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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mPEG-PLGA/PLGA from PolySciTech used in development of dual-drug loaded nanoparticle-based brain-cancer therapy

Thursday, March 21, 2019, 4:16 PM ET

Glioblastoma is a form of brain cancer in which malignant glial cells spread to various areas of the brain. This form of cancer is very difficult to treat and requires specific manipulations of the biochemistry of the malignant cells to kill them. Gefitinib acts to dephosphorylate Bcl-2 associated death promoter (BAD) and GSK461364A induces cell cycle arrest at G2/M phase. Both of these mechanisms lead to apoptosis (cell death) and together these drugs can act synergistically to be potent treatment against cancer. Recently, researchers at University of Massachusetts Lowell utilized mPEG-PLGA (AK027) and PLGA (AP023) from PolySciTech (www.polyscitech.com) to create dual-loaded nanoparticles and tested these for use as a treatment against glioblastoma. This research holds promise to provide new therapeutic options against this lethal form of cancer. Read more: Velpurisiva, Praveena, and Prakash Rai. "Synergistic Action of Gefitinib and GSK41364A Simultaneously Loaded in Ratiometrically-Engineered Polymeric Nanoparticles for Glioblastoma Multiforme." Journal of Clinical Medicine 8, no. 3 (2019): 367. https://www.mdpi.com/2077-0383/8/3/367

“Abstract: Glioblastoma Multiforme is a deadly cancer of glial cells with very low survival rates. Current treatment options are invasive and have serious side effects. Single drug treatments make the tumor refractory after a certain period. Combination therapies have shown improvements in treatment responses against aggressive forms of cancer and are becoming a mainstay in the management of cancer. The purpose of this study is to design a combinatorial treatment regimen by engineering desired ratios of two different small molecule drugs (gefitinib and GSK461364A) in a single carrier that can reduce off-target effects and increase their bioavailability. Synergistic effects were observed with our formulation when optimal ratios of gefitinib and GSK461364A were loaded in poly (lactic-co-glycolic) acid and polyethylene glycol (PLGA-PEG) nanoparticles and tested for efficacy in U87-malignant glioma (U87-MG) cells. Combination nanoparticles proved to be more effective compared to single drug encapsulated nanoparticles, free drug combinations, and the mixture of two single loaded nanoparticles, with statistically significant values at certain ratios and drug concentrations. We also observed drastically reduced clonogenic potential of the cells that were treated with free drugs and nanoparticle combinations in a colony forming assay. From our findings, we conclude that the combination of GSK461364A and higher concentrations of gefitinib when encapsulated in nanoparticles yield synergistic killing of glioma cells. This study could form the basis for designing new combination treatments using nanoparticles to deliver multiple drugs to cancer cells for synergistic effects. Keywords: combination therapy; cancer; glioblastoma multiforme; polymeric nanoparticles; gefitinib; GSK461364A; drug resistance; synergistic effect; drug interaction; enhanced permeation and retention”

-Biotech, Pharma, Cancer, Research (BPCR) is a free, 1-day scientific networking conference hosted by Akina, Inc. on Aug 28, 2019. See more and register to attend at www.bpcrconference.com

Manuscript “Complex Sameness” From Akina, Inc.-FDA Research Highlights Q1/Q2 Assay Methodologies

Monday, March 18, 2019, 4:11 PM ET

In addition to providing polymer products through the PolySciTech product line, Akina, Inc. also provides analytical and research services through the Akinalytics division (http://www.akinalytics.com/). A recent publication relates the development work performed with the Food and Drug Administration to deconstruct microparticle formulations which are constructed of more than one type of PLGA (varying lactide ratio) by applying a series of semi-solvents which dissolve higher-lactide content PLGA sequentially so each fraction can be assayed. Trelstar ® 22.5 mg dose was deconstructed by this method and each fraction was assayed. This research holds promise to develop assays which enable determination of sameness between Reference-Listed Drug (RLD) and a proposed generic. Read more: Skidmore, Sarah, Justin Hadar, John Garner, Haesun Park, Kinam Park, Yan Wang, and Xiaohui Jiang. “Complex sameness: Separation of mixed poly (lactide-co-glycolide) s based on the lactide: glycolide ratio.” Journal of Controlled Release (2019). https://doi.org/10.1016/j.jconrel.2019.03.002 [Link for 50-Days of Free access (May 5, 2019): https://authors.elsevier.com/c/1YjxgcI2~p~xz]

“Abstract: Poly (lactide-co-glycolide) (PLGA) has been used for making injectable, long-acting depot formulations for the last three decades. An in depth understanding of PLGA polymers is critical for development of depot formulations as their properties control drug release kinetics. To date, about 20 PLGA-based formulations have been approved by the U.S. Food and Drug Administration (FDA) through new drug applications, and none of them have generic counterparts on the market yet. The lack of generic PLGA products is partly due to difficulties in reverse engineering. A generic injectable PLGA product is required to establish qualitative and quantitative (Q1/Q2) sameness of PLGA to that of a reference listed drug (RLD) to obtain an approval from the FDA. Conventional characterizations of PLGA used in a formulation rely on measuring the molecular weight by gel permeation chromatography (GPC) based on polystyrene molecular weight standards, and determining the lactide:glycolide (L: G) ratio by 1H NMR and the end-group by 13C NMR. These approaches, however, may not be suitable or sufficient, if a formulation has more than one type of PLGA, especially when they have similar molecular weights, but different L:G ratios. Accordingly, there is a need to develop new assay methods for separating PLGAs possessing different L:G ratios when used in a drug product and characterizing individual PLGAs. The current work identifies a series of semi-solvents which exhibit varying degrees of PLGA solubility depending on the L:G ratio of the polymer. A good solvent dissolves PLGAs with all L:G ratios ranging from 50:50 to 100:0. A semi-solvent dissolves PLGAs with only certain L:G ratios. Almost all semi-solvents identified in this study increase their PLGA solubility as the L:G ratio increases, i.e., the lactide content increases. This lacto-selectivity, favoring higher L:G ratios, has been applied for separating individual PLGAs in a given depot formulation, leading to analysis of each type of PLGA. This semi-solvent method allows a simple, practical bench-top separation of PLGAs of varying L:G ratios. This method enables isolation and identification of individual PLGAs from a complex mixture that is critical for the quality control of PLGA formulations, as well as reverse engineering for generic products to establish the Q1/Q2 sameness. Keywords: PLGA separation L:G ratio Trelstar Q1/Q2 sameness Long-acting depot”

PLGA-Rhodamine/PLGA from PolySciTech used in development of peptide-targeted nanoparticles to macrophages for cancer therapy

Monday, March 18, 2019, 11:46 AM ET

Cancer is not a homogenous mass of cells, rather it is a complex mixture of microenvironment and tissue. Several factors of the microenvironment act to promote the growth of the cancer tumor. One of these is the presence of tumor-associated macrophages (immune cells) which promote the growth of cancer cells by suppressing the local immune system as well as by other mechanisms. One target for cancer therapy is to prevent the mechanisms of these support cells thereby leaving cancer more vulnerable and reducing its growth and survival. Recently, researchers at Purdue University and Soochow University (China) used PLGA (AP031) and fluorescent PLGA-Rhodamine (AV011) from PolySciTech (www.polyscitec.com) to develop peptide-bound nanoparticles with selective uptake towards these macrophages. The fluorescent PLGA enables tracking the location of the nanoparticles as a means to confirm uptake. This research holds promise for the development of powerful and selective therapies against cancer. Read more: Pang, Liang, Yihua Pei, Gozde Uzunalli, Hyesun Hyun, L. Tiffany Lyle, and Yoon Yeo. "Surface Modification of Polymeric Nanoparticles with M2pep Peptide for Drug Delivery to Tumor-Associated Macrophages." Pharmaceutical Research 36, no. 4 (2019): 65. https://link.springer.com/article/10.1007/s11095-019-2596-5

“Purpose: Tumor-associated macrophages (TAMs) with immune-suppressive M2-like phenotype constitute a significant part of tumor and support its growth, thus making an attractive therapeutic target for cancer therapy. To improve the delivery of drugs that control the survival and/or functions of TAMs, we developed nanoparticulate drug carriers with high affinity for TAMs. Methods: Poly(lactic-co-glycolic acid) nanoparticles were coated with M2pep, a peptide ligand selectively binding to M2-polarized macrophages, via a simple surface modification method based on tannic acid-iron complex. The interactions of M2pep-coated nanoparticles with macrophages of different phenotypes were tested in vitro and in vivo. PLX3397, an inhibitor of the colony stimulating factor-1 (CSF-1)/CSF-1 receptor (CSF-1R) pathway and macrophage survival, was delivered to B16F10 tumors via M2pep-modified PLGA nanoparticles. Results: In bone marrow-derived macrophages polarized to M2 phenotype, M2pep-coated nanoparticles showed greater cellular uptake than those without M2pep. Consistently, M2pep-coated nanoparticles showed relatively high localization of CD206+ macrophages in B16F10 tumors. PLX3397 encapsulated in M2pep-coated nanoparticles attenuated tumor growth better than the free drug counterpart. Conclusion: These results support that M2pep-coating can help nanoparticles to interact with M2-like TAMs and facilitate the delivery of drugs that control the tumor-supportive functions of TAMs. KEY WORDS: Drug delivery M2pep PLGA nanoparticles PLX3397 tumor-associated macrophages”

-Biotech, Pharma, Cancer, Research (BPCR) is a free, 1-day scientific networking conference hosted by Akina, Inc. on Aug 28, 2019. See more and register to attend at www.bpcrconference.com

Thermogelling PLGA-PEG-PLGA from PolySciTech used in research of healing/scar-formation of cardiovascular tissue

Friday, March 15, 2019, 1:44 PM ET

The formation of scar tissue, or fibrosis, is a common response to injury and is part of the healing process of most tissues. Superficial scarring is benign however when it occurs in critical areas (such as cardiovascular tissue post balloon angioplasty) it can be lethal. Recently, researchers at The Ohio State University and University of Wisconsin used thermogelling PLGA-PEG-PLGA (AK012) from PolySciTech (www.polyscitech.com) to deliver centrinone-B (a PLK4 inhibitor) as part of modeling the effect that blocking PLK4 had on healing and scar formation. This research holds promise to aid in developing therapeutics to improve cardiovascular healing as part of treatment of atherosclerosis and hypertension. Read more: Jing Li, Go Urabe, Mengxue Zhang, Yitao Huang, Bowen Wang, Lynn Marcho, Hongtao Shen, K. Craig Kent, Lian-Wang Guo “A non-canonical role of polo-like kinase-4 in adventitial fibroblast cell type transition” bioRxiv (2019) 570267; doi: https://doi.org/10.1101/570267

“Abstract: Fibroblast-to-myofibroblast transition (FMT) is central to fibrosis. A divergent member of the polo-like kinase family, PLK4 is known for its canonical role in centriole duplication. Whether this mitotic factor regulates cell type transitions was underexplored. Here we investigated PLK4’s activation and expression and regulations thereof in platelet-derived growth factor (PDGF)- induced FMT of rat aortic adventitial fibroblasts. PLK4 inhibition (with centrinone-B or siRNA) diminished not only PDGF AA-induced proliferation/migration, but also smooth muscle a-actin and its transcription factor serum response factor’s activity. While PDGFR inhibition abrogated AA-stimulated PLK4 activation (phosphorylation) and mRNA/protein expression, inhibition of p38 downstream of PDGFR had a similar effect. Further, the transcription of PLK4 (and PDGFRa) was blocked by pan-inhibition of the bromo/extraterminal-domains chromatin-bookmark readers (BRD2, BRD3, BRD4), an effect herein determined via siRNAs as mainly mediated by BRD4. In vivo, periadventitial administration of centrinone-B reduced collagen content and thickness of the adventitia in a rat model of carotid artery injury. Thus, we identified a non-canonical role for PLK4 in FMT and its regulation by a BRD4/PDGFRa-dominated pathway. This study implicates a potential PLK4-targeted antifibrotic intervention. Keywords: PLK4, PDGF receptor-a, BRD4, fibroblast-to-myofibroblast transition, fibrosis”

- Biotech, Pharma, Cancer, Research (BPCR) is a free, 1-day scientific networking conference happening in Purdue Research Park Aug 28, 2019. See more and register to attend at www.bpcrconference.com

PLGA from PolySciTech used in development of new, large-scale nanoparticle manufacturing technique for drug-delivery applications

Wednesday, March 13, 2019, 4:16 PM ET

Nanoparticles are generated by carefully controlling the precipitation of polymers from a dissolved state to a solid state under reproducible conditions. Conventional methods to accomplish this, such as emulsion and dialysis, do not provide for highly uniform formation conditions. As such, these create a broad dispersity of nanoparticle sizes. Recent advances in microfluidics have enabled the generation of nanoparticles of uniform size however scalability remains a challenge. Recently, researchers at San Jose State University used PLGA (PolyVivo AP030) from PolySciTech (www.polyscitech.com) to develop a novel nanoparticle manufacturing technique based on a 3D-printed Multi-inlet vortex mixers with a specific herringbone design. This research holds promise to enable larger-scale manufacturing of nanoparticles. Read more: Bokare, Anuja, Ashley Takami, Jung Han Kim, Alexis Dong, Alan Chen, Ronald Valerio, Steven Gunn, and Folarin Erogbogbo. "Herringbone-Patterned 3D-Printed Devices as Alternatives to Microfluidics for Reproducible Production of Lipid Polymer Hybrid Nanoparticles." ACS Omega 4, no. 3 (2019): 4650-4657. https://pubs.acs.org/doi/abs/10.1021/acsomega.9b00128

“Major barriers to the implementation of nanotechnology include reproducible synthesis and scalability. Batch solution phase methods do not appear to have the potential to overcome these barriers. Microfluidic methods have been investigated as a means to enable controllable and reproducible synthesis; however, the most popular constituent of microfluidics, polydimethylsiloxane, is ill-suited for mass production. Multi-inlet vortex mixers (MIVMs) have been proposed as a method for scalable nanoparticle production; however, the control and reproducibility of the nanoparticle is wanting. Here, we investigate the ability to improve the control and reproducibility of nanoparticles produced by using 3D printed MIVMs with herringbone patterns in the flow channels. We compare three methods, viz., microfluidic, MIVM, and herringbone-patterned MIVM methods, for the synthesis of lipid–polymer hybrid nanoparticles (LPHNPs). The 3D printed herringbone-patterned MIVM method resulted in the smallest LPHNPs with the most uniform size distribution and shows more reproducible results as compared to the other two methods. To elucidate the mechanism underlying these results, concentration slices and vorticity streamlines of mixing chambers have been analyzed for 3D printed herringbone-patterned MIVM devices. The results bode well for LPHNPs, a formulation widely investigated for its improved therapeutic efficacy and biocompatibility. The herringbone-patterned device also has the potential to be broadly applied to many solution phase processes that take advantage of efficient mixing. The methods discussed here have broad implications for reproducible production of nanoparticles with constituents such as siRNA, proteins, quantum dots, and inorganic materials.”

- Biotech, Pharma, Cancer, Research (BPCR) is a free, 1-day scientific networking conference happening in Purdue Research Park Aug 28, 2019. See more and register to attend at www.bpcrconference.com

- Check out PolySciTech’s new “Getting Started” guide to find initial product suggestions based on your application. You can see this here http://polyscitech.com/_start/

Recent Patent describes use of PolySciTech thermogels for treatment of ocular fungal infection

Tuesday, March 12, 2019, 1:44 PM ET

Fungal keratitis is a common and debilitating corneal disease in horses, with the reported incidence in North America of approximately 25% in 2013. This disease can be treated with antifungal agents such as voriconazole, however efficacy from conventional drops is low due to rapid clearance of the drug from the eye by tear formation and other processes. Recently, researchers at University of Auburn filed a patent on the use of PLGA-PEG-PLGA thermogels (Polyvivo AK012, AK024, AK019) from PolySciTech (www.polyscitech.com) for a thermogel to aid in the delivery of voriconazole as part of ocular treatment of fungal diseases. This research holds promise to prevent this potentially blinding disease. Read more: Duran, Sue H., Allison Stewart, William R. Ravis, Eva Abarca-piedrafita, Rosemary Cuming, and Mariono MORA PEREIRA. "Sustained-release voriconazole-containing thermogel and uses thereof." U.S. Patent Application 16/117,443, filed February 28, 2019. https://patents.google.com/patent/US20190060312A1/en

“Abstract: The present disclosure provides veterinary formulations comprising a therapeutically effective amount of a voriconazole and a polymer. The disclosure also provides methods, and kits for the treatment of disease, such as for treating a fungal infection in an animal utilizing the veterinary formulations. The invention relates to veterinary formulations comprising a therapeutically effective amount of a voriconazole and a polymer. First, a sustained-release veterinary formulation comprising voriconazole has great potential to improve comfort and ultimate outcome for animals suffering from keratomycosis, especially horses. Second, such a formulation can provide a treatment which would be available to all affected animals, regardless of budget, as it could be administered in the field. Third, the formulation, given via subconjunctival injection, would negate the need for frequent topical application of voriconazole to animals. This would result in minimizing stress in patients and improving compliance by decreasing the volume, frequency, and cost of medication required for treatment. Fourth, utilization of thermogel polymers (e.g., thermosensitive biodegradable hydrogels or ‘thermogels’) can advantageously be administered as a liquid, followed by conversion to a gel deposit upon reaching the appropriate temperature. As a result, the thermogel polymers can maintain a sustained release of drug at the site of administration in the animal, for example over weeks to months. The sustained release of voriconazole to an animal suffering from keratomycosis would increase the local bioavailability of the medication, decrease systemic side effects, and improve client compliance.”

- Biotech, Pharma, Cancer, Research (BPCR) is a free, 1-day scientific networking conference happening in Purdue Research Park Aug 28, 2019. See more and register to attend at www.bpcrconference.com

- Check out PolySciTech’s new “Getting Started” guide to find initial product suggestions based on your application. You can see this here http://polyscitech.com/_start/

NEW: Product Application Starting Guide For PolySciTech Polymers

Thursday, March 7, 2019, 4:40 PM ET

In 2007 the PolyVivo product line started with eight simple block copolymers. Since that time, the catalog has grown to encompass over six-hundred products. From its inception, PolySciTech has put our customers in the driver’s seat of innovation. The majority of PolySciTech products are results from the multitude of customer requests we’ve received for new products over the years. The benefit from this is that the catalog is comprised of polymers which are in stock, rather than a listing of theoretical items which could be made by PolySciTech under request. The drawback is that the catalog listings are not organized along any particular pattern which makes navigating it challenging.

To assist customers with finding a polymer suggestion based on their application, we have created a ‘Getting Started Guide’ with helpful information and recommendations. This can be seen on our website here https://akinainc.com/polyscitech/_start/

PLGA-PEG-Mal from PolySciTech used in development of Saporin-loaded Nanoparticle for HER2+ Breast Cancer Therapy

Tuesday, March 5, 2019, 11:36 AM ET

Human epidermal growth factor receptor 2 (HER2) is a specific marker which is over-expressed on certain types of breast cancer and provides an opportunity for targeting nanoparticles towards the tumor cells. Similar to ricin toxin, saporin inactivates a cells ability to synthesize proteins which ultimately leads to the cells death. Unlike ricin, however, saporin has no inherent mechanism to actually enter a cell and as such presents no toxicity unless a specific mechanism is provided for it to enter the cell. Recently, researchers at Utrecht University (Netherlands) used PLGA-PEG-Mal (AI020) from PolySciTech (www.polyscitech.com) in research to create targeted nanoparticles which bind to HER2 marker on breast cancer and used photochemical delivery to introduce saporin into these cells leading to tumor death. This research holds promise to enable the treatment of highly metastatic and treatment-resistant forms of breast cancer. Read more: Martinez Jothar, Lucia, Nataliia Beztsinna, Cornelus F. van Nostrum, Wim E. Hennink, and Sabrina Oliveira. "Selective Cytotoxicity to HER2 Positive Breast Cancer Cells by Saporin-Loaded Nanobody-Targeted Polymeric Nanoparticles in Combination With Photochemical Internalization." Molecular Pharmaceutics. https://pubs.acs.org/doi/abs/10.1021/acs.molpharmaceut.8b01318

“In cancer treatment, polymeric nanoparticles (NPs) can serve as a vehicle for the delivery of cytotoxic proteins that have intracellular targets but that lack well-defined mechanisms for cellular internalization, such as saporin. In this work we have prepared PEGylated poly(lactic acid-co-glycolic acid-co-hydroxymethyl glycolic acid) (PLGHMGA) NPs for the selective delivery of saporin in the cytosol of HER2 positive cancer cells. This selective uptake was achieved by decorating the surface of the NPs with the 11A4 nanobody that is specific for the HER2 receptor. Confocal microscopy observations showed rapid and extensive uptake of the targeted NPs (11A4-NPs) by HER2 positive cells (SkBr3), but not by HER2 negative cells (MDA-MB-231). This selective uptake was blocked upon pre-incubation of the cells with an excess of nanobody. Non-targeted NPs (Cys-NPs) were not taken up by either type of cells. Importantly, a dose-dependent cytotoxic effect was only observed on SkBr3 cells when these were treated with saporin-loaded 11A4-NPs in combination with photochemical internalization (PCI), a technique that uses a photosensitizer and local light exposure to facilitate endosomal escape of entrapped nanocarriers and biomolecules. The combined use of saporin-loaded 11A4-NPs and PCI strongly inhibited cell proliferation and decreased cell viability through induction of apoptosis. Also the cytotoxic effect could be reduced by an excess of nanobody, reinforcing the selectivity of this system. These results suggest that the combination of the targeting nanobody on the NPs with PCI are effective means to achieve selective uptake and cytotoxicity of saporin-loaded NPs.”

- Interested in using polymers for drug-delivery, but looking for advice on which one to start with? Check out PolySciTech’s new “Getting Started” guide to narrow down some initial suggestions based on your application. You can see this here http://polyscitech.com/_start/

- Biotech, Pharma, Cancer, Research (BPCR) is a free, 1-day scientific networking conference happening in Purdue Research Park Aug 28, 2019. See more and register to attend at www.bpcrconference.com

PLGA from PolySciTech used in development of imaging technique for analysis of antibacterial coatings on orthopeadic implants.

Monday, March 4, 2019, 4:43 PM ET

Whenever an implant is surgically placed, there is always the potential for a bacterial infection to occur leading to an orthopedic implant-associated infection. One means to prevent this is to apply a biodegradable polymer coating which releases antibiotics from the implant to prevent the growth of bacteria in the area surrounding the implant. Recently, Researchers at Johns Hopkins University used PLGA (AP082, AP059) from PolySciTech (www.polyscitech.com) to provide for a model antibiotic-releasing implant coating to test an In vivo bioluminescence imaging technique for determining bacterial growth against. This research holds promise for improved development of bacterial-resistant implants to reduce the incidence of infection post-surgery. Read more: Miller, Robert J., John M. Thompson, Jesse Zheng, Mark C. Marchitto, Nathan K. Archer, Bret L. Pinsker, Roger V. Ortines et al. "In Vivo Bioluminescence Imaging in a Rabbit Model of Orthopaedic Implant-Associated Infection to Monitor Efficacy of an Antibiotic-Releasing Coating." JBJS 101, no. 4 (2019): e12. https://journals.lww.com/jbjsjournal/subjects/Oncology/Fulltext/2019/02200/In_Vivo_Bioluminescence_Imaging_in_a_Rabbit_Model.9.aspx

“Background: In vivo bioluminescence imaging (BLI) provides noninvasive monitoring of bacterial burden in animal models of orthopaedic implant-associated infection (OIAI). However, technical limitations have limited its use to mouse and rat models of OIAI. The goal of this study was to develop a larger, rabbit model of OIAI using in vivo BLI to evaluate the efficacy of an antibiotic-releasing implant coating. Methods: A nanofiber coating loaded with or without linezolid-rifampin was electrospun onto a surgical-grade locking peg. To model OIAI in rabbits, a medial parapatellar arthrotomy was performed to ream the femoral canal, and a bright bioluminescent methicillin-resistant Staphylococcus aureus (MRSA) strain was inoculated into the canal, followed by retrograde insertion of the coated implant flush with the articular surface. In vivo BLI signals were confirmed by ex vivo colony-forming units (CFUs) from tissue, bone, and implant specimens. Results: In this rabbit model of OIAI (n = 6 rabbits per group), implants coated without antibiotics were associated with significantly increased knee width and in vivo BLI signals compared with implants coated with linezolid-rifampin (p < 0.001 and p < 0.05, respectively). On day 7, the implants without antibiotics were associated with significantly increased CFUs from tissue (mean [and standard error of the mean], 1.4 × 108 ± 2.1 × 107 CFUs; p < 0.001), bone (6.9 × 106 ± 3.1 × 106 CFUs; p < 0.05), and implant (5.1 × 105 ± 2.2 × 105 CFUs; p < 0.05) specimens compared with implants with linezolid-rifampin, which demonstrated no detectable CFUs from any source. Conclusions: By combining a bright bioluminescent MRSA strain with modified techniques, in vivo BLI in a rabbit model of OIAI demonstrated the efficacy of an antibiotic-releasing coating. Clinical Relevance: The new capability of in vivo BLI for noninvasive monitoring of bacterial burden in larger-animal models of OIAI may have important preclinical relevance.”

Biotech, Pharma, Cancer, Research (BPCR) is a free, 1-day scientific networking conference happening in Purdue Research Park Aug 28, 2019. See more and register to attend at www.bpcrconference.com

Folate-PEG, PEG-PLLA polymers from PolySciTech used in development of targeted nanoparticle photodynamic therapy of cancer

Thursday, February 21, 2019, 9:04 PM ET

Cancer therapy suffers from drawbacks due to the non-specific nature of chemotherapy as well as the invasive nature of surgical and radiological means of treatment. Targeted therapies which primarily affect the cancerous tissue without damaging healthy tissue hold promise to reduce the side-effects of cancer treatment. Recently, researchers at Wroclaw University (Poland) used mPEG-PLLA (AK004) and Folate-PEG-COOH (AE003) from PolySciTech (www.polyscitech.com) to create targeted nanoparticles for phototherapy. This research holds promise to improve treatment regiments for cancers. Read more: Lamch, Łukasz, Julita Kulbacka, Magda Dubińska-Magiera, Jolanta Saczko, and Kazimiera A. Wilk. "Folate-directed zinc (II) phthalocyanine loaded polymeric micelles engineered to generate reactive oxygen species for efficacious photodynamic therapy of cancers." Photodiagnosis and Photodynamic Therapy (2019). https://www.sciencedirect.com/science/article/pii/S1572100019300304

“Highlights: Folate functionalized block copolymers were used for zinc (II) phthalocyanine encapsulation. ZnPc-loaded micelles of FA-PEG-b-PLLA (DH<150 a="" abstract:="" accomplished="" accumulation="" addition="" after="" an="" analysis="" and="" anticancer="" application="" are="" atomic="" attached="" attractive="" b-plla="" b-poly="" be="" becoming="" biocompatible="" biomedical="" block="" br="" by="" can="" cancer="" carcinoma="" cell="" cells.="" cellular="" chain="" chemical="" colloid="" con="" conjunction="" copolymer="" copolymers="" cyto-="" cytoskeletal="" cytoskeleton="" delivered="" delivery.="" delivery="" demonstrated="" derivative="" diameter="" diblock="" distribution="" drug="" drugs="" dynamic="" e45="" effect.="" effective="" effects="" efficacy="" efficiently="" end="" enhanced="" entrapped="" ethylene="" evaluated="" f-actin="" fa-nanomicelles="" fda-approved="" folate-functionalized="" folate="" for="" force="" functionalized="" generation="" good="" imaging="" improve="" in="" index="" induced="" internalized="" intracellular="" is="" it="" its="" keywords:="" lactide="" ligand="" light="" lines.="" low="" me45="" measurements="" melanoma="" metastatic="" methoxypoly="" micellar="" micelles="" microscopy="" molecules="" morphology.="" mpeg-b-plla="" nanocarriers="" nanomedicine="" nm="" normal="" npc="" of="" option="" our="" ovarian="" oxide="" oxygen="" pdt="" peg="" performed="" permeability="" photocytotoxicity="" photodynamic="" photosensitizer="" phthalocyanine="" physical="" polydispersity="" polymeric="" potential="" procedures="" promising="" reaction.="" reaction="" reactive="" reduce="" reorganization.="" reorganization="" resistant="" resulting="" results="" retention="" rmed="" ros="" scattering="" second="" selective="" showed="" side="" since="" size="" skov-3="" smart="" species="" specific="" stability.="" stability="" studied="" studies="" study="" surface="" targeted="" that="" the="" their="" therapy="" therefore="" tissues.="" to="" transport="" undergoing="" used="" using="" via="" visualized="" was="" we="" were="" while="" with="" zinc="" znpc-smart="">
Biotech, Pharma, Cancer, Research (BPCR) is a free, 1-day scientific networking conference happening in Purdue Research Park Aug 28, 2019. See more and register to attend at www.bpcrconference.com

PLGA from PolySciTech described in patent application as part of manufacturing of PLGA/PEI particles for stem-cell delivery

Thursday, February 21, 2019, 9:03 PM ET

Stem-cells hold promise to treat a wide variety of diseases including cardiovascular disease. Recently, PLGA (AP089) from PolySciTech (www.polyscitech.com) was described as part of a process of making PLGA-PEI particles for stem-cell delivery in a recent patent from researchers at University of Utah. This research holds promise for treating cardiovascular diseases. Read more: Kim, Sung Wan, Kwang Suk Lim, and Young Sook Lee. "Plga/pei particles and methods of making and using the same." U.S. Patent Application 16/068,302, filed February 7, 2019. https://patents.google.com/patent/US20190038558A1/en

“Abstract: Poly(lactic-co-glycolic acid)/polyethylenimine (PLGA/PEI) particles and methods directed to the preparation of PLGA/PEI particles are provided. Methods of using PLGA/PEI particles for the proliferation of stem cells and/or delivery of stem cells are also provided. For example, methods of treating a subject having, or at risk of developing, a cardiovascular disorder can include administering a therapeutically effective amount of stem cell-loaded PLGA/PEI particles to the subject.”

Biotech, Pharma, Cancer, Research (BPCR) is a free, 1-day scientific networking conference happening in Purdue Research Park Aug 28, 2019. See more and register to attend at www.bpcrconference.com

Website temporarily down 2-16-2019

Saturday, February 16, 2019, 4:05 PM ET

As of February 16, 2019, we are experiencing a loss of internet service to our location which is affecting our website (akinainc.com domain and affiliated sites). Thanks for your patience as we work to rectify this issue.

Biotech-Pharma-Cancer-Research (BPCR) Registration Now Open

Thursday, February 7, 2019, 4:29 PM ET

BPCR is a free, 1-day scientific Networking Conference which Akina, Inc. sponsors in the Purdue Research Park. This networking and scientific event allows for Purdue Research Park businesses, domestic research companies, and start-ups to meet with potential customers, investors and collaborators as well as, to get to know one another. There are open spots for Scientific Presentations (20 min) on research, Soapbox presentations on business opportunities (5 min), scientific poster session, as well as table-top displays for promotion and networking. see more and register at www.BPCRconference.com.

PolySciTech polymers used in recent patent regarding a new manufacturing technique to generate nanoparticles

Thursday, February 7, 2019, 4:20 PM ET

There are many different methods to generate nanoparticles and there are continuously new methods developed in this field. A recent patent by Phosphorex describes many PolySciTech (www.polyscitech.com) polymers for use in making nanoparticles including AV017 (mPEG-PLA-FKR648), AV18 (mPEG-PLGA-FKR560), AV016 (PLA-Fluorescein), AV013 (PLA-FPR648), AV015 (PLGA-FKR648), AV001 (PLGA-Fluorescein), AV006 (PLGA-FPI749), and AV011 (PLGA-Rhodamine B), AI016 (PLGA-NH2), AI025 (PLGA-SH), AI096 (PLGA-NHS), AI052 (PLGA-PEG-Mal), AI078 (PLGA-PEG-COOH), AI087 (PCL-NH2), AI021 (NH2-PLGA-NH2), AI086 (mPEG-PLGA-NH2). This research holds promise for further development of nanoparticle based technology. Read more: Wu, Bin. "Extremely small nanoparticles of degradable polymers." U.S. Patent Application 15/897,371, filed January 24, 2019. https://patents.google.com/patent/US20190021999A1/en

“Summary: The invention described herein is partly based on the realization that, to encapsulate a water-soluble drug, a double emulsion process is commonly used, which requires the polymer (e.g., PLGA polymer) to be dissolved in a water immiscible solvent, whereas the solvents used in the precipitation method are generally water miscible. Thus, to solve this problem, the current invention provides a method of synthesizing small polymeric nanoparticles by utilizing a single emulsion technique, described herein. This invention also provides a method of synthesizing small polymeric nanoparticles by utilizing a double emulsion technique, described herein. This invention also provides a method of synthesizing small polymeric nanoparticles loaded with therapeutic agents by utilizing a single emulsion technique, described herein. This invention also provides a method of synthesizing small polymeric nanoparticles loaded with therapeutic agents by utilizing a double emulsion technique, described herein. This invention also provides a composition of small polymeric nanoparticles, described herein. This invention also provides a composition of small polymeric nanoparticles loaded with therapeutic agents, described herein. This invention also provides a composition of small polymeric nanoparticles coated with non-therapeutic agents, described herein.”

Biotech, Pharma, Cancer, Research (BPCR) is a free, 1-day scientific networking conference happening in Purdue Research Park Aug 28, 2019. See more and register to attend at www.bpcrconference.com

PLA from PolySciTech used in development of biodegradable adhesives

Thursday, February 7, 2019, 4:19 PM ET

Most glues are petroleum based, which creates an environmental concern due to lack of degradation. One method to avoid this is to use adhesives which are generated from renewable resources. Recently, researchers at Purdue University used PLA (AP138) from PolySciTech (www.polyscitech.com) as part of research on high molecular-weight biodegradable adhesives. This research holds promise for improving adhesive performance in a wide-array of applications in an environmentally responsible manner. Read more: Siebert, Heather M., and Jonathan J. Wilker. "Improving the Molecular Weight and Synthesis of a Renewable Biomimetic Adhesive Polymer." European Polymer Journal (2019). https://www.sciencedirect.com/science/article/pii/S0014305718323681

“Highlights: A bio-based adhesive system is presented to provide an alternative to petroleum-derived glues. Improvements to the synthesis of this polymer system have been achieved. Bonding is shown to depend upon polymer molecular weight and dispersity. Abstract: Renewable materials are in demand to replace the petroleum-based glues we use on a daily basis. Such substitutions will not take place until bio-based adhesives can meet or exceed the performance of current materials. Work presented here examines several chemical parameters in order to improve the molecular weight and synthetic strategy for a polymer that combines polylactic acid with mussel mimicking catechol, (“catechol-PLA”). Altering the polymerization time as well as the deprotection time and temperature afforded better control over both molecular weights and yields. Dispersity and molecular weight were shown to both be parameters tunable to improve adhesion strength. Cross-linking with iron improved the adhesion of low molecular weight polymers, bringing performance up to that of the longer chain counterparts. Such cross-linking and molecular weight effects were seen to alter the balance of adhesive and cohesive interactions. Such development and understanding of renewable polymer systems may help to hasten future competition with petroleum-based adhesive”

Biotech, Pharma, Cancer, Research (BPCR) is a free, 1-day scientific networking conference happening in Purdue Research Park Aug 28, 2019. See more and register to attend at www.bpcrconference.com

Bezwada Biomedical Brand Polymers, on sale now at PolySciTech, used in research on improving shelf-life of food

Wednesday, February 6, 2019, 3:47 PM ET

In addition to providing in-house manufactured products, PolySciTech (www.polyscitech.com) also provides for distribution of products from high-quality research vendors, especially those who provide ‘hard-to-find’ and unique materials relevant to the biomedical field. A massive sale is going on now for Bezwada-Brand polymers including both Poly(ethylene glycol) di(meth)acrylate(s) (AEB001-AEB007) and polyesters including PCL’s, PLCL’s, PGACL’s, PDO’s, PLA’s, PTMCLA’s, PLGA’s, PDOLA’s, PTMC’s, and PDOGALA’s (APB001-APB038). For online purchasing, use coupon-code BEZWADA40 to receive an additional 40% discount at checkout for these polymers.

Recently, these polymers were used by researchers at the Indian Institute of Technology for research in food-preservation technology to provide for extended release of antioxidants and antibiotics to food. This research holds promise to improve the food supply by reducing spoilage. Read more: Biswal, Agni Kumar, and Sampa Saha. "Prolonging food shelf-life by dual actives release from multi-layered polymer particles." Colloids and Surfaces B: Biointerfaces 175 (2019): 281-290. https://www.sciencedirect.com/science/article/pii/S0927776518308841

“Highlights: Multilayered particles with antioxidant and antibacterial actives were fabricated in one step. Mechanism of tri-layered formation by using 2 polymers of varying viscosity was explained. Long term antibacterial and antioxidant activity were achieved from multi-layered particles. Abstract: Biodegradable polymer based 'controlled release packaging' technology has ability to release packaging actives in controlled manner to prolong the food shelf-life. Currently available systems are not sufficiently capable of releasing multiple actives in sustainable fashion. Hence, the purpose of this study was to develop dual actives (antioxidant and antibacterial) loaded multilayered microparticles in one step and to release them at rates suitable for long-term inhibition of bacterial growth as well as lipid oxidation in food. In order to achieve this goal, 2 kinds of multilayered polymer particles made up of PLLA (Poly(l-lactic acid)) and PLGA (Poly(dl-lactic-co-glycolic acid) with varying viscosity were developed using emulsion solvent evaporation method. Surprisingly, low viscous PLGA resulted tri-layered particles (PLGA/PLLA/PLGA: shell/middle/core) instead of bi-layered (PLGA/PLLA: shell/core) particles as observed for high viscous PLGA. The mechanism of formation of tri-layered particles was investigated in detail. The outermost layer consisted of relatively more hydrophilic polymer PLGA along with benzoic acid (antibacterial) and the inner core comprised of hydrophobic polymer PLLA and tocopherol (antioxidant). Release study demonstrated that release rate of dual actives were significantly accelerated from tri-layered particles in comparison to bi-layered one and their release profiles can be well explained with the help of Ridger-Peppas model. Both sets of particles exhibited long-term antibacterial (against both Escherichia coli and Staphylococcus aureus) as well as antioxidant effect over a period of 60 days. The results show for the first time the feasibility of using multilayered microparticles to prolong the food shelf-life by simultaneous release of multiple actives. Keywords: Multi-layer Biodegradable Polymer particles Controlled release Active packaging”

PEG-PLGAs and PLGA-Fluorescent polymers from PolySciTech used in development of concurrent Chemo-Immuno-Radiotherapy methodology for cancer treatment

Monday, February 4, 2019, 4:26 PM ET

Lymphoma is a form of cancer which affects immune cells within the human body causing them to grow in pathological ways. It is a very common, and often difficult to treat, form of cancer. Treatments for cancer can take many forms however there has been evidence that combining treatments of multiple types (e.g. chemotherapy and radiotherapy) can have an impact on the cancer which is greater than simply the additive effects of each type of therapy. Recently, researchers at University of North Carolina at Chapel Hill, SHAL Technologies, Inc., and Levine Cancer Institute utilized mPEG-PLGA (AK101), PLA-PEG-NHS (AI068), and PLGA-rhodamine (AV027) from PolySciTech (www.polyscitech.com) to generate doxorubicin-loaded nanoparticles decorated with Selective High-Affinity Ligands (SHAL) for targeting to lymphoma. By combining this nanoparticle therapy with other methods, such as radiotherapy, they were able to eradicate lymphoma at a success rate of 80% in a mouse model. This research holds promise to provide for improved cancer therapy against this common and difficult to treat form of cancer. Read more: Au, Kin Man, Rod Balhorn, Monique C. Balhorn, Steven I. Park, and Andrew Z. Wang. "High-Performance Concurrent Chemo-Immuno-Radiotherapy for the Treatment of Hematologic Cancer through Selective High-Affinity Ligand Antibody Mimic-Functionalized Doxorubicin-Encapsulated Nanoparticles." ACS Central Science (2019). https://pubs.acs.org/doi/abs/10.1021/acscentsci.8b00746

“Abstract: Non-Hodgkin lymphoma is one of the most common types of cancer. Relapsed and refractory diseases are still common and remain significant challenges as the majority of these patients eventually succumb to the disease. Herein, we report a translatable concurrent chemo-immuno-radiotherapy (CIRT) strategy that utilizes fully synthetic antibody mimic Selective High-Affinity Ligand (SHAL)-functionalized doxorubicin-encapsulated nanoparticles (Dox NPs) for the treatment of human leukocyte antigen-D related (HLA-DR) antigen-overexpressed tumors. We demonstrated that our tailor-made antibody mimic-functionalized NPs bound selectively to different HLA-DR-overexpressed human lymphoma cells, cross-linked the cell surface HLA-DR, and triggered the internalization of NPs. In addition to the direct cytotoxic effect by Dox, the internalized NPs then released the encapsulated Dox and upregulated the HLA-DR expression of the surviving cells, which further augmented immunogenic cell death (ICD). The released Dox not only promotes ICD but also sensitizes the cancer cells to irradiation by inducing cell cycle arrest and preventing the repair of DNA damage. In vivo biodistribution and toxicity studies confirm that the targeted NPs enhanced tumor uptake and reduced systemic toxicities of Dox. Our comprehensive in vivo anticancer efficacy studies using lymphoma xenograft tumor models show that the antibody-mimic functional NPs effectively inhibit tumor growth and sensitize the cancer cells for concurrent CIRT treatment without incurring significant side effects. With an appropriate treatment schedule, the SHAL-functionalized Dox NPs enhanced the cell killing efficiency of radiotherapy by more than 100% and eradicated more than 80% of the lymphoma tumors.”

mPEG-PLGA from PolySciTech used in investigation on nanoparticle interactions with the lymphatic system

Monday, February 4, 2019, 4:25 PM ET

One method to provide for improved vaccines with high potency is to target the delivery system to enable maximum exposure to immune cells. A strategy to accomplish this is to generate nanoparticles which are designed to be uptaken by the lymph nodes for good exposure to lymphocyte cells. The interactions between nanoparticles and cells are driven by many factors including biochemical (charge, specific interactions) and physical (size) parameters. Recently, researchers working at Johns Hopkins University, Yale University, and University of Florida used PEG-PLGA (AK101) from PolySciTech (www.polyscitech.com) to investigate nanoparticle movement in respect to the lymphatic system relative to nanoparticle size. This research holds promise to provide further understanding of how particles interact with living bodies to enable development of advanced drug-delivery particles for vaccines. Read more: Howard, Gregory P., Garima Verma, Xiyu Ke, Winter M. Thayer, Timothy Hamerly, Victoria K. Baxter, John E. Lee, Rhoel R. Dinglasan, and Hai-Quan Mao. "Critical size limit of biodegradable nanoparticles for enhanced lymph node trafficking and paracortex penetration." Nano Research: 1-8. https://link.springer.com/article/10.1007/s12274-019-2301-3

“Abstract: Lymph node (LN) targeting through interstitial drainage of nanoparticles (NPs) is an attractive strategy to stimulate a potent immune response, as LNs are the primary site for lymphocyte priming by antigen presenting cells (APCs) and triggering of an adaptive immune response. NP size has been shown to influence the efficiency of LN-targeting and retention after subcutaneous injection. For clinical translation, biodegradable NPs are preferred as carrier for vaccine delivery. However, the selective “size gate” for effective LN-drainage, particularly the kinetics of LN trafficking, is less well defined. This is partly due to the challenge in generating size-controlled NPs from biodegradable polymers in the sub-100-nm range. Here, we report the preparation of three sets of poly(lactic-co-glycolic)-b-poly(ethylene-glycol) (PLGA-b-PEG) NPs with number average diameters of 20-, 40-, and 100-nm and narrow size distributions using flash nanoprecipitation. Using NPs labeled with a near-infrared dye, we showed that 20-nm NPs drain rapidly across proximal and distal LNs following subcutaneous inoculation in mice and are retained in LNs more effectively than NPs with a number average diameter of 40-nm. The drainage of 100-nm NPs was negligible. Furthermore, the 20-nm NPs showed the highest degree of penetration around the paracortex region and had enhanced access to dendritic cells in the LNs. Together, these data confirmed that small, size-controlled PLGA-b-PEG NPs at the lower threshold of about 30-nm are most effective for LN trafficking, retention, and APC uptake after s.c. administration. This report could inform the design of LN-targeted NP carrier for the delivery of therapeutic or prophylactic vaccines. Keywords: biodegradable nanoparticle lymph node trafficking vaccine delivery nanoparticle size antigen presenting cells in vivo imaging”

mPEG-PLA from PolySciTech used in development of phospho-sulindac loaded nanoparticles for ocular treatment.

Monday, February 4, 2019, 4:24 PM ET

Delivery of medicines to the ocular region is difficult as most systemic administrations have relatively poor transport to the eyes relative to the rest of the body and any local administration (eye-drops) is washed away quickly by the tear-action of the yes. Recently, researchers at Stony Brook University used mPEG-PLA (AK005) from PolySciTech (www.polyscitech.com) to generate nanoparticles for ocular application. This research holds promise to improve the longevity and efficacy of ocular medications. Read more: Wen, Ziyi, Natsuko Muratomi, Wei Huang, Liqun Huang, Jinfeng Ren, Jennifer Yang, Yogeeta Persaud et al. "The ocular pharmacokinetics and biodistribution of phospho-sulindac (OXT-328) formulated in nanoparticles: Enhanced and targeted tissue drug delivery." International journal of pharmaceutics 557 (2019): 273-279. https://www.sciencedirect.com/science/article/pii/S037851731830975X

“Abstract: We studied the pharmacokinetics, biodistribution and metabolism of phospho-sulindac (PS), a novel agent efficacious in the treatment of dry eye, formulated in nanoparticles (PS-NPs) following its topical administration to the eye of New Zealand White rabbits. The nanoparticles were spherical with effective diameter = 108.9 ± 41.7 nm, zeta potential = −21.70 ± 3.78 mV, drug loading = 7%, and entrapment efficiency = 46.4%. Of the total PS delivered topically to the eye, >95% was retained in the anterior segment, predominantly in the cornea (Cmax = 101.3 μM; Tmax = 1 h; T1/2 = 2.6 h; area AUC0–16h = 164.4 µM·h) and conjunctiva (Cmax = 89.4 μM; Tmax = 0.25 h; T1/2 = 3.1 h; AUC0–16h = 63.5 µM·h), the tissues most affected by dry eye disease. No PS or its metabolites were detected in the systemic circulation. PS was metabolized to PS sulfide and PS sulfone; all three molecules were hydrolyzed to sulindac, which was converted to sulindac sulfide and sulindac sulfone. A solution formulation of PS provided lower PS levels in ocular tissues but higher levels of PS metabolites, compared to PS-NPs. Therefore, NPs represent an effective formulation for the topical ocular administration of PS for anterior segment diseases, such as dry eye disease.”

PLGA from PolySciTech used in development of drug-eluting sinus stent for chronic inflammation treatment

Friday, February 1, 2019, 3:49 PM ET

Chronic inflammation of sinus passageways is a very common disease afflicting ~14-16% of adults in USA. Often bacterial infections in this area are very difficult to treat with systemic antibiotics due to the formation of a bacterial biofilm within the sinus. Severe and chronic sinus infection can require surgical intervention to reopen the passages with placement of a sinus stent. Ideally, the stent provides for a promising platform to provide for drug-delivery to the sinus passageways. Recently, researchers at University of Alabama at Birmingham used a series of PLAs and PLGAs (PolyVivo AP036, AP045, AP059, and AP061) from PolySciTech (www.polyscitech.com) to develop a drug-eluting sinus stent. This research holds promise to provide for improved therapy for this disease which affects many people. Read more: Do‐Yeon Cho, Dong‐Jin Lim, Calvin Mackey, Christopher G. Weeks, Jaime A. Pena Garcia, Daniel Skinner, Shaoyan Zhang, Justin McCormick, Bradford A. Woodworth “In‐vitro evaluation of a ciprofloxacin‐ and ivacaftor‐coated sinus stent against Pseudomonas aeruginosa biofilms” International Forum of Allergy & Rhinology (DOI: 10.1002/alr.22285, 2019) https://onlinelibrary.wiley.com/doi/full/10.1002/alr.22285

“Abstract: Background: We recently developed a novel ciprofloxacin‐coated sinus stent capable of releasing antibiotics over a sustained period of time. Ivacaftor is a cystic fibrosis transmembrane conductance regulator (CFTR) potentiator that has synergistic bactericidal activity with ciprofloxacin and also enhances sinus mucociliary clearance. The objective of this study was to optimize and evaluate the efficacy of a ciprofloxacin‐ and ivacaftor‐releasing biodegradable sinus stent (CISS) in vitro. Methods: A CISS was created by coating ciprofloxacin/ivacaftor‐embedded nanoparticles with an acrylate and ammonium methacrylate copolymer onto a biodegradable poly‐L‐lactic acid stent. In‐vitro evaluation of the CISS included: (1) assessment of drug stability in nanoparticles by zeta potential, and drug‐coating stability within the CISS using scanning electron microscopy (SEM); (2) determination of ciprofloxacin‐ and ivacaftor‐release kinetics; and (3) assessment of anti‒Pseudomonas aeruginosa biofilm formation by calculating relative optical density units (RODUs) compared with control stents at 590‐nm optical density. Results: The presence of drugs and a uniform coating on the stent were confirmed by zeta potential and SEM. Sustained drug release was observed through 21 days without an initial burst release. Anti‐biofilm formation was observed after placing the CISS for 3 days onto a preformed 1‐day P aeruginosa biofilm. The CISS significantly reduced biofilm mass compared with bare stents and controls (RODUs at 590‐nm optical density; CISS, 0.31 ± 0.01; bare stent, 0.78 ± 0.12; control, 1.0 ± 0.00; p = 0.001; n = 3). Conclusion: The CISS maintains a uniform coating and sustained delivery of drugs providing a marked reduction in P aeruginosa biofilm formation. Further studies evaluating the efficacy of CISS in a preclinical model are planned.”

mPEG-PLGA from PolySciTech used in Development of Microwave Manufacturing Technique for Chemotherapeutic-Loaded Nanoparticles

Tuesday, January 22, 2019, 3:59 PM ET

Have you ever looked at a microwave oven and wondered if it could be used to manufacture nanoparticles? Microwave electromagnetic radiation generates heat by vibrating the molecules of whatever is placed within range. In a household, most people use this technology to warm up food, such as breakfast burritos. In a lab, however, this same technology can be applied towards a wide array of applications. Recently, researchers at University of North Carolina at Chapel Hill used PEG-PLGA (AK010, AK037) from PolySciTech (www.polyscitech.com) as part of developing a microwave-based manufacturing technique to develop nanoparticle formulations containing paclitaxel for cancer delivery system. This research holds promise to enable rapid and efficient nanoparticle manufacturing for improved cancer therapy. Read more: Dunn, Stuart S., J. Christopher Luft, and Matthew C. Parrott. "Zapped assembly of polymeric (ZAP) nanoparticles for anti-cancer drug delivery." Nanoscale (2019). https://pubs.rsc.org/en/content/articlehtml/2019/nr/c8nr09944h

“Abstract: The starting hypothesis for this work was that microwave synthesis could enable the rapid assembly of polymers into size-specific nanoparticles (NPs). The Zapped Assembly of Polymeric (ZAP) NPs was initially realized using poly(lactic-co-glycolic acid)-poly(ethylene glycol) (PLGA-PEG) block copolymers and distinct microwave reaction parameters. A library of polymeric NPs was generated with sizes ranging from sub-20 nm to 350 nm and low polydispersity. Select ZAP NPs were synthesized in 30 seconds at different scales and concentrations, up to 200 mg and 100 mg mL−1, without substantial size variation. ZAP NPs with diameters of 25 nm, 50 nm, and 100 nm were loaded with the chemotherapeutic paclitaxel (PXL), demonstrated unique release profiles, and exhibited dose-dependent cytotoxicity similar to Taxol. Incorporation of d-alpha tocopheryl polyethylene glycol succinate (TPGS) and PLGA33k allowed for the production of a sub-40 nm NP with an exceptionally high loading of PXL (12.6 wt%, ca. 7 times the original NP) and a slower release profile. This ZAP NP platform demonstrated scalable, flexible, and tunable synthesis with potential toward clinical scale production of size-specific drug carriers.”

PLGA from PolySciTech used in study on nanoparticle/microparticle interactions with immune cells

Friday, January 18, 2019, 10:20 AM ET

The human immune system does a spectacular job at attacking and destroying anything which is deemed (from a biochemical standpoint) to be ‘non-self’ in nature. In the case of bacterial or viral infection, this is quite a useful and necessary feature which enables humans to survive these infections. In drug delivery applications, however, it presents a problem as particles loaded with medicines intended for delivery of the therapeutic molecule can be attacked by phagocytes (i.e. white blood cells) and destroyed. Recently, researchers at The Indian Institute of Science used PLGA (AP154) from PolySciTech (www.polyscitech.com) to develop nanoparticles and track their cellular interactions. This research holds promise for better understanding of nanoparticle/microparticle circulation and clearance as it applies to drug delivery. Read more: Sharma, Preeti, Devashish Sen, Varsha Neelakantan, Vinidhra Shankar, and Siddharth Jhunjhunwala. "Disparate effects of PEG or albumin based surface modification on uptake of nano-and micro-particles." Biomaterials Science (2019). https://pubs.rsc.org/en/content/articlelanding/2019/bm/c8bm01545g

“Abstract: Surface modification of particulate systems is a commonly employed strategy to alter their interaction with proteins and cells. Past studies on nano-particles have shown that surface functionalization with polyethylene glycol (PEG) or proteins such as albumin increases circulation times by reducing their phagocytic uptake. However, studies on surface functionalized micro-particles have reported contradictory results. Here, we investigate the effects of surface functionalization using polystyrene particles with 4 different diameters ranging from 30 nm-2.6 µm and coating them either with albumin or PEG. Our results show that with increasing particle size, surface functionalization has less to no effect on altering phagocytic uptake. The data also suggests that these differences are observed even with a dense arrangement of molecules on the surface (dense brush conformation for PEG conjugation), appear to be independent of the serum proteins adsorbing on particles surfaces and is independent of the endocytic uptake pathway. These results provide insight into the differences in the ability of surface modified nano- and micro-particles to avoid phagocytic uptake.”

PLGA from PolySciTech used in development of nanoparticle-based antisense oligonucleotide delivery system

Thursday, January 17, 2019, 11:17 AM ET

Antisense oligonucleotides (AS)=O) are synthetic polymers that are short-chain derivatives of DNA or RNA. They can potentially be applied to treating a wide range of diseases by blocking or modifying the synthesis of specific proteins involved in pathological states. However, transporting ASO into the cell where it would work is not easily accomplished. Recently, researchers at University of Copenhagen used PLGA (AP030, AP085, AP054, AP199) from PolySciTech (www.polyscitech.com) as part of designing a nanoparticle system for delivery of antisense oligonucleotides. This research holds promise to enable drug delivery for this class of molecules. Read more: Thanki, Kaushik, Simon Papai, Abhijeet Lokras, Fabrice Rose, Emily Falkenberg, Henrik Franzyk, and Camilla Foged. "Application of a Quality-By-Design Approach to Optimise Lipid-Polymer Hybrid Nanoparticles Loaded with a Splice-Correction Antisense Oligonucleotide: Maximising Loading and Intracellular Delivery." Pharmaceutical Research 36, no. 3 (2019): 37. https://link.springer.com/article/10.1007/s11095-018-2566-3

“Background: Antisense oligonucleotides (ASOs) are promising therapeutics for specific modulation of cellular RNA function. However, ASO efficacy is compromised by inefficient intracellular delivery. Lipid-polymer hybrid nanoparticles (LPNs) are attractive mediators of intracellular ASO delivery due to favorable colloidal stability and sustained release properties. Methods: LPNs composed of cationic lipidoid 5 (L5) and poly(DL-lactic-co-glycolic acid) were studied for delivery of an ASO mediating splice correction of a luciferase gene transcript (Luc-ASO). Specific purposes were: (i) to increase the mechanistic understanding of factors determining the loading of ASO in LPNs, and (ii) to optimise the LPNs and customise them for Luc-ASO delivery in HeLa pLuc/705 cells containing an aberrant luciferase gene by using a quality-by-design approach. Critical formulation variables were linked to critical quality attributes (CQAs) using risk assessment and design of experiments, followed by delineation of an optimal operating space (OOS). Results: A series of CQAs were identified based on the quality target product profile. The L5 content and L5:Luc-ASO ratio (w/w) were determined as critical formulation variables, which were optimised systematically. The optimised Luc-ASO-loaded LPNs, defined from the OOS, displayed high loading and mediated splice correction at well-tolerated, lower doses as compared to those required for reference L5-based lipoplexes, L5-modified stable nucleic acid lipid nanoparticles or LPNs modified with dioleoyltrimethylammonium propane (conventional cationic lipid). Conclusions: The optimal Luc-ASO-loaded LPNs represent a robust formulation that mediates efficient intracellular delivery of Luc-ASO. This opens new avenues for further development of LPNs as a broadly applicable technology platform for delivering nucleic acid cargos intracellularly. Key Words: antisense oligonucleotides in vitro splice correction HeLa pLuc/705 cells lipidoids lipid-polymer hybrid nanoparticles (LPNs) quality-by-design statistical optimization”

PLGA-PEG-PLGA thermogel from PolySciTech used in development of bone-tuberculosis therapy

Monday, January 14, 2019, 4:40 PM ET

Although tuberculosis is commonly associated with the lungs, this bacterial infection can also affect other body parts such as the spinal column (Pott’s disease) or long-bones. This form of the disease is both difficult to diagnose (until it is in late stages) and can lead to severe problems, including neurological problems and paralysis. Typically, transfer of medicinal molecules into bone tissue is poor due to weak vascularization and poor blood flow. In this case, achieving a useful concentration of anti-tuberculosis agent in the bones requires very high dosing of the agent throughout the entire body, which can lead to problematic side effects. Recently, researchers at Central South University (China) used PLGA-PEG-PLGA (AK097) from PolySciTech (www.polyscitech.com) to generate Isoniazid loaded hydrogel. Since the gel can be injected directly to site, this could be used to treat bone tuberculosis without requiring a high dose of the drug across the entire body. This research holds promise to improve treatments for this debilitating disease. Read more: Liu, Peng, Binbin Guo, Shengfeng Wang, Jinsong Ding, and Wenhu Zhou. "A Thermo-Responsive and Self-Healing Liposome-in-Hydrogel System as an Antitubercular Drug Carrier for Localized Bone Tuberculosis Therapy." International Journal of Pharmaceutics (2019). https://www.sciencedirect.com/science/article/pii/S0378517319300201

“Abstract: Isoniazid (INH) is a first-line therapy for bone tuberculosis (TB), but its clinic benefits are limited by severe side-effects after long-time administration. While nano-drug delivery systems present as promising strategies for INH delivery, the therapeutic efficacies are usually suboptimal due to ineffective drug accumulation at diseased sites. Local delivery system can achieve high drug concentration at focus sites with minimal systemic exposure, and herein we aimed to employ this strategy to develop a novel liposome-in-hydrogel system for localized treatment of bone TB. To achieve sustainable drug release, a derivative of INH called DINH was loaded because of its hydrophobicity, as well as its better activity and higher biosafety than INH. The hybrid system was demonstrated for thermo-responsive and self-healing properties via phase transition test and rheological studies, which were particularly useful for intra-articular administration. In vivo microdialysis studies revealed that the system can rapidly release drug into synovial fluid to reach effective inhibitory concentrations after localized injection, followed by a steady-state drug release. The optical image studies were performed to study its long-term behavior in vivo, which suggested a sustained drug release profile for several days. This work provides a promising drug delivery system for bone TB therapy. Keywords: Bone tuberculosis Isoniazid Liposomes Thermo-responsive hydrogel Self-healing”

PLGA from PolySciTech used in development of oral exenatide formulation for diabetes treatment

Tuesday, January 8, 2019, 11:52 AM ET

Diabetes is a highly prevalent disease affecting roughly 30.3 million Americans, leading to nearly 79,000 deaths annually, making it the 7th leading cause of death (ADA, 2015 statistics). Exenatide is a GLP-1 (glucagon-like peptide-1) agonist used to treat type-2 diabetes. Exenatide’s poor bioavailability requires it to be administered as an injection. Since diabetes is a chronic disease, it is preferable for therapy to be easy for patients to self-administer such as an oral formulation (tablet or pill). Recently, researchers at Yantai University (China) used PLGA (Polyvivo AP081) from PolySciTech (www.polyscitech.com) to develop a nanoparticle-exenatide formulation to improve uptake across the intestine for better bioavailability. This research holds promise for improved treatment options for diabetes. Read more: Song, Yina, Yanan Shi, Liping Zhang, Haiyan Hu, Chunyan Zhang, Miaomiao Yin, Liuxiang Chu et al. "Synthesis of CSK-DEX-PLGA nanoparticles for oral delivery of exenatide to improve its mucus penetration and intestinal absorption." Molecular Pharmaceutics (2019). https://pubs.acs.org/doi/abs/10.1021/acs.molpharmaceut.8b00809

“Abstract: Oral absorption of exenatide, a drug for type 2 diabetes treatment, can be improved by using nanoparticles (NPs) for its delivery. To improve the mucus penetration and intestinal absorption of exenatide, we designed a block copolymer, CSKSSDYQC-dextran-poly (lactic-co-glycolic acid) (CSK-DEX-PLGA), and used it for preparation of exenatide-loaded NPs. The functionalized exenatide-loaded NPs composed of CSK-DEX-PLGA were able to target intestinal epithelial cells and reduce the mucus-blocking effect of the intestine. Moreover, the CSK modification of DEX-PLGA was found to significantly promote the absorption efficiency of NPs in the small intestine, based on in vitro ligation of intestinal rings and examination of different intestinal absorption sites. Compared with DEX-PLGA-NPs (DPs), the absorption of CSK-DEX-PLGA-NPs (CDPs) was increased in the villi, allowing the drug to act on goblet-like Caco-2 cells through clathrin-, caveolin- and gap-mediated endocytosis. Furthermore, enhanced transport ability of CDPs was observed in a study on Caco-2/HT-29-MTX co-cultured cells. CDPs exhibited a prolonged hypoglycemic response with a relative bioavailability of 9.2% in diabetic rats after oral administration. In conclusion, CDPs can target small intestinal goblet cells and have a beneficial effect on oral administration of macromolecular peptides as a nanometer-sized carrier.”

These posts are syndicated from John Garner's blog at http://jgakinainc.blogspot.com/ where you can post a question or comment. (Load took 5.3765301704407 seconds)


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