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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Thermogels from PolySciTech used in research on 3D printing of hydrogel substrates

Friday, January 24, 2020, 10:31 AM ET

Conventional 3D printing relies on heating a plastic above its melting point and then extruding it onto a cooled platform. Conversely, 3D printing with a Thermogel requires placing a cooled Thermogel solution onto a heated plate to form the gel. Recently, researchers at Purdue University and Korea Institute of Industrial Technology used NIPAM-co-MMA (AO023) from PolySciTech (www.polyscitech.com) to create 3-D printable hydrogel matrix. This research holds promise to enable generation of drug delivery systems and tissue scaffolds for biomedical applications in the future. Read more: Cheng, Cih, Yoon Jae Moon, Samuel Haidong Kim, Yong-Cheol Jeong, Jun Young Hwang, George T-C. Chiu, and Bumsoo Han. "Water-matrix interaction at the drop-drop interface during drop-on-demand printing of hydrogels." International Journal of Heat and Mass Transfer 150 (2020): 119327. https://www.sciencedirect.com/science/article/pii/S0017931019342085

“Highlights: Drop-drop interactions during hydrogel printing are explained considering water-matrix interactions within hydrogel drops printed. A similarity mechanism of water-matrix interaction, and associated dimensionless parameter are proposed. The water-matrix interactions at the drop-drop interfance affect the microstructure of hydrogel drops printed. Abstract: Hydrogel-based soft materials have been used in numerous applications in healthcare, food, pharmaceutical, and cosmetic industries. Manufacturing hydrogels whose functional properties and compositions are voxelized at superior spatial resolutions can significantly improve current applications as well as will enable a new generation of soft materials. However, it remains challenging to control the structure and composition of soft materials reliably. In this context, the drop-on-demand (DOD) printing of hydrogels shows excellent potential to address this manufacturing challenge. Despite this potential, a lack of mechanistic understanding of the behavior of printed hydrogel drops makes it challenging to design and optimize DOD printing protocols for a wide variety of hydrogels. In particular, the curing of hydrogel drops, which requires dehydration of printed hydrogel drops, is poorly understood. In this study, thus, a hypothesis was postulated and tested that water-matrix interaction at drop-drop interfaces during curing processes determine the quality of hydrogels printed. Both computational and experimental studies were performed to establish a mechanism of the water-matrix interaction within printed hydrogel drops. The results were further discussed to establish a dimensionless similarity parameter that can characterize water transports during the hydrogel dehydration process. Keywords: Water transport Evaporation Interstitial water Poroelastic material 3D printing”

--> Save-the-date: Akina, Inc's third annual Biotech-Pharma-Cancer-Research (BPCR) conference is August 26 at Kurz Purdue Technology Center (KPTC) (http://bpcrconference.com/).

PLGA from PolySciTech used in development of nanoparticle delivery system for CRISPR–Cas9 plasmid

Friday, January 24, 2020, 10:30 AM ET

Although gene-editing has been promoted as a potential usage of CRISPR technology there remains a lack of method to deliver the components for this to the intraceullular area. Recently, researchers at Virginia Tech used PLGA (AP063) and PLGA-NH2 (AI063) from PolySciTech (www.polyscitech.com) to create plasmid-encapsulated nanoparticles and measured the release from these as part of a DNA delivery system. This research holds promise to unlock the potential of CRISPR by allowing the DNA systems to be uptaken into target cells. Read more: Jo, Ami, Veronica M. Ringel-Scaia, Dylan K. McDaniel, Cassidy A. Thomas, Rui Zhang, Judy S. Riffle, Irving C. Allen, and Richey M. Davis. "Fabrication and characterization of PLGA nanoparticles encapsulating large CRISPR–Cas9 plasmid." Journal of Nanobiotechnology 18, no. 1 (2020): 16. https://link.springer.com/article/10.1186/s12951-019-0564-1

“Background: The clustered regularly interspaced short palindromic repeats (CRISPR) and Cas9 protein system is a revolutionary tool for gene therapy. Despite promising reports of the utility of CRISPR–Cas9 for in vivo gene editing, a principal problem in implementing this new process is delivery of high molecular weight DNA into cells. Results: Using poly(lactic-co-glycolic acid) (PLGA), a nanoparticle carrier was designed to deliver a model CRISPR–Cas9 plasmid into primary bone marrow derived macrophages. The engineered PLGA-based carriers were approximately 160 nm and fluorescently labeled by encapsulation of the fluorophore 6,13-bis(triisopropylsilylethynyl) pentacene (TIPS pentacene). An amine-end capped PLGA encapsulated 1.6 wt% DNA, with an encapsulation efficiency of 80%. Release studies revealed that most of the DNA was released within the first 24 h and corresponded to ~ 2–3 plasmid copies released per nanoparticle. In vitro experiments conducted with murine bone marrow derived macrophages demonstrated that after 24 h of treatment with the PLGA-encapsulated CRISPR plasmids, the majority of cells were positive for TIPS pentacene and the protein Cas9 was detectable within the cells. Conclusions: In this work, plasmids for the CRISPR–Cas9 system were encapsulated in nanoparticles comprised of PLGA and were shown to induce expression of bacterial Cas9 in murine bone marrow derived macrophages in vitro. These results suggest that this nanoparticle-based plasmid delivery method can be effective for future in vivo applications of the CRISPR–Cas9 system. Keywords: Nanoprecipitation Transfection CRISPR–Cas9 PLGA nanoparticles”

--> Save-the-date: Akina, Inc's third annual Biotech-Pharma-Cancer-Research (BPCR) conference is August 26 at Kurz Purdue Technology Center (KPTC) (http://bpcrconference.com/).

PLGA from PolySciTech used in comparative assay of nanoparticle delivery and drug release

Friday, January 24, 2020, 10:16 AM ET

The pathway to generating drug-delivery technologies to treat cancer is not necessarily linear as the process is complex. Notably, the motion of the nanoparticles does not always correlate to successful delivery of drug to the tumor. Recently, researchers at Seoul National University, Catholic University of Korea (Korea), and Purdue University used PLGA (AP020) from PolySciTech (www.polyscitech.com) to create quinic-acid decorated nanoparticles. They found that the motion of the particles did not correlate to efficacy, however, indicating that the release of carfizomib is the limiting step for efficacy. Read more: Jun, Yearin, Jun Xu, Hyungjun Kim, Ji Eun Park, Yoo-Seong Jeong, Jee Sun Min, Naeun Yoon et al. "Carfilzomib delivery by quinic acid-conjugated nanoparticles: Discrepancy between tumoral drug accumulation and anticancer efficacy in a murine 4T1 orthotopic breast cancer model." Journal of Pharmaceutical Sciences (2020). https://www.sciencedirect.com/science/article/pii/S0022354920300137

“Abstract: Despite being a major breakthrough in multiple myeloma therapy, carfilzomib (CFZ, a second-generation proteasome inhibitor drug) has been largely ineffective against solid cancer, possibly due to its pharmacokinetic drawbacks including metabolic instability. Recently, quinic acid (QA, a low-affinity ligand of selectins upregulated in peritumoral vasculature) was successfully utilized as a surface modifier for nanoparticles containing paclitaxel. Here, we designed QA-conjugated nanoparticles containing CFZ (CFZ@QANP; the surface of poly(lactic-co-glycolic acid) (PLGA) nanoparticles modified by conjugation with a QA derivative). Compared to the clinically used cyclodextrin-based formulation (CFZ-CD), CFZ@QANP enhanced the metabolic stability and in vivo exposure of CFZ in mice. CFZ@QANP however showed little improvement in suppressing tumor growth over CFZ-CD against the murine 4T1 orthotopic breast cancer model. CFZ@QANP yielded no enhancement in proteasomal inhibition in excised tumors despite having a higher level of remaining CFZ than CFZ-CD. These results likely arise from delayed, incomplete CFZ release from CFZ@QANP as observed using biorelevant media in vitro. These results suggest that the applicability of QANP may not be predicted by physicochemical parameters commonly used for formulation design. Our current results highlight the importance of considering drug release kinetics in designing effective CFZ formulations for solid cancer therapy. Keywords: Proteasome inhibitor carfilzomib nanoparticle quinic acid”

--> Save-the-date: Akina, Inc's third annual Biotech-Pharma-Cancer-Research (BPCR) conference is August 26 at Kurz Purdue Technology Center (KPTC) (http://bpcrconference.com/).

PLA from PolySciTech used in development of Rivastigmine-based therapy for Alzheimer’s disease

Tuesday, January 21, 2020, 4:33 PM ET

Alzheimer’s disease is a progressive neurodegenerative disease which has few treatment options. Recently, Researchers at North Dakota State University used PLA (AP047) from PolySciTech (www.polyscitech.com) as part of developing a depot formulation for treatment of alzeheimers disease. This research holds promise to provide enhanced therapies against alzeheimer’s disease. Read more: Lipp, Lindsey, Divya Sharma, Amrita Banerjee, and Jagdish Singh. "In Vitro and in Vivo Optimization of Phase Sensitive Smart Polymer for Controlled Delivery of Rivastigmine for Treatment of Alzheimer’s Disease." Pharmaceutical Research 37, no. 3 (2020): 34. https://link.springer.com/article/10.1007/s11095-020-2757-6

“Abstract: Purpose: Alzheimer’s disease is a neurodegenerative disorder, and most common form of dementia afflicting over 35 million people worldwide. Rivastigmine is a widely used therapeutic for ameliorating clinical manifestations of Alzheimer’s disease. However, current treatments require frequent dosing either orally or via transdermal patch that lead to compliance issues and administration errors risking serious adverse effects. Our objective was to develop a smart polymer based delivery system for controlled release of rivastigmine over an extended period following a single subcutaneous injection. Methods: Rivastigmine release was optimized by tailoring critical factors including polymer concentration, polymer composition, drug concentration, solvent composition, and drug hydrophobicity (rivastigmine tartrate vs base). Optimized in vitro formulation was evaluated in vivo for safety and efficacy. Results: Formulation prepared using PLGA (50:50) at 5% w/v in 95:5 benzyl benzoate: benzoic acid demonstrated desirable controlled drug release characteristics in vitro. The formulation demonstrated sustained release of rivastigmine tartrate for 7 days in vivo with promising biocompatibility and acetylcholinesterase inhibition efficacy for 14 days. Conclusion: The results exemplify an easily injectable controlled release formulation of rivastigmine prepared using phase-sensitive smart polymer. The optimized formulation significantly increases the dosing interval, and can potentially improve patient compliance as well as quality of life of patients living with Alzheimer’s disease. Key Words: alzheimer’s disease controlled release phase sensitive rivastigmine smart polymers”

--> Save-the-date: Akina, Inc's third annual Biotech-Pharma-Cancer-Research (BPCR) conference is August 26 at Kurz Purdue Technology Center (KPTC) (http://bpcrconference.com/).

PLGA-PEG-Mal from PolySciTech used in development of breast-cancer targeting nanoparticle system.

Tuesday, January 21, 2020, 4:33 PM ET

Despite advances in therapies certain types of breast cancers known as triple-negative breast cancers remain difficult to treat due to their invasive nature and lack of specific target. Recently, researchers at University of Maryland, Translational Genomics Research Institute, and Mayo Clinic Arizona used PLGA-PEG-maleimide (AI053), mPEG-PLGA (AK010), and PLGA-rhodamine (AV011) from PolySciTech (www.polyscitech.com) to develop a series of targeted nanoparticles and tested these for efficacy against triple-negative breast cancer. This research holds promise to improve therapies against breast and other cancers. Read more: Dancy, Jimena G., Aniket S. Wadajkar, Nina P. Connolly, Rebeca Galisteo, Heather M. Ames, Sen Peng, Nhan L. Tran et al. "Decreased nonspecific adhesivity, receptor-targeted therapeutic nanoparticles for primary and metastatic breast cancer." Science Advances 6, no. 3 (2020): eaax3931. https://advances.sciencemag.org/content/advances/6/3/eaax3931.full.pdf

“Abstract: Development of effective tumor cell–targeted nanodrug formulations has been quite challenging, as many nanocarriers and targeting moieties exhibit nonspecific binding to cellular, extracellular, and intravascular components. We have developed a therapeutic nanoparticle formulation approach that balances cell surface receptor-specific binding affinity while maintaining minimal interactions with blood and tumor tissue components (termed “DART” nanoparticles), thereby improving blood circulation time, biodistribution, and tumor cell–specific uptake. Here, we report that paclitaxel (PTX)–DART nanoparticles directed to the cell surface receptor fibroblast growth factor–inducible 14 (Fn14) outperformed both the corresponding PTX-loaded, nontargeted nanoparticles and Abraxane, an FDA-approved PTX nanoformulation, in both a primary triple-negative breast cancer (TNBC) model and an intracranial model reflecting TNBC growth following metastatic dissemination to the brain. These results provide new insights into methods for effective development of therapeutic nanoparticles as well as support the continued development of the DART platform for primary and metastatic tumors.”

--> Save-the-date: Akina, Inc's third annual Biotech-Pharma-Cancer-Research (BPCR) conference is August 26 at Kurz Purdue Technology Center (KPTC) (http://bpcrconference.com/).

PLGA from PolySciTech used in development of 3D-printable Bioink for biomedical applications

Tuesday, January 21, 2020, 4:32 PM ET

3D Printing is a powerful technique which enables generation of unique structures that can be widely applied to biomedical applications. Recently, researchers from University of Prince Edward Island (Canada) used PLGAs (AP149, AP136, AP020, and AP021) from PolySciTech (www.polyscitech.com) to develop a series of 3D printable constructs. This research holds promise to provide improved drug-eluting implants and scaffolds. Read more: Naseri, Emad, Haley Butler, Wyatt MacNevin, Marya Ahmed, and Ali Ahmadi. "Low-temperature solvent-based 3D printing of PLGA: a parametric printability study." Drug Development and Industrial Pharmacy just-accepted (2020): 1-13. https://www.tandfonline.com/doi/abs/10.1080/03639045.2019.1711389

“Abstract: In this paper, a novel low-temperature 3D printing technique is introduced and characterized through a parametric printability study to fabricate poly-lactic-co-glycolic acid (PLGA) constructs using methyl ethyl ketone (MEK) as a solvent. The effects of varying concentrations of PLGA in MEK solvent, lactic to glycolic ratio of PLGA, the molecular weight of PLGA, and the scaling of PLGA constructs on the printability are investigated. PLGA concentrations of higher than 80% w/v, lactic to glycolic ratio more than 75%, molecular weight more than 100 kDa, and printing through nozzles smaller than 0.96 mm internal diameter are recommended for 3D printing of PLGA constructs with high shape fidelity. Ultimately, a vacuum drying solvent removal process is implemented, and Proton Nuclear Magnetic Resonance (1H-NMR) spectroscopy is used to confirm complete removal of the solvent from PLGA constructs. The results of this study can be used for the development of drug-eluting implants. Keywords: 3D printing, PLGA, Printability, Drug Eluting Implants, Bioabsorbable Scaffolds”

--> Save-the-date: Akina, Inc's third annual Biotech-Pharma-Cancer-Research (BPCR) conference is August 26 at Kurz Purdue Technology Center (KPTC) (http://bpcrconference.com/).

Polymer University 107: Unboxing AK149

Friday, January 17, 2020, 1:44 PM ET

Tech video featuring methoxy poly(ethylene glycol)-b-poly(DL)lactide copolymer and its use in formulating nanoparticles for poorly soluble drug delivery. Humorously presented in the format of a classic 'unboxing video.'

PLCL from PolySciTech used in development of vascular grafts.

Tuesday, January 14, 2020, 11:04 AM ET

All parts of the body require continuous exposure to oxygenated blood to stay alive. Damage to vascular systems can occur from a variety of causes (cholesterol blockage, wall-thinning/rupture, trauma, etc.) and in these situations the blood vessels may need surgically repaired to maintain blood flow to critical regions. Recently, researchers at Nanyang Technological University (Singapore) and Technion–Israel Institute of Technology (Israel) used PLCL (AP124, AP145) from PolySciTech (www.polyscitech.com) to create prototype vascular grafts. This research holds promise to improve vascular grafting as a treatment option for damaged blood vessels. Read more: Behr, Jean‐Marc, Scott Alexander Irvine, Chaw‐Su Thwin, Ankur Harish Shah, Min‐Chul Kraun Bae, Eyal Zussman, and Subbu Venkatraman. "Matching Static and Dynamic Compliance of Small‐Diameter Arteries, with Poly (lactide‐co‐caprolactone) Copolymers: In Vitro and In Vivo Studies." Macromolecular Bioscience (2020): 1900234. https://onlinelibrary.wiley.com/doi/abs/10.1002/mabi.201900234

“Abstract: Mechanical mismatch between vascular grafts and blood vessels is a major cause of smaller diameter vascular graft failure. To minimize this mismatch, several poly‐l‐lactide‐co‐ε‐caprolactone (PLC) copolymers are evaluated as candidate materials to fabricate a small diameter graft. Using these materials, tubular prostheses of 4 mm inner diameter are fabricated by dip‐coating. In vitro static and dynamic compliance tests are conducted, using custom‐built apparatus featuring a closed flow system with water at 37 °C. Grafts of PLC monomer ratio of 50:50 are the most compliant (1.56% ± 0.31∙mm Hg−2), close to that of porcine aortic branch arteries (1.56% ± 0.43∙mm Hg−2), but underwent high continuous dilatation (87 µm min−1). Better matching is achieved by optimizing the thickness of a tubular conduit made from 70:30 PLC grafts. In vivo implantation and function of a PLC 70:30 conduit of 150 µm wall‐thickness (WT) are tested as a rabbit aorta bypass. An implanted 150 µm WT PLC 70:30 prosthesis is observed over 3 h. The recorded angiogram shows continuous blood flow, no aneurysmal dilatation, leaks, or acute thrombosis during the in vivo test, indicating the potential for clinical applications.”

--> Save-the-date: Akina, Inc's third annual Biotech-Pharma-Cancer-Research (BPCR) conference is August 26 at Kurz Purdue Technology Center (KPTC) (http://bpcrconference.com/).

PLLA from PolySciTech used in research on controlling immune-response to implant surfaces

Tuesday, January 14, 2020, 11:03 AM ET

In many ways, the human immune system can be considered to be similar to a viscous dog on a chain. It will attack anything that gets within reach that it does not recognize as part of its owner or self. This is great when it comes to bacterial and viral infections which legitimately need to be attacked to prevent infection. This is not great when it comes to medical implants and other materials which may evoke an inflammatory response. Recently, researchers at The Heart Research Institute (Sydney, Australia) University of Sydney (Australia), Shanghai Tongji University, and Shanghai Jiaotong University School of Medicine (China) used PLLA (AP006) from PolySciTech (www.polyscitech.com) to create electrospun meshes of this polymer. They treated these meshes with M-CSF and tested the ability of this treatment to reduce the inflammation response. This research holds promise to improve the functionality of implant materials by reducing the body’s immune response against it. Read more: Yang, Nianji, Richard P. Tan, Alex HP Chan, Bob SL Lee, Miguel Santos, Juichien Hung, Yun Liao et al. "Immobilised Macrophage Colony-Stimulating Factor (M-CSF) regulates the foreign body response to implanted materials." ACS Biomaterials Science & Engineering (2020). https://pubs.acs.org/doi/abs/10.1021/acsbiomaterials.9b01887

“Abstract: The functionality and durability of implanted biomaterials are often compromised by an exaggerated foreign body reaction (FBR). M1/M2 polarization of macrophages is a critical regulator of scaffold-induced FBR. Macrophage colony-stimulating factor (M-CSF), a hematopoietic growth factor, induces macrophages into an M2-like polarized state, leading to immunoregulation and promoting tissue repair. In the present study, we explored the immunomodulatory effects of surface bound M-CSF on poly-l-lactic acid (PLLA)-induced FBR. M-CSF was immobilized on the surface of PLLA via plasma immersion ion implantation (PIII). M-CSF functionalized PLLA, PLLA-only, and PLLA+PIII were assessed in an IL-1β luciferase reporter mouse to detect real-time levels of IL-1β expression, reflecting acute inflammation in vivo. Additionally, these different treated scaffolds were implanted subcutaneously into wild-type mice to explore the effect of M-CSF in polarization of M2-like macrophages (CD68+/CD206+), related cytokines (pro-inflammatory: IL-1β, TNF and MCP-1; anti-inflammatory: IL-10 and TGF-β), and angiogenesis (CD31) by immunofluorescent staining. Our data demonstrated that IL-1β activity in M-CSF functionalized scaffolds was ∼50% reduced compared to PLLA-only at day 1 (p < 0.01) and day 2 (p < 0.05) post-implantation. There were >2.6-fold more CD206+ macrophages in M-CSF functionalized PLLA compared to PLLA-only at day 7 (p < 0.001), along with higher levels of IL-10 at both day 7 (p < 0.05) and day 14 (p < 0.01), and TGF-β at day 3 (p < 0.05), day 7 (p < 0.05), and day 14 (p < 0.001). Lower levels of pro-inflammatory cytokines were also detected in M-CSF functionalized PLLA in the early phase of the immune response compared to PLLA-only: a ∼58% decrease at day 3 in IL-1β; a ∼91% decrease at day 3 and a ∼66% decrease at day 7 in TNF; and a ∼60% decrease at day 7 in MCP-1. Moreover, enhanced angiogenesis inside and on/near the scaffold was observed in M-CSF functionalized PLLA compared to PLLA-only at day 3 (p < 0.05) and day 7 (p < 0.05), respectively. Overall, M-CSF functionalized PLLA enhanced CD206+ macrophage polarization and angiogenesis, consistent with lower levels of pro-inflammatory cytokines and higher levels of anti-inflammatory cytokines in early stages of the host response, indicating potential immunoregulatory functions on the local environment.”

--> Save-the-date: Akina, Inc's third annual Biotech-Pharma-Cancer-Research (BPCR) conference is August 26 at Kurz Purdue Technology Center (KPTC) (http://bpcrconference.com/).

PLGA from PolySciTech used in development of Quinacrine-loaded PLGA nanoparticles for treatment of lung-cancer

Tuesday, January 14, 2020, 11:02 AM ET

A relatively untapped source of novel therapeutic compounds is the reapplication of existing drugs for new purposes. Doing this requires novel applications and delivery systems. Quinacrine, traditionally an antimalarial drug, has shown promise as an anticancer agent under the right conditions. Recently, researchers at Harvard University, Keck Graduate Institute, St. John’s University, and University of La Verne used PLGA (AP082) from PolySciTech (www.polyscitech.com) to create Quinacrine-loaded PLGA nanoparticles for treatment of lung-cancer. This research holds promise to provide for improved therapies against lung-cancer. Read more: Vaidya, Bhuvaneshwar, Nishant S. Kulkarni, Snehal K. Shukla, Vineela Parvathaneni, Gautam Chauhan, Jenna K. Damon, Apoorva Sarode et al. "Development of Inhalable Quinacrine Loaded Bovine Serum Albumin Modified Cationic Nanoparticles: Repurposing Quinacrine for Lung Cancer Therapeutics." International Journal of Pharmaceutics (2020): 118995. https://www.sciencedirect.com/science/article/pii/S0378517319310567

“Abstract: Drug repurposing is on the rise as an atypical strategy for discovery of new molecules, involving use of pre-existing molecules for a different therapeutic application than the approved indication. Using this strategy, the current study aims to leverage effects of quinacrine (QA), a well-known anti-malarial drug, for treatment of non-small cell lung cancer (NSCLC). For respiratory diseases, designing a QA loaded inhalable delivery system has multiple advantages over invasive delivery. QA-loaded nanoparticles (NPs) were thus prepared using polyethyleneimine (PEI) as a cationic stabilizer. While the use of PEI provided cationic charge on the particles, it also mediated a burst release of QA and demonstrated potential particle toxicity. These concerns were circumvented by coating nanoparticles with bovine serum albumin (BSA), which retained the cationic charge, reduced NP toxicity and modulated QA release. Prepared nanoparticles were characterized for physicochemical properties along with their aerosolization potential. Therapeutic efficacy of the formulations was tested in different NSCLC cells. Mechanism of higher anti-proliferation was evaluated by studying cell cycle profile, apoptosis and molecular markers involved in the progression of lung cancer. BSA coated QA nanoparticles demonstrated good aerosolization potential with a mass median aerodynamic diameter of significantly less than 5µm. Nanoparticles also demonstrated improved therapeutic efficacy against NSCLC cells in terms of low IC50 values, cell cycle arrest at G2/M phase and autophagy inhibition leading to increased apoptosis. BSA coated QA NPs also demonstrated enhanced therapeutic efficacy in a 3D cell culture model. The present study thus lays solid groundwork for pre-clinical and eventual clinical studies as a standalone therapy and in combination with existing chemotherapeutics.”

--> Save-the-date: Akina, Inc's third annual Biotech-Pharma-Cancer-Research (BPCR) conference is August 26 at Kurz Purdue Technology Center (KPTC) (http://bpcrconference.com/).

PLGA from PolySciTech used in development of Intra-ductal delivery system for Breast Cancer Therapy

Wednesday, January 8, 2020, 2:22 PM ET

Treating cancer by chemotherapy and other therapeutic means requires maintaining a very high drug concentration at the tumor site and minimizing the drug concentration in other parts of the body where it can cause side effects. For breast cancers, the mammary ducts provide regions where doses could potentially be administered however keeping the dose in that location without flowing to other parts of the body remains a challenge. Recently, researchers at South Dakota State University used PLGA (AP211, AP252, AP062) from PolySciTech (www.polyscitech.com) to develop microparticle and in-situ gel formulations for nanoparticle delivery into the mammary ducts. This research holds promise to improve breast cancer therapies in the future. Read more: Joseph, Mibin Kuruvilla, Md Saiful Islam, Joshua Reineke, Michael Hildreth, Tofuko Woyengo, Angela Pillatzki, Aravind Baride, and Omathanu Perumal. "Intraductal Drug Delivery to the Breast: Effect of Particle size and Formulation on Breast Duct and Lymph Node Retention." Molecular Pharmaceutics (2019). https://pubs.acs.org/doi/abs/10.1021/acs.molpharmaceut.9b00879

“Abstract: Drug delivery by direct intraductal administration can achieve high local drug concentration in the breast and minimize systemic levels. However, the clinical application of this approach for breast cancer treatment is limited by the rapid clearance of the drug from the ducts. With the goal of developing strategies to prolong drug retention in the breast, this study was focused on understanding the influence of particle size and formulation on breast duct and lymph node retention. Fluorescent labeled polystyrene (PS) particles ranging in size from 100-1000 nm were used to study the influence of particle size. Polylactic acid-co-glycolic acid (PLGA) was used to develop and test formulations for intraductal delivery. Cy5.5, a near IR dye was encapsulated in PLGA microparticles, nanoparticles and in-situ gel to study the biodistribution in rats using an in-vivo imager. PS microparticles (1 µm) showed longer retention in the duct compared to 100 and 500 nm nanoparticles. The ductal retention half-life was five-fold higher for PS microparticles compared to the nanoparticles. On the other hand, the free dye was cleared from the breast within 6 hours. PLGA nanoparticles sustained the release of Cy 5.5 for >4 days. Microparticles and gel showed a much slower release than nanoparticles. PLGA in-situ gel and microparticles were retained in the breast for up to 4 days, while the nanoparticles were retained in the breast for 2 days. PLGA nanoparticles and microparticles drained to the axillary lymph node and were retained for up to 24 hours and 48 hours respectively, while the in-situ gel and free dye did not show any detectable fluorescence in the lymph nodes. Taken together, the results demonstrate the feasibility of prolonged retention in the breast duct and lymph node by optimal formulation design. The findings can serve as a framework to design formulations for localized treatment of breast cancer.”

--> Save-the-date: Akina, Inc's third annual Biotech-Pharma-Cancer-Research (BPCR) conference is August 26 at Kurz Purdue Technology Center (KPTC) (http://bpcrconference.com/).

mPEG-PLA and mPEG-PCL from PolyScitech used in research on micelle stability in biological fluids

Thursday, January 2, 2020, 3:52 PM ET

Polymer micelles for drug delivery are typically comprised of hydrophobic (typically a polyester) and hydrophilic (typically PEG) arms on a block copolymer. Based on the polymer as well as the formulation approaches the resultant micelle can have a wide range of properties including size, zeta potential, etc. Although often tested in either plain water or saline, it is important to understand the behavior of these formulations in biological fluids where they will ultimately need to be in order to be used in drug-delivery applications. Recently, researchers at University of Illinois at Chicago used mPEG-PCL (Polyvivo AK073), and mPEG-PLA (AK009, AK054) from PolySciTech (www.polyscitech.com) to test polymer micelle stability in a series of biological fluids. This research holds promise for improved development of micelles for drug-delivery applications. Read more: Langridge, Timothy D., and Richard A. Gemeinhart. "Toward understanding polymer micelle stability: Density ultracentrifugation offers insight into polymer micelle stability in human fluids." Journal of Controlled Release (2019). https://www.sciencedirect.com/science/article/pii/S0168365919307576

“Abstract: Micelles, as a class of drug delivery systems, are underrepresented among United States Food and Drug Administration approved drugs. A lack of clinical translation of these systems may be due to, in part, to a lack of understanding of micelle interactions with biologic fluids following injection. Despite the limited clinical translation, micelles remain an active area of research focus and pre-clinical development. The goal of the present study was to examine the stability of amphiphilic block copolymer micelles in biologic fluids to identify the properties and components of biologic fluids that influence micelle stability. Micelle stability, measured via Förster resonance energy transfer-based fluorescent spectrometry, was complemented with density ultracentrifugation to reveal the colocalized, or dissociated, state of the dye cargo after exposure to human biologic fluids. Polymeric micelles composed of poly(ethylene glycol-block-caprolactone) (mPEG-CL) and poly(ethylene glycol-block-lactide) (mPEG-LA) were unstable in fetal bovine serum, human serum and synovial fluid, with varying levels of instability observed in ascites and pleural fluid. All polymeric micelles exhibited stability in cerebrospinal fluid, highlighting the potential for local cerebro-spinal administration of micelles. Interestingly, mPEG2.2k-CL3.1k and mPEG2k-LA2.7k micelles favored dissolution whereas mPEG5.4k-LA28.5k micelles favored stability. Taken together, our data offers both quantitative and qualitative evidence for micelle stability within human biologic fluids and offers evidence of polymer micelle instability in biologic fluids that is not explained by either total protein content or total unsaturated lipid content. The results help to identify potential sites for local delivery where stability is maintained. Highlights: Human serum is one of the most destabilizing biologic fluids for polymer micelles. Polymer micelles appear stable in human cerebrospinal fluid. Biologic fluid total protein & lipid do not correlate with micelle instability. Typical micelle parameters do not correlate with destabilization in biologic fluids. Gradient ultracentrifugation complements other micelle characterization methods. Keywords: Micelle Stability Gradient ultracentrifugation Critical micelle concentration Human fluid”

--> Save-the-date: Akina, Inc's third annual Biotech-Pharma-Cancer-Research (BPCR) conference is August 26 at Kurz Purdue Technology Center (KPTC) (http://bpcrconference.com/)

PLGA from PolySciTech used in development of antibiotic-releasing films from sinus stent

Thursday, January 2, 2020, 3:51 PM ET

Chronic sinus infection can occur from antibiotic-resistant forms of pseudomonas bacteria. One means to hold the sinus open is to place a stent however further healing can be accomplished by having a drug-eluting layer on the stent release medicines into the surrounding tissue. Recently, researchers at The University of Alabama at Birmingham utilized PLGA from PolySciTech (www.polyscitech.com) as part of their development of a drug-eluting sinus stent. This research holds promise to improve therapies against antibiotic-resistant strains of bacteria that can lead to sinus issues. Read more: Lim, Dong‐Jin, Justin McCormick, Daniel Skinner, Shaoyan Zhang, Jeffrey B. Elder, John G. McLemore, Mark Allen et al. "Controlled delivery of ciprofloxacin and ivacaftor via sinus stent in a preclinical model of Pseudomonas sinusitis." In International Forum of Allergy & Rhinology. John Wiley & Sons, Ltd, 2019. https://onlinelibrary.wiley.com/doi/abs/10.1002/alr.22514

“Abstract: Background: Pseudomonas aeruginosa is common in chronic rhinosinusitus (CRS) and frequently resistant to antibiotic treatment. We recently described the ciprofloxacin and ivacaftor‒releasing biodegradable sinus stent (CISS)―a drug‐delivery system that administers ciprofloxacin and the mucociliary activator (ivacaftor) at high local concentrations with prolonged mucosal contact time and sustained delivery. The objective of this study is to evaluate the efficacy of the CISS in a rabbit model of P aeruginosa (PAO1 strain) sinusitis. Methods: Ciprofloxacin/ivacaftor (double layer) was coated on biodegradable poly‐D/L‐lactic acid (PLLA). A total of 10 sinus stents (5 bare PLLA stent controls, 5 CISSs) were placed unilaterally in rabbit maxillary sinuses via dorsal sinusotomy after inducing infection for 1 week with PAO1. Animals were assessed 3 weeks after stent insertion with sinus culture, nasal endoscopy, computed tomography scan, histopathology, and in‐vivo sinus potential difference (SPD) assay. Results: Rabbits treated with CISS had significant reductions in computed tomography (∆ Kerschner scale: control, 0.55 ± 0.92; CISS, −5.92 ± 1.69; p = 0.024) and endoscopy (control, 4.0 ± 0.0; CISS, 1.875 ± 0.74; p = 0.003) scores. A 2‐log reduction of PAO1 was observed (control, −2.14 ± 0.77; CISS, 1.84 ± 1.52; p = 0.047). SPD revealed significantly increased Cl− transport in the CISS group compared with the control group (Cl−‐free + forskolin ΔPD: control, −4.23 ± 1.04 mV; CISS, −18.36 ± 6.31 mV; p = 0.026). Finally, marked improvements were noted in the histology of the mucosa and submucosa in treated animals. Conclusion: The CISS had robust clinical efficacy in treating P aeruginosa rabbit sinusitis. The innovative design of double‐layered drug coating on the surface of the biodegradable stent may provide therapeutic advantages over current treatment strategies for P aeruginosa sinusitis.”

--> Save-the-date: Akina, Inc's third annual Biotech-Pharma-Cancer-Research (BPCR) conference is August 26 at Kurz Purdue Technology Center (KPTC) (http://bpcrconference.com/).

PLGA from PolySciTech used in development of novel tissue adhesive formulation

Thursday, January 2, 2020, 3:50 PM ET

During surgery and for healing of traumatic injuries it is often necessary to use bioadhesives to close wounds and hold tissues together. Such adhesives must have good adhesion to wet tissue (underlying skin, muscle, fat, etc.) as well as good biocompatibility/biodegradation to allow for subsequent healing of the joined tissues. Recently, researchers at The Pennsylvania State University, Harvard Medical School, (USA) Harbin Engineering University, Chengdu University, Southern Medical University, and Jilin Medical University (China) used PLGA (PolyVivo AP154) from PolySciTech (www.polyscitech.com) as a control article in their development of a citrate-based adhesive. This research holds promise to lead to improvements in tissue adhesives for surgical and regenerative medicine applications. Read more: Lu, Xili, Sanjun Shi, Hanmei Li, Ethan Gerhard, Zhihui Lu, Xinyu Tan, Wenliang Li et al. "Magnesium oxide-crosslinked low-swelling citrate-based mussel-inspired tissue adhesives." Biomaterials (2019): 119719. https://www.sciencedirect.com/science/article/pii/S0142961219308373

“Abstract: Tissue adhesives are commonly used in surgeries and regenerative engineering for the repair and regeneration of topical and internal wounds on tissues and organs such as skin, heart, blood vessels, and bone. However, achieving rapid crosslinking, strong wet adhesion and cohesion strengths, and minimal cytotoxicity remains a critical roadblock for clinical translation. Herein, in contrast to harsh and cytotoxic oxidants, magnesium oxide (MgO) particles were found to facilitate rapid crosslinking for injectable citrate-based mussel-inspired tissue bioadhesives synthesized by reacting citric acid, PEG-PPG-PEG diol and dopamine (iC-EPE). Our results confirmed the role of MgO particles as both crosslinkers and composite fillers to concurrently enhance bioadhesive cohesion and adhesion. iC-EPE crosslinked by MgO with/without sodium periodate (PI) exhibit enhanced mechanical strengths (1.0 Mpa < tensile strength ≤ 4.5 MPa) compared to that of iC-EPE crosslinked only by PI (~0.75 MPa), high adhesion strength (up to 125 kPa, 8 fold that of fibrin glue (~15 kPa)), tunable degradability (full degradation from <1 to="" week=""> 1 month), excellent in vitro and in vivo biocompatibility, encouraging anti-bacterial performance, and favorable wound closure efficacy. Thus, MgO crosslinked bioadhesives possess great potential for a wide range of applications in surgery and regenerative engineering. Keywords: Magnesium oxide (MgO), Mussel-inspired adhesion, Citrate, Tissue adhesives, Wound closure”

--> Save-the-date: Akina, Inc's third annual Biotech-Pharma-Cancer-Research (BPCR) conference is August 26 at Kurz Purdue Technology Center (KPTC) (http://bpcrconference.com/).

mPEG-PLA from PolySciTech used in the development of a Vessel-Perfusion system to better track nanoparticle motility and uptake

Monday, December 23, 2019, 3:20 PM ET

A classic problem with medicine is that the administered dose has poor uptake or targeting which reduces the efficacy of the drug. Having a better understanding for how drug loaded in nanoparticles move and are uptaken in blood vessels will enable the development of improved targeted therapies. Recently, researchers at Yale University used mPEG-PLA (Polyvivo AK054) from PolySciTech (www.polyscitech.com) as part of evaluating their developed perfusion testing chamber. This research holds promise to lead to improved nanotherapeutics in the future. Read more: Lysyy, Taras, Laura G. Bracaglia, Lingfeng Qin, Claire Albert, Jordan S. Pober, George Tellides, W. Mark Saltzman, and Gregory T. Tietjen. "Ex vivo isolated human vessel perfusion system for the design and assessment of nanomedicines targeted to the endothelium." Bioengineering & Translational Medicine. https://aiche.onlinelibrary.wiley.com/doi/abs/10.1002/btm2.10154

“Abstract: Endothelial cells play a central role in the process of inflammation. Their biologic relevance, as well as their accessibility to IV injected therapeutics, make them a strong candidate for treatment with molecularly‐targeted nanomedicines. Typically, the properties of targeted nanomedicines are first optimized in vitro in cell culture and then in vivo in rodent models. While cultured cells are readily available for study, results obtained from isolated cells can lack relevance to more complex in vivo environments. On the other hand, the quantitative assays needed to determine the impact of NP design on targeting efficacy are difficult to perform in animal models. Moreover, results from animal models often translate poorly to human systems. To address the need for an improved testing platform, we developed an Isolated Vessel Perfusion System (IVPS) to enable dynamic and quantitative study of vascular‐targeted nanomedicines in readily obtainable human vessels isolated from umbilical cords or placenta. We show that this platform technology enables the evaluation of parameters that are critical to targeting efficacy (including flow rate, selection of targeting molecule, and temperature). Furthermore, biologic replicates can be easily produced by evaluating multiple vessel segments from the same human donor in independent, modular chambers. The chambers can also be adapted to house vessels of a variety of sizes, enabling subsequent study of vessel segments in vivo following transplantation into immunodeficient mice. We believe this perfusion system can help to address long‐standing issues in endothelial targeted nanomedicines and thereby enable more effective clinical translation.”

- Save-the-date: Akina, Inc's third annual Biotech-Pharma-Cancer-Research (BPCR) conference is August 26 at Kurz Purdue Technology Center (KPTC) (http://bpcrconference.com/).

- Notice: Akina, Inc. will be closed December 24th through January 1st for the holidays. Orders placed during this time will be processed when we re-open on Thursday, January 2, 2020.

PLGA From PolySciTech used in the development of photoluminescent nanoparticles for treatment and diagnosis of cardiovascular disease.

Tuesday, December 17, 2019, 4:07 PM ET

The leading cause of death worldwide is cardiovascular disease. Recently, researchers at The University of Texas at Arlington, Pennsylvania State University, VA North Texas Medical Center, and The University of Texas Southwestern Medical Center used PLGA (PolyVivo AP154) from PolySciTech (www.polyscitech.com) as part of developing a nanoparticle based therapy for this disease. This research holds promised for improved therapies against heart disease. Read more: Kuriakose, Aneetta E., Nikhil Pandey, Dingying Shan, Subhash Banerjee, Jian Yang, and Kytai T. Nguyen. "Characterization of Photoluminescent Polylactone-Based Nanoparticles for Their Applications in Cardiovascular Diseases." Frontiers in Bioengineering and Biotechnology 7 (2019). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6886382/

“Abstract: Cardiovascular diseases (CVD) affect a large number of the population across the globe and are the leading cause of death worldwide. Nanotechnology-based drug delivery has currently offered novel therapeutic options to treat these diseases, yet combination of both diagnostic and therapeutic abilities is further needed to understand factors and/or mechanisms that affect the treatment in order to design better therapies to challenge CVD. Biodegradable photoluminescent polylactones (BPLPLs) enable to bridge this gap as these materials exhibit a stable, long-term intrinsic fluorescence as well as offers excellent cytocompatibility and biodegradability properties. Herein, we formulated three different BPLPL based nanoparticles (NPs), including BPLP-co-poly (L-lactic acid) (BPLPL-PLLA), BPLP-co-poly (lactic-co-glycolic acid) copolymers with lactic acid and glycolic acid ratios of 75:25 (BPLPL-PLGA75:25) and 50:50 (BPLPL-PLGA50:50), and extensively evaluated their suitability as theranostic nanocarriers for CVD applications. All BPLPL based NPs were <160 2="" accumulation="" activation="" adhesion="" all="" an="" and="" approved="" as="" based="" be="" better="" bioimaging="" biological="" blood="" body="" bplp="" bplpl-based="" bplpl-plga="" bplpl-plla="" bplpl="" br="" cardiovascular="" carriers="" cell="" cells="" cellular="" characteristics="" comparable="" compared="" compatibility="" consisted="" copolymerized="" cvd.="" days.="" deionized="" demonstrated="" depending="" derived="" diagnosis="" disease="" displayed="" dose-dependent="" drug="" effect="" effects="" encapsulated="" endothelial="" excellent="" fda="" fluid="" for="" formulations="" functional="" functions="" furthermore="" had="" have="" hemocompatibility="" hence="" human="" in="" including="" keywords:="" kinetic="" kinetics="" material.="" materials.="" minimal="" model="" nanocarriers="" nitric="" nm="" no="" non-hemolytic="" nps="" of="" on="" our="" over="" overall="" oxide="" photoluminescence="" physical="" platelet="" plga="" polylactones="" potential="" presented="" production.="" profiles="" properties="" protein="" release="" responses="" results="" saline="" serum="" showed="" simulated="" size="" stability="" studies="" such="" superior="" terms="" than="" that="" theranostics="" therapy="" they="" those="" to="" toxicity="" tunable="" umbilical="" utilized="" various="" vascular="" vein="" viability="" vitro="" water="" were="" whole="" with="">
- Save-the-date: Akina, Inc's third annual Biotech-Pharma-Cancer-Research (BPCR) conference is August 26 at Kurz Purdue Technology Center (KPTC) (http://bpcrconference.com/).

- Notice: Akina, Inc. will be closed December 24th through January 1st for the holidays. Orders placed during this time will be processed when we re-open on Thursday, January 2, 2020.

PLGA from PolySciTech used in development of autonomous drug-delivery system for cancer therapy

Tuesday, December 17, 2019, 3:35 PM ET

Making sure medicines get to the location they need to be for their function is the key goal of drug-delivery. There are many methods to do this with including several bio-inspired and advanced methodologies have been sought as part of this. Recently, researchers at Virginia Tech and University of Oklahoma used PLGA (PolyVivo AP082) from PolySciTech (www.polyscitech.com) in their research on developing autonomous drug-delivery carriers. This research holds promise to provide for improved therapies against cancer and other diseases. Read more: Zhan, Ying, Austin Fergusson, Lacey R. McNally, Richey M. Davis, and Bahareh Behkam. "Effect of Assembly Method on Nanoparticle Attachment Density, Growth Rate, and Motility of Nanoscale Bacteria Enabled Autonomous Drug Delivery System (NanoBEADS)." bioRxiv (2019): 867101. (https://www.biorxiv.org/content/10.1101/867101v1.abstract)

"Abstract: Microbial-mediated drug delivery systems have the potential to significantly enhance the efficacy of nanomedicine for cancer therapy through improved specificity and interstitial transport. The Nanoscale Bacteria-Enabled Autonomous Drug Delivery System (NanoBEADS) is a bacteria-based bio-hybrid drug delivery system designed to carry nanotherapeutics cargo deep into poorly vascularized cancerous tissue. The effect of bacteria-nanoparticle conjugation method and NanoBEADS assembly parameters (i.e., mixing method, volume, and duration) was investigated to maximize particle attachment density. The nanoparticle attachment capacity, viability, growth rate and motility of the original NanoBEADS and an antibody-free variant NanoBEADS were characterized and compared. It is found that the assembly parameters affect the attachment outcome and the binding mechanism impacts the attachment number, the growth rate and motility of NanoBEADS. The NanoBEADS platform provides an opportunity to load nanoparticles with different materials and sizes for applications beyond cancer therapy, such as imaging agents for high resolution medical imaging."

- Save-the-date: Akina, Inc's third annual Biotech-Pharma-Cancer-Research (BPCR) conference is August 26 at Kurz Purdue Technology Center (KPTC).

- Notice: Akina, Inc. will be closed December 24th through January 1st for the holidays. Orders placed during this time will be processed when we re-open on Thursday, January 2, 2020.

PLGA from PolySciTech Used in Research on Nanoparticle Generation Methods

Tuesday, December 3, 2019, 10:00 AM ET

There are many methods to generate nanoparticles and they all vary based on the quality of the particles as well as the scalability and control of the method. Recently, researchers at American University of Sharjah (United Arab Emirates) used PLGA (AP154) from PolySciTech (www.polyscitech.com) to create nanoparticles according to several novel microfluidic and electrical methods. They recently published about these methods in a series of manuscripts and presentations. Read more:

Abualsayed, Alsaeed M., Sara A. Abouelmagd, and Mohamed Abdelgawad. "Miniaturised preparation of polymeric nanoparticles using droplet manipulation on open surfaces." Micro & Nano Letters 14, no. 13 (2019): 1312-1316. (https://digital-library.theiet.org/content/journals/10.1049/mnl.2019.0421) “Abstract: A digital microfluidics platform for the preparation of poly(lactic-co-glycolic) acid (PLGA) nanoparticles (NPs) was developed. Droplets of PLGA in dimethylformamide were merged with droplets of deionised water by electrical actuation on a digital microfluidics device to form PLGA NPs through nanoprecipitation. The developed platform is automated and allows for the preparation of polymeric NPs with small size and high uniformity. Using the platform, the authors were able to prepare monodisperse PLGA NPs as small as 115 nm with a polydispersity index (PDI) of 0.14 which can be challenging with conventional preparation techniques on the macroscale. Size of the prepared NPs can be tuned through proper choice of the volume ratio between the two merged droplets which controls the induced internal convection flow after merging. Concentration of PLGA in the dimethylformamide droplet also had an effect on the size and polydispersity of the formed NPs. These results prove the potential use of digital microfluidics for testing combinatorial synthesis of different polymeric NPs for various applications. This approach allows robust and automated screening of NP preparations using only few microlitres of the reagents used, thus conserving precious and costly NP components and loaded therapeutic agents.”

Abualsayed, Alsaeed, Sara Abouelmagd, and Mohamed Abdelgawad. "Nanoparticles synthesis using digital microfluidics." In 2019 IEEE 14th International Conference on Nano/Micro Engineered and Molecular Systems (NEMS), pp. 201-204. IEEE, 2019. (https://ieeexplore.ieee.org/abstract/document/8915616/) “Abstract: We developed a Digital Microfluidics platform for synthesis of Poly(Lactic-co-glycolic) acid (PLGA) Nanoparticles (NPs). As far as we know, it is the first time droplet manipulation on open surfaces is used in NP synthesis. The platform we developed is automated and allows for synthesis of polymeric NPs with smaller size and higher uniformity. Using our platform, we were able to prepare monodisperse PLGA NPs as small as 115 nm with a polydispersity index (PDI) of 0.14 which can be challenging with conventional preparation techniques on the macroscale. Size of the prepared NPs was found to decrease with increasing the volume ratio between the water droplet and the dimethylformamide-PLGA droplet merged on the device. Increasing the concentration of PLGA resulted in larger particle size and smaller PDI. We believe our results prove the potential use of digital microfluidics for testing combinatorial synthesis of different polymeric NPs for various applications.”

PLGA-PEG-PLGA Thermogel from PolySciTech Used in Development of Spinal Cord Injury Treatment

Tuesday, December 3, 2019, 9:59 AM ET

Traumatic injuries to the spinal column typically occur due to trauma (vehicular/sports accident) which damages or severs the nerves in the spine. Since neural tissue does not repair itself the same way as other tissues, many of these injuries result in a lifetime of paralysis. Recently, researchers at New York University School of Medicine and Qingdao University (China) used PLGA-PEG-PLGA thermogel (AK097) from PolySciTech (www.polyscitech.com) to create a Atsttrin (a progranulin (PGRN) derivative) delivery gel for treatment of spinal cord injury. This research holds promise to repair neural damage and may potentially be used as part of treatment for injury induced paralysis. Read more: Wang, Chao, Lu Zhang, Jean De La Croix Ndong, Aubryanna Hettinghouse, Guodong Sun, Changhong Chen, Chen Zhang, Ronghan Liu, and Chuan-ju Liu. "Progranulin deficiency exacerbates spinal cord injury by promoting neuroinflammation and cell apoptosis in mice." Journal of Neuroinflammation 16, no. 1 (2019): 1-12. https://link.springer.com/article/10.1186/s12974-019-1630-1

“Abstract: Purpose: Spinal cord injury (SCI) often results in significant and catastrophic dysfunction and disability and imposes a huge economic burden on society. This study aimed to determine whether progranulin (PGRN) plays a role in the progressive damage following SCI and evaluate the potential for development of a PGRN derivative as a new therapeutic target in SCI. Methods: PGRN-deficient (Gr−/−) and wild-type (WT) littermate mice were subjected to SCI using a weight-drop technique. Local PGRN expression following injury was evaluated by Western blotting and immunofluorescence. Basso Mouse Scale (BMS), inclined grid walking test, and inclined plane test were conducted at indicated time points to assess neurological recovery. Inflammation and apoptosis were examined by histology (Hematoxylin and Eosin (H&E) staining and Nissl staining, TUNEL assays, and immunofluorescence), Western blotting (from whole tissue protein for iNOS/p-p65/Bax/Bcl-2), and ex vivo ELISA (for TNFα/IL-1β/IL-6/IL-10). To identify the prophylactic and therapeutic potential of targeting PGRN, a PGRN derived small protein, Atsttrin, was conjugated to PLGA-PEG-PLGA thermosensitive hydrogel and injected into intrathecal space prior to SCI. BMS was recorded for neurological recovery and Western blotting was applied to detect the inflammatory and apoptotic proteins. Results: After SCI, PGRN was highly expressed in activated macrophage/microglia and peaked at day 7 post-injury. Grn−/− mice showed a delayed neurological recovery after SCI at day 21, 28, 35, and 42 post-injury relative to WT controls. Histology, TUNEL assay, immunofluorescence, Western blotting, and ELISA all indicated that Grn−/− mice manifested uncontrolled and expanded inflammation and apoptosis. Administration of control-released Atsttrin could improve the neurological recovery and the pro-inflammatory/pro-apoptotic effect of PGRN deficiency. Conclusion: PGRN deficiency exacerbates SCI by promoting neuroinflammation and cellular apoptosis, which can be alleviated by Atsttrin. Collectively, our data provide novel evidence of using PGRN derivatives as a promising therapeutic approach to improve the functional recovery for patients with spinal cord injury. Keywords: Progranulin Inflammation Apoptosis Spinal cord injury”

PLGA-PEG-PLGA Thermogelling polymers from PolySciTech used In Development of Hyaluronic Acid Delivery System.

Friday, November 22, 2019, 1:45 PM ET

Block copolymers can be used to develop thermogelling systems which are liquid at cold temperatures and turn solid when the temperature increases. One practical application of this phenomenon is drug delivery in which a cold solution of the polymer and a drug are injected into a patient and then the polymer solidifies around the drug upon heating to the patient’s body temperature (37C/98.6F) to delay and control its release rate. Recently, researchers at Rowan University used several PLGA-PEG-PLGA polymers (AK097, AK088, AK085, AK091, etc.) from PolySciTech (www.polyscitech.com) to develop a thermogelling system for the ocular delivery of hyaluronic acid. This research holds promise for the development of thermogelling drug-delivery systems. Read more: Osorno, Laura L., Daniel E. Maldonado, Ricky J. Whitener, Alyssa N. Brandley, Alex Yiantsos, Jamie DR Medina, and Mark E. Byrne. "Amphiphilic PLGA‐PEG‐PLGA triblock copolymer nanogels varying in gelation temperature and modulus for the extended and controlled release of hyaluronic acid." Journal of Applied Polymer Science (2019). https://onlinelibrary.wiley.com/doi/abs/10.1002/app.48678

“ABSTRACT: Different compositional parameters of poly(D,L‐lactic‐co‐glycolic acid)‐b‐poly(ethylene glycol) triblock copolymers (PLGA‐PEG) were varied to analyze their effect on gel formation and mechanical properties. Parameters such as hydrophilic/hydrophobic ratio (PLGA/PEG ratio), lactic acid/glycolic acid ratio (LA/GA ratio), PEG molecular weight (PEG Mw), polymer solution concentration, copolymer molecular weight (Mw), and polydispersity index (PDI) were studied in this work. For copolymers with PEG Mw of 1500 Da, gelation temperature (34–37 °C) was affected by D,L‐LA/GA ratio and Mw; while modulus was affected by LA/GA ratio, Mw, and Mn. Based on the parametric study, an injectable, thermoresponsive hyaluronic acid (HA) delivery platform was designed for ocular applications. PLGA‐PEG copolymers with D,L‐LA/GA ratio of 15/1, PLGA/PEG ratio of 2/1, PEG Mw of 1500 Da, and Mw of about 6 KDa gelled at 35 °C, were optically transparent, had a modulus less than 350 Pa and were used for HA release studies. This work also demonstrates, for the first time, an extended and controlled release of HA, beyond 2 weeks, from injectable hydrogels modified with a noncovalent interacting agent, poly(L‐lysine). Smaller PLL chains slowed down the HA release kinetics, while larger PLL chains produced a release profile similar to the nonmodified hydrogels. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019, 137, 48678.”

Technical White-Paper on PLGA/PLA/PLCL degradation properties available from PolySciTech

Friday, November 22, 2019, 1:40 PM ET

Biodegradable polymers such as PLGA are all alkyl polyesters which undergo hydrolysis to break down into residues and oligomers. The time over which this process occurs varies widely based on the molecular weight and chemical makeup (LA:GA ratio, etc.) of the polymers. Recently, PolySciTech (www.polyscitech.com) concluded a 9-month study on select polymers (AP081, AP086, AP089, AP091, AP120, AP136, AP178, and AP190) tracking their mass loss and molecular weight changes as they degraded in water at 37 ⁰C. The results of this degradation study can be seen on the technical white-paper here (http://akinainc.com/pdf/Whitepaper-polymer-degradation.pdf).

PLGA from PolySciTech used in optimization of nanoparticle encapsulation of chemotherapeutic agent.

Tuesday, November 12, 2019, 11:27 AM ET

The single-emulsion technique is a widely used methodology to form nanoparticles when the drug to be loaded is hydrophobic enough to be directly dissolved into the organic solvent along with the polymer. The exact size and loading efficiency of these particles varies based on the manufacturing parameters and these can be optimized to provide for the highest quality nanoparticles. Recently, researchers at University of Houston used PLGA (AP041) from PolySciTech (www.polyscitech.com) and single-emulsion based techniques to optimize the nanoparticle encapsulation method for a chemotherapy drug. This research holds promise for improved therapy against cancer. Read more: Holley, Claire K., Bridgett Sinquefield, and Sheereen Majd. "Optimization of the Single Emulsion Method for Encapsulation of a Cancer Drug in Nanoparticles." In 2019 41st Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC), pp. 1078-1081. IEEE, 2019. https://ieeexplore.ieee.org/abstract/document/8857458/

“Abstract: The goal of this study is to apply and optimize the single emulsion technique for encapsulation of an anti-tumor drug, Di-2-pyridylketone-4,4-dimethyl-3-thiosemicarbazone (Dp44mT), in nanoparticles (NPs) of poly(lactic-co-glycolic acid) (PLGA), as a step towards targeted delivery of this drug. We previously showed that the nanoprecipitation technique can effectively produce PLGA NPs carrying this drug. Here, we aim to examine the single emulsion technique as an alternative for the preparation of these NPs and to compare the resultant NPs to those from nanoprecipitation. We fabricated NPs with variations in (i) injection rate, (ii) the amount of surfactant poly (vinyl alcohol) (PVA) in aqueous phase, and (iii) concentration of PLGA in the organic phase. These NPs were characterized for size, surface potential, and encapsulation efficiency. The results revealed that increasing the injection rate (from manual addition to 90 mL/hr via syringe pump) greatly reduced the size of NPs (by 48%) and decreasing the PVA concentration in the aqueous phase (from 5 to 1% w/v) further reduced the NP size (by 32%) to 329 nm. All tested NP formulations had negative surface potential, suggesting good colloidal stability for these NPs. Focusing on the optimal injection rate and PVA percentage, we found that reducing the concentration of PLGA, from 100 to 1 mg/mL, significantly reduced the NP size to 136 nm, which is close to the optimal range for cancer therapeutic delivery. NPs produced by this method had a high encapsulation efficiency of 77% for Dp44mT and reducing the PLGA concentration slightly lowered this value to 74%. Overall, these NPs were comparable to those produced by nanoprecipitation and can thus, serve as an effective alternative for delivery of Dp44mT to cancer cells.”

mPEG-PLA and PLA-PEG-COOH from PolySciTech used in development of prostate cancer therapy

Tuesday, November 12, 2019, 11:26 AM ET

Ensuring appropriate delivery of drug molecules to the location of action is critical for their efficacy. Prostate cancer is one of the most common types of cancer in men and can be aggressive and spread. This type of cancer can be targeted by a specific antigen. Recently, researchers at Mashhad University of Medical Sciences (Iran) used mPEG-PLA (AK054) and PLA-PEG-COOH (AI030) from PolySciTech (www.polyscitech.com) to create galbanic acid/docetaxel loaded nanoparticles decorated with a targeting molecule for prostate cancer treatment. This research holds promise to provide for improved therapies against this common type of cancer. Read more: Afsharzadeh, Maryam, Maryam Hashemi, Maryam Babaei, Khalil Abnous, and Mohammad Ramezani. "PEG‐PLA nanoparticles decorated with small‐molecule PSMA ligand for targeted delivery of galbanic acid and docetaxel to prostate cancer cells." Journal of cellular physiology (2019). https://onlinelibrary.wiley.com/doi/abs/10.1002/jcp.29339

“Abstract: Prostate cancer (PCa) is one of the most prevalent non‐drug delivery system cutaneous malignancies. Undoubtedly, introducing novel treatment options to achieve higher therapeutic index will be worthwhile. In this study, we report for the first time, a novel targeted self‐assembled based on PEG‐PLA nanoparticles (PEG‐PLA NPs) containing galbanic acid (GBA) and docetaxel, which was targeted using ((S)‐2‐(3‐((S)‐5‐amino‐1‐carboxypentyl) ureido) pentanedioic acid (ACUPA), a small molecule inhibitor targeting prostate‐specific membrane antigen (PSMA), in prostate cancer cell line. The prepared NPs were characterized by different analytical methods. The MTT assay was used to compare the anti‐proliferation of drugs‐loaded PEG‐PLA NPs and ACUPA‐PEG‐PLA against LNCaP (PSMA+) and PC3 (PSMA−) cells. PEG‐PLA NPs with an average size of 130–140 nm had an enhanced release of GBA and docetaxel at pH 5.5 compared with pH 7.5. Spectrofluorometric analysis suggested that ACUPA‐modified PEG‐PLA could effectively enhance the drug uptake in PSMA+ prostate cancer cells. Cytotoxicity studies showed that the targeted NPs loaded with different concentrations of GBA and fixed concentration of docetaxel (4 nM) have shown higher toxicity (IC50 30 ± 3 µM) than both free GBA (80 ± 4.5 µM) and nontargeted NPs (IC50 40 ± 4.6 µM) in LNCaP cells. Collectively, these findings suggest that ACUPA‐conjugated PEG‐PLA nanosystem containing GBA and docetaxel is a viable delivery carrier for various cancer‐targeting PSMA that suffer from short circulation half‐life and limited therapeutic efficacy.”

mPEG-PLA from PolySciTech used in development of continuous nanoparticle generation system for large-scale nanoparticle production

Friday, November 1, 2019, 3:09 PM ET

Nanoparticles are generated by the carefully controlled solvent extraction of a polymer solution under emulsifying conditions which causes the polymer to self-form into small spheres (nanoparticles). There are many ways to generally accomplish this, however most have to be done in batch mode and are limited in scale. Recently, researchers at ETH Zurich (Switzerland) used mPEG-PLA (AK056) from PolySciTech (www.polyscitech.com) for generation of nanoparticles using a novel coaxial mixing system which can rapidly generate large quantities of particles. This research holds promise to enable large-scale production of nanoparticles. Read more: Bovone, Giovanni, Elia A. Guzzi, and Mark W. Tibbitt. "Flow‐based reactor design for the continuous production of polymeric nanoparticles." AIChE Journal (2019). https://aiche.onlinelibrary.wiley.com/doi/abs/10.1002/aic.16840

“Abstract: Polymeric nanoparticles (NPs) are versatile and effective drug delivery systems (DDS) that can be produced via nanoprecipitation of block copolymers. Yet, translation into clinical products has been limited. Thus, methods for NP production that enable rapid formulation screening and continuous production are needed. Toward this end, we engineered a coaxial jet mixer (CJM) for controlled and continuous nanoprecipitation in flow. The CJM enabled continuous assembly of poly(ethylene glycol)‐block‐polylactide NPs with various co‐solvents and was compared to batch nanoprecipitation. Other fabricated microfluidic devices were suitable for small scale formulation screening but more limited in scalable and continuous processes. In contrast, the CJM was tolerant to all water‐miscible solvents tested, enabled formulation screening, and scalable production of NPs and DDS. In total, the CJM provides a complementary approach to the process engineering of polymeric NP formation that can be used broadly for formulation screening and production.”

PLGA from PolySciTech used in study on nanoparticle biodistribution based on particle size.

Friday, November 1, 2019, 3:09 PM ET

When nanoparticles are injected into a body several competing forces come into play which drive their motion. There are many features which affect this localization one of which is relative size of the particles. Recently, researchers at Yale University used PLGA (AP041) from PolySciTech (www.polyscitech.com) for generation of nanoparticles. These were then used to track their biodistribution across living systems to determine which organs/tissues they primarily transported too. This research holds promise to enable future developments of tissue-targeted nanoparticles based on particle size. Read more: Mandl, Hanna K., Elias Quijano, Hee Won Suh, Emily Sparago, Sebastian Oeck, Molly Grun, Peter M. Glazer, and W. Mark Saltzman. "Optimizing Biodegradable Nanoparticle Size for Tissue-Specific Delivery." Journal of Controlled Release (2019). https://www.sciencedirect.com/science/article/pii/S0168365919305589

“Abstract: Nanoparticles (NPs) are promising vehicles for drug delivery because of their potential to target specific tissues [1]. Although it is known that NP size plays a critical role in determining their biological activity, there are few quantitative studies of the role of NP size in determining biodistribution after systemic administration. Here, we engineered fluorescent, biodegradable poly(lactic-co-glycolic acid) (PLGA) NPs in a range of sizes (120–440 nm) utilizing a microfluidic platform and used these NPs to determine the effect of diameter on bulk tissue and cellular distribution after systemic administration. We demonstrate that small NPs (∼120 nm) exhibit enhanced uptake in bulk lung and bone marrow, while larger NPs are sequestered in the liver and spleen. We also show that small NPs (∼120 nm) access specific alveolar cell populations and hematopoietic stem and progenitor cells more readily than larger NPs. Our results suggest that size of PLGA NPs can be used to tune delivery to certain tissues and cell populations in vivo.”

These posts are syndicated from John Garner's blog at http://jgakinainc.blogspot.com/ where you can post a question or comment. (Load took 0.5477340221405 seconds)


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