal structure of MGS0156 was determined at 1.95 Å resolution and revealed a modified α/β hydrolase fold, with a lid domain and highly hydrophobic active site. Mutational studies of MGS0156 identified the residues critical for hydrolytic activity against both polyester and monoester substrates, with two-times higher polyesterase activity in the MGS0156 L169A mutant protein. Thus, our work identified novel, highly active polyesterases in environmental metagenomes and provided molecular insights into their activity, thereby augmenting our understanding of enzymatic polyester hydrolysis.”

Fluorescent-PLGA and PLGA-PEG-Mal from PolySciTech used in development of gastric/colorectal-cancer targeting nanoparticles.

Monday, October 1, 2018, 7:21 PM ET

Cancer cells present a variety of surface proteins and markers which can be used to both differentiate them from normal, healthy cells as well as useful as targets for treating the cancer cell. In this way, the antibody counter-part to the surface marker can be conjugated to a nanoparticle making it selectively ‘sticky’ to the cancer cell. This is a powerful technique to improve the efficacy of drugs against cancer cells with less toxicity against healthy cells. Recently, researchers at Universidade do Porto, Universitário de Ciências da Saúde (Portugal), and Queen’s University Belfast (UK) used PLGA-FKR648 (PolyVivo AV015) and PLGA-PEG-Mal (PolyVivo AI110) from PolySciTech (www.polyscitech.com) to generate fluorescent, targeted nanoparticles for treatment of gastric and colorectal cancer. This research holds promise for improved therapies against this difficult to treat and often fatal disease. Read more: Kennedy, Patrick J., Flavia Sousa, Daniel Ferreira, Carla Pereira, Marika Nestor, Carla Oliveira, Pedro L. Granja, and Bruno Sarmento. "Fab-conjugated PLGA nanoparticles effectively target cancer cells expressing human CD44v6." Acta Biomaterialia (2018). https://www.sciencedirect.com/science/article/pii/S1742706118305725

“Abstract: Targeting of CD44 isoforms containing exon v6 (CD44v6) represents a viable strategy for the therapy and/or early diagnosis of metastatic cancers of the epithelium (e.g. gastric and colorectal cancer). We developed and characterized for the first time poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles (NPs) modified with polyethylene glycol (PEG) and engrafted, by site-directed conjugation, with an engineered human Fab that specifically target human CD44v6 (v6 Fab-PLGA NPs). The v6 Fab-PLGA NPs display spherical morphology around 300 nm and are negatively charged. They strongly bound to a CD44v6-derived peptide and, more importantly, to cells that endogenously and exogenously express CD44v6, but not to non-expressing cells and cells expressing the standard isoform of CD44. The v6 Fab-PLGA NPs also recognized CD44v6 in tumor sections from cells grown subcutaneously within mice. The NPs had nominal cytotoxicity at 50 µg/mL and withstood simulated intestinal fluid exposure. Interestingly, v6 Fab-PLGA NPs cryopreserved in 10% trehalose and long-term stored maintained specific cell binding. In conclusion, we envision NPs targeting CD44v6 as potential in vivo diagnostic agents and/or as anti-cancer agents in patients previously stratified with CD44v6+ carcinomas. Statement of Significance: The v6 Fab-PLGA NPs displayed many favorable qualities as a potential CD44v6-targeted drug and/or diagnostic delivery agent. The NPs were designed for optimal ligand orientation and for immediate administration into humans. NPs strongly bind to cells that endogenously and exogenously express CD44v6, but not to non-expressing cells and cells expressing the standard isoform of CD44. Binding ability was retained after freeze-drying and long-term storage, providing evidences, for the first time, on the stability of Fab-functionalized NPs. These NPs can potentially be used as an in vivo diagnostic from parenteral or oral/rectal administration. Keywords: Human CD44v6 Targeted drug delivery Antibody-conjugated nanoparticles PLGA nanoparticles Theranostics”

PLGA from PolySciTech used in development of blood-brain-barrier penetrating nanoparticle-based treatment of brain cancer

Thursday, September 27, 2018, 1:53 PM ET

Brain cancer is often deadly and very difficult to treat partially due to the presence of the blood-brain-barrier, which prevents medicine from crossing over into the brain cavity. One means of delivering drug into this region is to generate small particles bearing specific signaling moieties such as transferrin or cell-penetrating peptide which triggers the endothelial lining of the brain to allow the particles to pass. Recently, researchers at North Dakota State University used PLGA (Polyvivo AP022) from PolySciTech (www.polyscitech.com) as part of their development of custom liposomal nanoparticles to deliver chemotherapeutic agents across the blood-brain-barrier. This research holds promise for improved therapies for brain-cancer in the future. Read More: Lakkadwala, Sushant, and Jagdish Singh. "Co-delivery of Doxorubicin and Erlotinib through Liposomal Nanoparticles for Glioblastoma Tumor Regression Using an In Vitro Brain Tumor Model." Colloids and Surfaces B: Biointerfaces (2018). https://www.sciencedirect.com/science/article/pii/S0927776518306581

“Abstract: Glioma is a highly malignant tumor that starts in the glial cells of brain. Tumor cells reproduce quickly and infiltrate rapidly in high grade glioma. Permeability of chemotherapeutic agents into brain is restricted owing to the presence of blood brain barrier (BBB). In this study, we developed a dual functionalized liposomal delivery system for efficient transport of chemotherapeutics across BBB for the treatment of glioma. Liposomes were surface modified with transferrin (Tf) for receptor targeting, and cell penetrating peptide PFVYLI (PFV) to increase translocation of doxorubicin (Dox) and Erlotinib (Erlo) across the BBB into glioblastoma (U87) tumor cells. In vitro cytotoxicity and hemolysis studies were performed to assess biocompatibility of liposomal nanoparticles. Cellular uptake studies demonstrated efficient internalization of Dox and Erlo in U87, brain endothelial (bEnd.3), and glial cells. In addition, dual functionalized liposomes showed significantly (p < 0.05) higher apoptosis in U87 cells. Significantly (p < 0.05) higher translocation of dual functionalized liposomes across the BBB and delivering chemotherapeutic drugs to the glioblastoma tumor cells inside PLGA-Chitosan scaffold resulted in approximately 52% tumor cell death, using in vitro brain tumor model. Highlights: Transferrin-PFVYLI (Tf-PFV) liposomes were prepared by post-insertion method. Tf-PFV liposomes showed Tf receptor targeting and enhanced cell penetration. Cytotoxicity and hemolysis studies exhibited biocompatibility of the liposomes. Increased transport of Tf-PFV liposomes across the barrier into tumor-scaffold. Tf-PFV liposomes demonstrated excellent anti-tumor efficacy. Keywords: Dual-functionalized liposomes Glioblastoma In vitro brain tumor model Co-delivery Blood brain barrier”

PLGA-PEG-Mal from PolySciTech used in development of non-small cell lung cancer therapeutic nanoparticles

Monday, September 24, 2018, 8:45 PM ET

Microfluidic emulsification is a manufacturing technique which holds promise to enable rapid and robust generation of nanoparticles or micelles. Higher uniformity, size control, and drug loading can be achieved by this technique relative to conventional methods, such as emulsion or dialysis techniques. Recently, researchers from Tongji University (China) used Mal-PEG-PLGA (PolyVivo AI110) to create nanoparticles both by dialysis and microfluidic techniques. These particles were targeted by conjugating on RGD ligands and the resultant particles were tested for loading, size, and targeting capabilities. This research holds promise to provide for improved cancer therapeutics in the future. Read more: Bao, Yuchen, Qinfang Deng, Yongyong Li, and Songwen Zhou. "Engineering docetaxel-loaded micelles for non-small cell lung cancer: a comparative study of microfluidic and bulk nanoparticle preparation." RSC Advances 8, no. 56 (2018): 31950-31966. https://pubs.rsc.org/en/content/articlehtml/2018/ra/c8ra04512g

“Abstract: Bulk preparation of micelles has the drawbacks of facile formation of large aggregates and heterogeneous particle size distribution. Microfluidic technology has shown clear potential to address these challenges for robust nanomedicine applications. In this study, docetaxel-loaded PLGA-PEG-Mal-based micelles were prepared by microfluidics and dialysis methods and their physicochemical properties were analyzed. The biological behaviors of these micelles were also investigated in the non-small cell lung cancer (NSCLC) cell line A549 in vitro as well as in vivo. Encouragingly, the mean particle size of the micelles prepared by microfluidics (DMM) was smaller, with an average size of 72 ± 1 nm and a narrow size distribution with a polydispersity index (PDI) of 0.072; meanwhile, micelles prepared by the dialysis method (DMD) had larger particle sizes (range, 102 to 144 nm) and PDIs (up to 0.390). More importantly, significantly high drug loading was achieved using the microfluidic process. The IC50 value of DMM was lower than that of DMD. Whole-body fluorescence imaging of live mice showed that DMM achieved higher accumulation in tumors compared with DMD. DMM showed superior antitumor efficacy, with a tumor inhibition rate of 91.5%. Moreover, pathological histology analysis revealed that no evident biological toxicity was caused by the micelles. In addition, Arg-Gly-Asp (RGD) was employed as a targeting agent on the basis of DMM to prepare targeting micelles, and the targeting micelles exhibited stronger cytotoxicity and obvious antitumor efficacy. In conclusion, DMM may have obvious clinical advantages for the treatment of NSCLC due to its optimized physiochemical properties. Therefore, microfluidic technology-based micelles are a promising platform as an effective drug delivery system for incorporating anticancer agents.”

mPEG-PLGA from PolySciTech used to create peptide-loaded nanoparticles to prevent bacterial biofilm

Tuesday, September 18, 2018, 9:16 PM ET

One of the problematic features of bacteria in the oral cavity is their tendency to adhere strongly to one another forming surfaces known as ‘biofilm.’ Biofilm is comprised of layers of bacteria all attached to one another that is very difficult to treat or remove. Recently, researchers at The University of Louisville used mPEG-PLGA (Polyvivo AK026) from PolySciTech (www.polyscitech.com) to create BAR peptide loaded nanoparticles that prevent bacteria from sticking to one another. These particles were found to be effective at preventing biofilm formation. This research holds promise to improve periodontal treatments. Read more: Mahmoud, Mohamed Y., Donald R. Demuth, and Jill M. Steinbach-Rankins. "BAR-encapsulated nanoparticles for the inhibition and disruption of Porphyromonas gingivalis–Streptococcus gordonii biofilms." Journal of Nanobiotechnology 16, no. 1 (2018): 69. https://link.springer.com/article/10.1186/s12951-018-0396-4

“Abstract: Background: Porphyromonas gingivalis adherence to oral streptococci is a key point in the pathogenesis of periodontal diseases (Honda in Cell Host Microbe 10:423–425, 2011). Previous work in our groups has shown that a region of the streptococcal antigen denoted BAR (SspB Adherence Region) inhibits P. gingivalis/S. gordonii interaction and biofilm formation both in vitro and in a mouse model of periodontitis (Daep et al. in Infect Immun 74:5756–5762, 2006; Daep et al. in Infect immun 76:3273–3280, 2008; Daep et al. in Infect Immun 79:67–74, 2011). However, high localized concentration and prolonged exposure are needed for BAR to be an effective therapeutic in the oral cavity. Methods: To address these challenges, we fabricated poly(lactic-co-glycolic acid) (PLGA) and methoxy-polyethylene glycol PLGA (mPEG-PLGA) nanoparticles (NPs) that encapsulate BAR peptide, and assessed the potency of BAR-encapsulated NPs to inhibit and disrupt in vitro two-species biofilms. In addition, the kinetics of BAR-encapsulated NPs were compared after different durations of exposure in a two-species biofilm model, against previously evaluated BAR-modified NPs and free BAR. Results: BAR-encapsulated PLGA and mPEG-PLGA NPs potently inhibited biofilm formation (IC50 = 0.7 μM) and also disrupted established biofilms (IC50 = 1.3 μM) in a dose-dependent manner. In addition, BAR released during the first 2 h of administration potently inhibits biofilm formation, while a longer duration of 3 h is required to disrupt pre-existing biofilms. Conclusions These results suggest that BAR-encapsulated NPs provide a potent platform to inhibit (prevent) and disrupt (treat) P. gingivalis/S. gordonii biofilms, relative to free BAR. Keywords Polymer nanoparticle Poly(lactic-co-glycolic acid) Peptide delivery Drug delivery Porphyromonas gingivalis Streptococcus gordonii Periodontal disease Oral biofilm”

PLCL and PLGA-NH2 from PolySciTech used in development of cartilage repair tissue scaffold

Tuesday, September 18, 2018, 9:14 PM ET

Cartilage heals poorly as it is poorly vascularized, grows slowly, and has critical mechanical properties. Cartilage is commonly damaged by arthritic disease and trauma. Recently, researchers from the University of Maryland and National Institute of Standards and Technology used PLCL (AP179) and PLGA-NH2 (AI125) from PolySciTech (www.polyscitech.com) to design a 3D printed scaffold for repairing cartilage. This technology holds promise for improved repair and healing of joint tissues. Read more: Guo, Ting, Maeesha Noshin, Hannah B. Baker, Evin Taskoy, Sean J. Meredith, Qinggong Tang, Julia P. Ringel et al. "3D Printed Biofunctionalized Scaffolds for Microfracture Repair of Cartilage Defects." Biomaterials (2018). https://www.sciencedirect.com/science/article/pii/S0142961218306598

“Abstract: While articular cartilage defects affect millions of people worldwide from adolescents to adults, the repair articular cartilage defects still remains challenging due to the limited endogenous regeneration of the tissue and poor integration with implantations. In this study, we developed a 3D-printed scaffold functionalized with aggrecan that supports the cellular fraction of bone marrow released from microfracture, a widely used clinical procedure, and demonstrated tremendous improvement of regenerated cartilage tissue quality and joint function in a lapine model. Optical coherence tomography (OCT) revealed doubled thickness of the regenerated cartilage tissue in the group treated with our aggrecan functionalized scaffold compared to standard microfracture treatment. H&E staining showed 366 ± 95 chondrocytes present in the unit area of cartilage layer with the support of bioactive scaffold, while conventional microfracture group showed only 112 ± 26 chondrocytes. The expression of type II collagen appeared almost 10 times higher with our approach compared to normal microfracture, indicating the potential to overcome the fibro-cartilage formation associated with current microfracture approach. The therapeutic effect was also evaluated at joint function level. The mobility was evaluated using a modified Basso, Beattie and Bresnahan (BBB) scale. While the defect control group showed no movement improvement over the course of study, all experimental groups showed a trend of increasing scores over time. The present work developed an effective method to regenerate critical articular defects by combining a 3D-printed therapeutic scaffold with the microfracture surgical procedure. This biofunctionalized acellular scaffold has great potential to be applied as a supplement for traditional microfracture to improve the quality of cartilage regeneration in a cost and labor effective way. Key Words: aggrecan scaffold extrusion 3D printing microfracture articular cartilage Poly(L-Lactide-co-ε-Caprolactone) custom fabrication”


Friday, September 14, 2018, 8:41 AM ET

Akina's website was down last night due to necessary repairs on our server. The website is back up and running now and we are business as usual. Thanks for your patience.

PEG-Folate from PolySciTech used in development of theranostic particle for breast cancer treatment

Monday, September 10, 2018, 8:33 PM ET

Theranostics refers to a method of treatment for cancer in which the applied therapy both treats and diagnosis the cancer. Typically, this relies on targeted nanoparticles which have specialized fluorescent properties in order to render cancer visible as well as deliver a therapeutic agent to the cancer cells to prevent their growth and proliferation. Recently, researchers at Wrocław University used Folate-PEG-NH2 (PolyVivo AE005) from PolySciTech (www.polyscitech.com) to develop theranostic nanoparticles against breast cancer. This research holds promise to provide for improved therapies against this difficult to treat and potentially fatal disease. Read more: Wawrzyńczyk, Dominika, Urszula Bazylińska, Łukasz Lamch, Julita Kulbacka, Anna Szewczyk, Artur Bednarkiewicz, Kazimiera Wilk, and Marek Samoć. "FRET Activated Processes in Smart Nanotheranostics Fabricated in a Sustainable Manner." ChemSusChem (2018). https://onlinelibrary.wiley.com/doi/abs/10.1002/cssc.201801441

“Abstract: The multilayer nanocarriers loaded with optically activated payloads are gaining increasing attention, due to their anticipated crucial role for providing new mechanisms of energy transfers in the health-oriented applications, as well as for energy storage and environment protection. The combination of careful selection of optical components for efficient Förster Resonance Energy Transfer, and surface engineering of the nanocarriers, allowed us to synthesize and characterize novel theranostic nanosystems for diagnosis and therapy of deep-seated tumors. The cargo, constrained within the oil core of the nanocapsules, composed of NaYF4:Tm+3,Yb+3 up-converting nanoparticles together with a second-generation porphyrin-based photosensitizing agent – Verteporfin, assured requisite diagnostic and therapeutic functions under near-infrared laser excitation. The outer polyaminoacid shell of the nanocapsules was functionalized with a ligand − poly(L-glutamic acid) functionalized by PEG-ylated folic acid − to ensure both “stealth” effect and active targeting towards human breast cancer cells. The preparation criteria of all nanocarriers building blocks meet the requirements for sustainable and green chemistry practices. The multifunctionality of the proposed nanocarriers is a consequence of both the surface functionalized organic exterior part, that was accessible for selective accumulation in cancer cells, and the hydrophobic optically active interior, which shows phototoxicity upon irradiation within the first biological window.”

PLGA from PolySciTech used in development of magnetic nanoparticles for brain cancer therapy

Wednesday, September 5, 2018, 12:02 PM ET

Have you ever pushed a magnet on one side of a table around using another magnet from beneath the table? If you have, it is unlikely you considered this as an option for treatment of brain cancer, however this is a technique which is being applied for crossing the notoriously difficult blood-brain-barrier. One of the insidious features of brain cancer is that the disease primarily occupies the ‘brain’ side of the blood-brain-barrier. Due to the limited uptake of medicines in the blood-stream into the brain, it is very difficult to administer therapeutics to brain cancer in patients. Recently, researchers at Iran University of Medical Sciences and University of Tehran (Iran) utilized PLGA (AP040) from PolySciTech (www.polyscitech.com) to create nano-graphene-oxide loaded nanoparticles with magnetic functionality. By carefully controlling magnetic fields, they were able to improve the particle capacity to deliver medicine across the blood-brain-barrier. This research holds promise for improved therapy for glioblastoma and other brain-cancer forms. Read more: Shirvalilou, Sakine, Samideh Khoei, Sepideh Khoee, Nida Jamali Raoufi, Mohammad Reza Karimi, and Ali Shakeri-Zadeh. "Development of a magnetic nano-graphene oxide Carrier for improved glioma-targeted drug delivery and imaging: In vitro and in vivo evaluations." Chemico-Biological Interactions (2018). https://www.sciencedirect.com/science/article/pii/S0009279718301601

“Abstract: To overcome the obstacles inflicted by the BBB in Glioblastoma multiforme (GBM) we investigated the use of Multifunctional nanoparticles that designed with a Nano-graphene oxide (NGO) sheet functionalized with magnetic poly (lactic-co-glycolic acid) (PLGA) and was used for glioma targeting delivery of radiosensitizing 5-iodo-2-deoxyuridine (IUdR). In vitro biocompatibility of nanocomposite has been studied by the MTT assay. In vivo efficacy of magnetic targeting on the amount and selectivity of magnetic nanoparticles accumulation in glioma-bearing rats under an external magnetic field (EMF) density of 0.5 T was easily monitored with MRI. IUdR-loaded magnetic NGO/PLGA with a diameter of 71.8 nm, a zeta potential of −33.07 ± 0.07 mV, and a drug loading content of 3.04 ± 0.46% presented superior superparamagnetic properties with a saturation magnetization (Ms) of 15.98 emu/g. Furthermore, Prussian blue staining showed effective magnetic targeting, leading to remarkably improved tumor inhibitory efficiency of IUdR. The tumor volume of rats after treatment with IUdR/NGO/SPION/PLGA + MF was decreased significantly compared to the rats treated with buffer saline, IUdR and SPION/IUdR/NGO/PLGA. Most importantly, our data demonstrate that IUdR/NGO/SPION/PLGA at the present magnetic field prolongs the median survival time of animals bearing gliomas (38 days, p < 0.01). Nanoparticles also had high thermal sensitivities under the alternating magnetic field. In conclusion, we developed magnetic IUdR/NGO/PLGA, which not only achieved to high accumulation at the targeted tumor site by magnetic targeting but also indicated significantly enhanced therapeutic efficiency and toxicity for glioma both in vitro and in vivo. This innovation increases the possibility of improving clinical efficiency of IUdR as a radiosensitizer, or lowering the total drug dose to decrease systemic toxicity. Graphical abstract: Schematic illustration of magnetic drug delivery, verified by staining and use as an MRI contrast agent with IUdR/GO/SPION/PLGA and MF. Highlights: IUdR-loaded magnetic NGO + MF indicated the strongest anticancer effects in rat gliomas. Magnetic NGO induces thermosensitising effects in alternative magnetic field. Magnetic NGO under external magnetic field could overcome the BBB. Magnetic NGO could enhance the MRI sensitivity. Magnetic NGO modified with PLGA showed sustained release of IUdR. Keywords: Superparamagnetic iron oxide Glioma Magnetic targeting 5-Iodo-2′-deoxyuridine Nano-graphene oxide”

You’re invited to the Biotech, Pharma, Cancer, Research (BPCR) Scientific Networking Meeting this Wednesday (8/29) at KPTC.

Monday, August 27, 2018, 11:04 AM ET

The first annual BPCR even will be held in the Kurz Purdue Technology Center from 9 AM to 4 PM as an opportunity to get out there, network, learn about companies in the area as well as meet with potential collaborators, customers, and investors. Event speakers include Anton Iliuk (Tymora), Rob Hill (Hatch 51), Kelvin Okamoto (Gen3Bio), Cedric D’Hue (D’Hue Law), Kyle Lutes (Delmar), Laura Downey (Concordance), Pete Kissinger (BASI), Ardian Wibowo (Helix) Joanne Zhane (Phytoption), Bill Ooms (BSS), and John Garner (Akina). The exhibit hall features 16 different companies including LyoHUB, Akanocure, PGC, Triclinic labs, BI, Purdue OTC, Zeblock, Miftek, and LSAI laboratories as well as several others. The event is free of charge and open to the public. See more at www.BPCRconference.com. We look forward to seeing you there.

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.

These posts are syndicated from John Garner's blog at http://jgakinainc.blogspot.com/ where you can post a question or comment. (Load took 5.8626520633698 seconds)


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