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

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

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

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

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

PLGA/PLA standards now available from Akina, Inc.

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

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

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

Protein Phosphorylation Detection Kit

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

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

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

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

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

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


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


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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

CRS Presentation

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

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

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

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

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

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

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

Memorial Day

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

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

BPCR Free Scientific Networking Conference August 29, 2018

Monday, May 21, 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. This conference focuses on research companies in the biotechnology, pharmaceutical, medical, and broader life-science fields. Speakers include Anton Iliuk (Tymora), Kelvin Okamoto (Gen3Bio), Cedric D’Hue (D’Hue Law), and Raouf Gharbo (Peerbridge Health). Free exhibit-hall booth spaces still available. (BPCRconference.com)

PLGA-amine and PEG-PLGA from PolySciTech used in development of micro-RNA based treatment for glioblastoma

Monday, May 14, 2018, 7:45 PM ET

As DNA is transcribed it proceeds through an RNA (single strand) precursor which is then used to synthesize proteins. One therapeutic strategy is to find RNA counter-sequences which block the transcription for proteins of certain types (i.e. cancer-related factors) as this can reduce the growth and spread of cancer. Recently, researchers at Stanford University used PLGA-NH2 (AI010) and mPEG-PLGA (AK071) from PolySciTech (www.polyscitech) to develop novel brain-cancer therapy. This research holds promise for development of therapeutic strategies against this often fatal form of cancer. Read more: Meenakshi Malhotra, Thillai Veerapazham Sekar, Jeyarama S. Ananta, Rammohan Devulapally, Rayhaneh Afjei, Husam A. Babikir, Ramasamy Paulmurugan, and Tarik F. Massoud “Targeted nanoparticle delivery of therapeutic antisense microRNAs presensitizes glioblastoma cells to lower effective doses of temozolomide in vitro and in a mouse model” Oncotarget. 2018; 9:21478-21494. https://doi.org/10.18632/oncotarget.25135

“ABSTRACT: Temozolomide (TMZ) chemotherapy for glioblastoma (GBM) is generally well tolerated at standard doses but it can cause side effects. GBMs overexpress microRNA-21 and microRNA-10b, two known oncomiRs that promote cancer development, progression and resistance to drug treatment. We hypothesized that systemic injection of antisense microRNAs (antagomiR-21 and antagomiR-10b) encapsulated in cRGD-tagged PEG-PLGA nanoparticles would result in high cellular delivery of intact functional antagomiRs, with consequent efficient therapeutic response and increased sensitivity of GBM cells to lower doses of TMZ. We synthesized both targeted and non-targeted nanoparticles, and characterized them for size, surface charge and encapsulation efficiency of antagomiRs. When using targeted nanoparticles in U87MG and Ln229 GBM cells, we showed higher uptake-associated improvement in sensitivity of these cells to lower concentrations of TMZ in medium. Co-inhibition of microRNA-21 and microRNA-10b reduced the number of viable cells and increased cell cycle arrest at G2/M phase upon TMZ treatment. We found a significant increase in expression of key target genes for microRNA-21 and microRNA-10b upon using targeted versus non-targeted nanoparticles. There was also significant reduction in tumor volume when using TMZ after pre-treatment with loaded nanoparticles in human GBM cell xenografts in mice. In vivo targeted nanoparticles plus different doses of TMZ showed a significant therapeutic response even at the lowest dose of TMZ, indicating that preloading cells with antagomiR-21 and antagomiR-10b increases cellular chemosensitivity towards lower TMZ doses. Future clinical applications of this combination therapy may result in improved GBM response by using lower doses of TMZ and reducing nonspecific treatment side effects.”

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

PLLA from PolySciTech used in development of biodegradable vascular graft

Monday, May 14, 2018, 7:43 PM ET

Heart disease is one of the major causes of mortality worldwide. Biodegradable synthetic grafts can be used to improve healing of blocked or damaged vessels. Recently, researchers from Universitas Airlangga (Indonesia) used PLLA (Cat# AP006) from PolySciTech (www.polyscitech.com) to generate a biodegrdable graft. This research holds promise for providing for treatment of cardiovascular disease. Read more: Iffa A. Fiqrianti, Prihartini Widiyanti, Muhammad A. Manaf, Claudia Y. Savira, Nadia R. Cahyani, and Fitria R. Bella “Poly-L-lactic Acid (PLLA)-Chitosan-Collagen Electrospun Tube for Vascular Graft Application” Journal of Functional Biomaterials 2018, 9, 32; doi:10.3390/jfb9020032 (http://www.mdpi.com/2079-4983/9/2/32)

“Abstract: Poly-L-Lactic acid (PLLA) blended with chitosan and collagen was used to fabricate a conduit for blood vessel engineering through an electrospinning process. Various concentrations of chitosan were used in the blend in order to study its effect on the morphology, chemical bond, tensile strength, burst pressure, hemocompatibility, and cell viability (cytotoxicity) of the tube. In vitro assessments indicated that addition of chitosan-collagen could improve cell viability and hemocompatibility. Best results were demonstrated by the conduit with 10% PLLA, 0.5% chitosan, and 1% collagen. Tensile strength reached 2.13 MPa and burst pressure reached 2593 mmHg, both values that are within the range value of native blood vessel. A hemolysis percentage of 1.04% and a cell viability of 86.2% were obtained, meeting the standards of high hemocompatibility and low cytotoxicity for vascular graft material. The results are promising for further development toward vascular graft application. Keywords: poly L-lactic acid; collagen; chitosan; electrospinning; tube; vascular 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

PEG-PLA from PolySciTech used to develop silver-antibiotic nanoparticle for treatment of MRSA

Monday, May 14, 2018, 3:03 PM ET

For decades, antibiotics have been the ‘go-to’ therapy for a broad range of diseases. In many ways, it has been the development of antibiotics which has allowed society to grow to where it is now. In the absence of these interventions, diseases such as cholera and typhoid would have wiped out large numbers of people. Bacteria, like all living organisms, are adaptive and as time goes by, more and more bacteria are presenting resistance against antibiotics which drastically limits treatment options. Notably, MRSA, remains resistant to most available treatment options and can be deadly. Recently, researchers at Northeastern University used mPEG-PLA (AK021) from PolySciTech (www.polyscitech.com) to develop nanoparticles loaded with silver, gentamicin, and fructose. They found these agents work together to kill MRSA in a synergistic manner. This research holds promise to provide vital treatment options for this nearly incurable disease. Read more: Gelfat, Ilia, Benjamin M. Geilich, and Thomas J. Webster. "Fructose-Enhanced Antimicrobial Activity of Silver Nanoparticle-Embedded Polymersome Nanocarriers." Journal of biomedical nanotechnology 14, no. 3 (2018): 619-626. https://www.ingentaconnect.com/contentone/asp/jbn/2018/00000014/00000003/art00017?crawler=true&mimetype=application/pdf

“Abstract: In recent years, an increasing body of research has indicated that the antimicrobial activity of certain antibiotic drugs can be enhanced by the addition of specific metabolites. This study aimed to incorporate these findings into polymersomes (novel polymer-based nanoscale drug delivery vehicles) which can be loaded with various therapeutic molecules and nanoparticles. Polymersome technology has shown promising results in treating antibiotic-resistant infections by co-encapsulating the antibiotic methicillin with silver nanoparticles. Here, silver nanoparticle-embedded polymersomes (AgPs) were synthesized in a similar fashion with gentamicin replacing methicillin as the antibiotic agent and supplemented with fructose to promote efficacy. Two clinically-isolated strains of methicillin-resistant Staphylococcus aureus (MRSA) (ATCC #43300 and ATCC #25923) were cultured and treated with the new AgP formulations, with the former strain being susceptible to gentamicin and the latter strain being resistant to gentamicin. The treatment of the non-resistant strain yielded promising results with the polymersomes without fructose supplementation inducing a maximal growth rate reduction of up to 40% and an increase in lag time of up to 141% relative to the untreated control. Impressively, the fructose-loaded polymersomes completely eliminated the bacterial growth over the observed time period at the higher doses and outperformed the no-fructose treatment at all concentrations. However, despite significantly reducing bacterial growth, the treatment of the gentamicin-resistant strain did not seem to be enhanced by the addition of fructose. Lastly, the present study demonstrated that the presence of fructose in the polymersomes seemed to slightly ameliorate the cytotoxic effect of the treatment on human dermal fibroblasts (a model mammalian cell). In addition to developing and testing a new polymersome formulation with fructose resulting in increased efficacy, the results of this study also demonstrated the variability inherent to developing novel antimicrobial treatments for different bacterial strains.”

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

Chitosan derivatives from PolySciTech used in the investigation of cuticle interactions to develop advanced materials

Wednesday, May 9, 2018, 3:22 PM ET

There still remains a great deal to learn about how natural materials are structured and how the various components interact. There is a great opportunity for taking lessons how things in nature are constructed and applying that understanding to man-made technologies to improve these designs. A great example is spider silk which, relative to its weight, is one of the strongest substances in nature and a great deal stronger than most man-made materials. Developing this requires an understanding of how the natural material is constructed and how the various components work together. Recently, researchers from the University of Kansas and Kansas State University used low molecular weight and FITC-labelled Chitosan (Kitopure) from PolySciTech (www.polyscitech.com) to investigate the interactions amongst biomacromolecules within insect cuticle. This research holds promise for enabling the generation of advanced biomimetic materials. Read more: Vaclaw, M. Coleman, Patricia A. Sprouse, Neal T. Dittmer, Saba Ghazvini, C. Russell Middaugh, Michael R. Kanost, Stevin H. Gehrke, and Prajnaparamita Dhar. "Self-assembled coacervates of chitosan and an insect cuticle protein containing a Rebers-Riddiford motif." Biomacromolecules (2018). https://pubs.acs.org/doi/abs/10.1021/acs.biomac.7b01637

“The interactions among biomacromolecules within insect cuticle may offer new motifs for biomimetic material design. CPR27 is an abundant protein in the rigid cuticle of the elytron from Tribolium castaneum. CPR27 contains the Rebers–Riddiford (RR) motif, which is hypothesized to bind chitin. In this study, active magnetic microrheology coupled with microscopy and protein particle analysis techniques were used to correlate alterations in the viscosity of chitosan solutions with changes in solution microstructure. Addition of CPR27 to chitosan solutions led to a 3-fold drop in viscosity. This change was accompanied by the presence of micrometer-sized coacervate particles in solution. Coacervate formation had a strong dependence on chitosan concentration. Analysis showed the existence of a critical CPR27 concentration beyond which a significant increase in particle count was observed. These effects were not observed when a non-RR cuticular protein, CP30, was tested, providing evidence of a structure–function relationship related to the RR motif.”

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 the development of Genipin-eluting sutures for tendon repair

Wednesday, May 9, 2018, 3:21 PM ET

Repairing mechanically-stressed tissues, such as tendons, creates a challenging situation in the orthopedic surgical field. Conventionally, sutures work poorly for this application as the strength requirements for holding the tendon in place are very high and the interface between the suture and the tendon creates a weak point which is prone to failure. Genipin is a naturally-derived crosslinking material which can act to potentially reinforce tissues. Recently, researchers from Balgrist University and ETH Zurich (Switzerland) used PLGA (PolyVivo AP081) from PolySciTech (www.polyscitech.com) to develop and test sutures loaded with Genipin for tendon repair. This research holds promise to improve orthopedic surgical outcomes and healing for tendon-repair procedures. Read more: Camenzind, Roland S., Timo O. Tondelli, Tobias Goetschi, Claude Holenstein, and Jess G. Snedeker. "Can Genipin-coated Sutures Deliver a Collagen Crosslinking Agent to Improve Suture Pullout in Degenerated Tendon? An Ex Vivo Animal Study." Clinical Orthopaedics and Related Research 476, no. 5 (2018): 1104-1113. https://journals.lww.com/clinorthop/Fulltext/2018/05000/Can_Genipin_coated_Sutures_Deliver_a_Collagen.34.aspx

“Background The suture-tendon interface is often the weakest link in tendon-to-tendon or tendon-to-bone repair. Genipin is an exogenous collagen crosslink agent derived from the gardenia fruit that can enhance suture force to failure of the tendon-suture interface. Viable methods for intraoperative clinical delivery of genipin could be of clinical utility, but to our knowledge have not yet been extensively studied. Questions/purposes The purposes of this study were (1) to evaluate whether sutures precoated with genipin can augment the suture-tendon interface to improve force to failure, stiffness, and work to failure in healthy and degenerated tendons; and (2) to determine the effect of genipin on the extent and distribution of crosslinking. Methods Single-stitch suture pullout tests were performed ex vivo on 25 bovine superficial digital flexor tendons. To assess effects on native tissue, one group of 12 tendons was cut in proximal and distal halves and randomized to treatment (n = 12) and control groups (n = 12) in a matched-pair design. One simple stitch with a loop with either a normal suture or genipin-coated suture was applied to tendons in both groups. To simulate a degenerative tendon condition, a second group of 13 tendons was cut in proximal and distal halves, injected with 0.2 mL of collagenase D (8 mg/mL) and incubated for 24 hours before suturing with either a genipin-coated suture (n = 13) or their matched controls (n = 13). Sutures from all groups then were loaded to failure on a universal materials testing machine 24 hours after suturing. Suture pullout force, stiffness, and work to failure were calculated from force-displacement data and compared between the groups. Additionally, fluorescence was measured to determine the degree of crosslinking quantitatively and a qualitative analysis of the distribution pattern was performed by microscopy. Results In healthy tendon pairs, the median maximum pullout force was greater with genipin-coated sutures than with control sutures (median, 42 N [range, 24–73 N] versus 29 N [range, 13–48 N]; difference of medians, 13 N; p = 0.003) with corresponding increases in the required work to failure (median, 275 mJ [range, 48–369 mJ] versus 148 mJ [range, 83–369 mJ]; difference of medians, 127 mJ; p = 0.025) but not stiffness (median, 4.1 N/mm [range, 2.3–8.1 N/mm] versus 3.3 N/mm [range, 1.1–9.6 N/mm]; difference of medians, 0.8 N/mm; p = 0.052). In degenerated tendons, median maximum pullout force was greater with genipin-coated sutures than with control sutures (median, 16 N [range, 9-36 N] versus 13 N [range, 5-28 N]; difference of medians, 3 N; p = 0.034) with no differences in work to failure (median, 75 mJ [range, 11–249 mJ] versus 53 mJ [range, 14–143 mJ]; difference of medians, 22 mJ; p = 0.636) or stiffness (median, 1.9 N/mm [range, 0.7–13.4 N/mm] versus 1.6 N/mm [range, 0.5–5.6 N/mm]; difference of medians, 0.3 N/mm; p = 0.285). Fluorescence was higher in tendons treated with genipin-coated sutures compared with the control group, whereas higher fluorescence was observed in the treated healthy compared with the degenerated tendons (difference of means -3.16; standard error 1.08; 95% confidence interval [CI], 0.97–5.34; p = 0.006/healthy genipin: mean 13.04; standard error 0.78; 95% CI, 11.47-14.62; p < 0.001/degenerated genipin: mean 9.88; SD 0.75; 95% CI, 8.34-11.40; p < 0.001). Conclusions Genipin-coated sutures improved force to failure of a simple stitch at the tendon-suture interface in healthy and degenerated tendons in an ex vivo animal model. Fluorescence was higher in tendons treated with genipin-coated sutures compared with the control group. Clinical Relevance A genipin-coated suture represents a potential delivery vehicle for exogenous crosslink agents to augment suture retention properties. In vivo animal studies are the next logical step to assess safety and efficacy of the approach.”

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

Mal-Peg-PLGA from PolySciTech used in development of combination immunotherapy for cancer treatment.

Saturday, May 5, 2018, 10:33 PM ET

One of the more promising methods to treat cancer is the application of immunotherapy. Simply put, this is training the human immune system to attack the cancerous cells as though they were pathogens. There are significant advantages to this technique over other methods that rely on an external agent which kills the cancer cells in that the immune system can attack the cancer throughout the body without damaging normal cells. Recently, researchers at University of North Carolina at Chapel Hill used Mal-PEG-PLGA (PolyVivo AI110) and mPEG-PLGA (AK029) from PolySciTech (www.polyscitech.com) to generate immunotherapy nanoparticles for cancer treatment. This research holds promise to provide for improved therapies against cancer. Read more: Mi, Yu, Christof C. Smith, Feifei Yang, Yanfei Qi, Kyle C. Roche, Jonathan S. Serody, Benjamin G. Vincent, and Andrew Z. Wang. "A Dual Immunotherapy Nanoparticle Improves TCell Activation and Cancer Immunotherapy." Advanced Materials (2018): 1706098. https://onlinelibrary.wiley.com/doi/abs/10.1002/adma.201706098

“Abstract: Combination immunotherapy has recently emerged as a powerful cancer treatment strategy. A promising treatment approach utilizes coadministration of antagonistic antibodies to block checkpoint inhibitor receptors, such as antiprogrammed cell death1 (aPD1), alongside agonistic antibodies to activate costimulatory receptors, such as antitumor necrosis factor receptor superfamily member 4 (aOX40). Optimal Tcell activation is achieved when both immunomodulatory agents simultaneously engage Tcells and promote synergistic proactivation signaling. However, standard administration of these therapeutics as free antibodies results in suboptimal Tcell binding events, with only a subset of the Tcells binding to both aPD1 and aOX40. Here, it is shown that precise spatiotemporal codelivery of aPD1 and aOX40 using nanoparticles (NP) (dual immunotherapy nanoparticles, DINP) results in improved Tcell activation, enhanced therapeutic efficacy, and increased immunological memory. It is demonstrated that DINP elicits higher rates of Tcell activation in vitro than free antibodies. Importantly, it is demonstrated in two tumor models that combination immunotherapy administered in the form of DINP is more effective than the same regimen administered as free antibodies. This work demonstrates a novel strategy to improve combination immunotherapy using nanotechnology.”

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


Thermogelling polymers from Akina, Inc. used in development of controlled medicinal release in the eye

Tuesday, May 1, 2018, 9:15 PM ET

After surgery, several complications can occur as the human body is susceptible to infections, inflammatory response, and swelling. This is especially true in ocular surgery due to the relatively delicate structure of the eye. There are several medications which are effective at preventing infection (antibiotics), inflammation (steroids), and ocular over-pressure (hypotensives). However, each of these medicines is administered repeatedly through eye-drops. Eye-drops typically work poorly as the medicine is flushed away by tears and patients tend to forget to use them. A better solution to ensure appropriate application of medicine is to apply timed-release using a thermogel encapsulating microparticles to ensure each drug gets released at the appropriate times. Recently, researchers at University of Michigan, Johns Hopkins University, and Howard University, used several polymers including PLGA-PEG-PLGA (Polyvivo AK012, AK091), PLA-PEG-PLA (Polyvivo AK100), PLCL-PEG-PLCL (Polyvivo AK108, AK109) as well as PLGA (Polyvivo AP043, AP018, and AP087) from PolySciTech (www.polyscitech.com) to generate microparticle loaded thermogels for controlled delivery of multiple therapeutic agents. This research holds promise to improve the outcomes from ocular surgery by preventing inflammation, infection and swelling. Read more: Mohammadi, Maziar, Kisha Patel, Seyedeh P. Alaie, Ron B. Shmueli, Cagri G. Besirli, Ronald G. Larson, and Jordan J. Green. "Injectable drug depot engineered to release multiple ophthalmic therapeutic agents with precise time profiles for postoperative treatment following ocular surgery." Acta biomaterialia (2018). https://www.sciencedirect.com/science/article/pii/S174270611830240X

“Abstract: A multi-drug delivery platform is developed to address current shortcomings of post-operative ocular drug delivery. The sustained biodegradable drug release system is composed of biodegradable polymeric microparticles (MPs) incorporated into a bulk biodegradable hydrogel made from triblock copolymers with poly(ethylene glycol) (PEG) center blocks and hydrophobic biodegradable polyester blocks such as poly(lactide-co-glycolide) (PLGA), Poly(lactic acid) (PLA), or Poly(lactide-co-caprolactone) (PLCL) blocks. This system is engineered to flow as a liquid solution at room temperature for facile injection into the eye and then quickly gel as it warms to physiological body temperatures (approximately 37 °C). The hydrogel acts as an ocular depot that can release three different drug molecules at programmed rates and times to provide optimal release of each species. In this manuscript, the hydrogel is configured to release a broad-spectrum antibiotic, a potent corticosteroid, and an ocular hypotensive, three ophthalmic therapeutic agents that are essential for post-operative management after ocular surgery, each drug released at its own timescale. The delivery platform is designed to mimic current topical application of postoperative ocular formulations, releasing the antibiotic for up to a week, and the corticosteroid and the ocular hypotensive agents for at least a month. Hydrophobic blocks, such as PLCL, were utilized to prolong the release duration of the biomolecules. This system also enables customization by being able to vary the initial drug loading to linearly tune the drug dose released, while maintaining a constant drug release profile over time. This minimally invasive biodegradable multi-drug delivery system is capable of replacing a complex ocular treatment regimen with a simple injection. Such a depot system has the potential to increase patient medication compliance and reduce both the immediate and late term complications following ophthalmic surgery. Statement of Significance: After ocular surgery, patients routinely receive multiple medications including antibiotics, steroids and ocular hypotensives to ensure optimal surgical outcomes. The current standard of care for postoperative treatment after ocular surgery involves using eye drops daily, which has limited effectiveness mainly due to poor patient adherence. To improve patient experience and outcomes, this article presents the first thermoresponsive hydrogel able to release multiple drug molecules for the application of post-operative treatment following ocular surgery. By varying the parameters such as hydrogel type and polymer hydrophobicity, the drug release profile, duration and dosage can finely be tuned. The approach presented in this article can readily be applied to other applications by simply changing the drug loaded in the drug delivery system.”

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. which focuses on research companies in the biotechnology, pharmaceutical, medical, and broader life-science fields. See more at BPCRconference.com

PLGA-Rhodamine from PolySciTech used in development of nanoparticles to kill bacteria that hide inside of human cells

Tuesday, May 1, 2018, 9:14 PM ET

Klebsiella pneumoniae is a particularly nasty bacterial strain that can survive being swallowed by a cell and is resistant to traditional antibiotics in this state as the cell protects it from these medicines. This bacteria leads to severe lung infections and can be deadly. Recently, researchers at Queen’s University Belfast used PLGA-Rhodamine (PolyVivo AV011) from PolySciTech (www.polyscitech.com) to generate fluorescent-traceable nanoparticles. They tracked the uptake of gentamicin-loaded nanoparticles into cells as a means to treat intra-cellular bacteria. This research holds promise to provide for treatment against this antibiotic-resistant disease. Read more: Jiang, Lai, Michelle K. Greene, Jose Luis Insua, Joana Sa Pessoa, Donna M. Small, Peter Smyth, Aidan McCann et al. "Clearance of intracellular Klebsiella pneumoniae infection using gentamicin-loaded nanoparticles." Journal of Controlled Release (2018). https://www.sciencedirect.com/science/article/pii/S0168365918302244

“Abstract: Klebsiella pneumoniae is a foremost gram-negative pathogen that can induce life-threatening nosocomial pulmonary infections. Although it can be phagocytosed successfully by lung resident macrophages, this pathogen remains viable within vacuolar compartments, resulting in chronic infection and limiting therapeutic treatment with antibiotics. In this study, we aimed to generate and evaluate a cell-penetrant antibiotic poly(lactide-co-glycolide) (PLGA)-based formulation that could successfully treat intracellular K. pneumoniae infection. Screening of formulation conditions allowed the generation of high drug entrapment nanoparticles through a water-in-oil-in-water approach. We demonstrated the therapeutic usefulness of these gentamicin-loaded nanoparticles (GNPs), showing their ability to improve survival and provide extended prophylactic protection towards K. pneumoniae using a Galleria mellonella infection model. We subsequently showed that the GNPs could be phagocytosed by K. pneumoniae infected macrophages, and significantly reduce the viability of the intracellular bacteria without further stimulation of pro-inflammatory or pro-apoptotic effects on the macrophages. Taken together, these results clearly show the potential to use antibiotic loaded NPs to treat intracellular K. pneumoniae infection, reducing bacterial viability without concomitant stimulation of inflammatory or pyroptotic pathways in the treated cells. Keywords: Gentamicin; PLGA; Nanoparticles; Klebsiella pneumoniae; Intracellular infection; Macrophage; Inflammation; Pyroptosis”

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. which focuses on research companies in the biotechnology, pharmaceutical, medical, and broader life-science fields. See more at BPCRconference.com

PLGA from PolySciTech used in development of 3D printed cartilage scaffold for tissue engineering

Tuesday, May 1, 2018, 9:12 PM ET

Tissue engineering is a process by which cells and cell-growth scaffolds are emplaced in a patient where there is damage to the native tissue. Cells must have a surface to grow on so one of the most critical components of any tissue engineering system is a substrate/structure which the cells can grow on and interact with for successfully replacing the original tissue. This is not a trivial process, as most tissues are not uniform and so the interaction between the cells and the substrate is critical. Recently, researchers at the University of Maryland used PLGA (PolyVivo AP024) from PolySciTech (www.polyscitech.com) to generate 3D printed scaffolds and tested these for their cell-interaction capabilities as well as their ability to grow heterogenous tissues. This research holds promise for improving the development of tissue scaffolds to treat a wide range of injuries and disease states. Read more: Guo, Ting, Julia P. Ringel, Casey G. Lim, Laura G. Bracaglia, Maeesha Noshin, Hannah B. Baker, Douglas A. Powell, and John P. Fisher. "3D Extrusion Printing Induces Polymer Molecule Alignment and Cell Organization within Engineered Cartilage." Journal of Biomedical Materials Research Part A (2018). https://onlinelibrary.wiley.com/doi/abs/10.1002/jbm.a.36426

“Abstract: Proper cell–material interactions are critical to remain cell function and thus successful tissue regeneration. Many fabrication processes have been developed to create microenvironments to control cell attachment and organization on a threedimensional (3D) scaffold. However, these approaches often involve heavy engineering and only the surface layer can be patterned. We found that 3D extrusion based printing at high temperature and pressure will result an aligned effect on the polymer molecules, and this molecular arrangement will further induce the cell alignment and different differentiation capacities. In particular, articular cartilage tissue is known to have zonal collagen fiber and cell orientation to support different functions, where collagen fibers and chondrocytes align parallel, randomly, and perpendicular, respectively, to the surface of the joint. Therefore, cell alignment was evaluated in a cartilage model in this study. We used small angle Xray scattering analysis to substantiate the polymer molecule alignment phenomenon. The cellular response was evaluated both in vitro and in vivo. Seeded mesenchymal stem cells (MSCs) showed different morphology and orientation on scaffolds, as a combined result of polymer molecule alignment and printed scaffold patterns. Gene expression results showed improved superficial zonal chondrogenic marker expression in parallelaligned group. The cell alignment was successfully maintained in the animal model after 7 days with distinct MSC morphology between the casted and parallel printed scaffolds. This 3D printing induced polymer and cell alignment will have a significant impact on developing scaffold with controlled cell–material interactions for complex tissue engineering while avoiding complicated surface treatment, and therefore provides new concept for effective tissue repairing in future clinical applications.”

BPCR conference (August 29, 2018 9AM - 4PM: Kurz Purdue Technology Center, West Lafayette, IN) is a free, 1-day scientific networking conference hosted by Akina, Inc. which focuses on research companies in the biotechnology, pharmaceutical, medical, and broader life-science fields. See more at BPCRconference.com

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


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