Tuesday, February 25, 2020

PLGA from PolySciTech used in development of long-acting ocular implant


Intravitreal injections can be sight-saving as they are used to prevent the progression of macular degeneration and other ocular diseases. Although effective, this therapy requires repeated intra-ocular injections which is inconvenient for both patient and clinician. Recently, researchers at University of Cincinnati used PLGA (AP119) from PolySciTech (www.polyscitech.com) to create a nanoporous implant for controlled drug delivery to the eye. This research holds promise for development of a sight-saving therapy with fewer injections. Read more: He, Xingyu, Zheng Yuan, Winston W. Kao, Daniel M. Miller, S. Kevin Li, and Yoonjee C. Park. "Size-Exclusive Nanoporous Biodegradable PLGA Capsule for Drug Delivery Implant and The In Vivo Stability In The Posterior Segment." ACS Applied Bio Materials (2020). https://pubs.acs.org/doi/abs/10.1021/acsabm.0c00027

“Abstract: The current standard of care for posterior segment eye diseases such as neovascular age-related macular degeneration, diabetic macular edema is frequent intravitreal injections or sustained-release drug implants. Intravitreal injections have a low incidence of serious complications such as retinal detachment, endophthalmitis, iatrogenic traumatic cataract, or iridocyclitis and injection-site reactions. However, there is a significant burden to the patient, the patient’s family, and the health system because current intravitreal therapies require between every 4 and 12 week administration over many years. Drug implants have side effects due to burst release of the drugs and their release cannot be easily controlled after implantation. We have developed a size-exclusive nanoporous biodegradable PLGA capsule for dosage-controllable drug delivery implants. We have optimized the nanoporous structure by tuning the ratio between porogen and high molecular weight PLGA and tested the stability against passive leakage of liposomal drug (1~2 μm) and the safety in vivo rabbit eyes for 6 months. Our results suggest that PLGA implants made of the nanoporous PLGA sheet can selectively release drug molecules, keeping the liposomal drug inside. In addition, the implant was biocompatible causing no inflammation and foreign body response when implanted for 6 months. Overall, the implant shows a great potential for on-demand dose-controllable drug release 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/).

Thursday, February 20, 2020

PLGA from PolySciTech used in development of nanoparticle system for lung-cancer


Many chemotherapeutic agents, such as cisplatin, are highly toxic which limits the dose due to side effects. A delivery system which can improve the amount of drug which actually releases in the tumor site would improve this. Recently, researchers at University of Texas used PLGA (AP154) from PolySciTech (www.polyscitech.com) was used to create cisplatin-loaded PLGA nanoparticles for comparison to novel PEU nanoparticles. This research holds promise to provide for improved therapies against lung cancer. Read more: Iyer, Roshni, Tam Nguyen, Dona Padanilam, Cancan Xu, Debabrata Saha, Kytai T. Nguyen, and Yi Hong. "Glutathione-responsive biodegradable polyurethane nanoparticles for lung cancer treatment." Journal of Controlled Release (2020). https://www.sciencedirect.com/science/article/pii/S0168365920301115

“Highlights: Glutathione is abundantly available in lung cancer microenvironment. Biodegradable polyurethane nanoparticles were fabricated via a single emulsion with a mixed organic solvent. GSH-sensitive biodegradable polyurethane nanoparticles (GPUs) released encapsulated cisplatin in response to elevated glutathione levels. Cisplatin loaded GPUs significantly reduced tumor growth in a subcutaneously xenograft A549 lung tumor mouse model compared to the free cisplatin. Abstract: Lung cancer is one of the major causes of cancer-related deaths worldwide. Stimuli-responsive polymers and nanoparticles, which respond to exogenous or endogenous stimuli in the tumor microenvironment, have been widely investigated for spatiotemporal chemotherapeutic drug release applications for cancer chemotherapy. We developed glutathione (GSH)-responsive polyurethane nanoparticles (GPUs) using a GSH-cleavable disulfide bond containing polyurethane that responds to elevated levels of GSH within lung cancer cells. The polyurethane nanoparticles were fabricated using a single emulsion and mixed organic solvent method. Cisplatin-loaded GSH-sensitive nanoparticles (CGPU) displayed a GSH-dose dependent release of cisplatin. In addition, a significant reduction in in vitro survival fraction of A549 lung cancer cells was observed compared to free cisplatin of equivalent concentration (survival fraction of ~0.5 and ~0.7, respectively). The in vivo biodistribution studies showed localization of fluorescently labeled GPUs (~7% of total injected dose) in the lung tumor regions after mouse-tail IV injections in xenograft A549 lung tumor models. The animals exposed to CGPUs also exhibited the inhibition of lung tumor growth compared to animals administered with saline (tumor growth rate of 1.5 vs. 13 in saline) and free cisplatin (tumor growth rate of 5.9) in mouse xenograft A549 lung tumor models within 14 days. These nanoparticles have potential to be used for on-demand drug release for an enhanced chemotherapy to effectively treat lung 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/).

Thursday, February 13, 2020

PLGA from PolySciTech used in evaluation of 3D Cell culturing of cancer cells as assay tool.



Testing cancer therapies requires making sure that the test used is relevant to the physiology of the patient. Ideally, cancer cells will be grown in a 3D format, same as they are in the human body. Recently, researchers at San Jose State University used PLGA (AP042) from PolySciTech (www.polyscitech.com) to create doxorubicin nanoparticles for testing the accuracy of 3D Cell cultures. This research holds promise for improved research in cancer therapy in the future. Read more: Nimbalkar, Priya, Peter Tabada, Anuja Bokare, Jeffrey Chung, Marzieh Mousavi, Melinda Simon, and Folarin Erogbogbo. "Improving the physiological relevance of drug testing for drug-loaded nanoparticles using 3D tumor cell cultures." MRS Communications 9, no. 3 (2019): 1053-1059. https://www.cambridge.org/core/journals/mrs-communications/article/improving-the-physiological-relevance-of-drug-testing-for-drugloaded-nanoparticles-using-3d-tumor-cell-cultures/FEAC0E69F94D331886A06FFD2E854D0A

Nanoparticle-mediated drug delivery has the potential to overcome several limitations of cancer chemotherapy. Lipid polymer hybrid nanoparticles (LPHNPs) have been demonstrated to exhibit superior cellular delivery efficacy. Hence, doxorubicin (a chemotherapeutic drug)-loaded LPHNPs have been synthesized by three-dimensional (3D)-printed herringbone-patterned multi-inlet vortex mixer. This method offers rapid and efficient mixing of reactants yielding controllable and reproducible synthesis of LPHNPs. The cytotoxicity of LPHNPs is tested using two-dimensional (2D) and 3D microenvironments. Results obtained from 3D cell cultures showed major differences in cytotoxicity in comparison with 2D cultures. These results have broad implications in predicting in vitro LPHNP toxicology.

--> 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 development of simvastatin delivery system to treat neuroinflammation.

Inflammation is a natural response to injury or infection which can also lead to significant health problems. Recently, researchers at Kent State University used mPEG-PLA (AK021) from PolySciTech (www.polyscitech.com) to create nanoparticles for intraceullular delivery of anti-inflammatory agents. This research holds promise to treate a variety of inflammatory-related disease states. Read more: Manickavasagam, Dharani, and Moses O. Oyewumi. "Internalization of particulate delivery systems by activated microglia influenced the therapeutic efficacy of simvastatin repurposing for neuroinflammation." International Journal of Pharmaceutics 570 (2019): 118690. https://www.sciencedirect.com/science/article/pii/S0378517319307355

“Abstract: We recently evaluated the suitability of polymersome delivery systems in simvastatin repurposing for treating neuroinflammation. The goal of the current study is to elucidate the therapeutic impact of particulate internalization by activated microglia on the resultant anti-inflammatory properties. Thus, we investigated the endocytic mechanism(s) involved in uptake and transport of simvastatin-loaded polymersomes by BV2 microglia cells coupled with delineation of the intracellular pathway(s) involved in regulating anti-inflammatory effects. Our data indicated that internalization of polymersome delivery systems by activated microglial BV2 cells was important in the suppression of nitric oxide (NO), TNF-α and IL-6 production. Further, we observed that the lipid raft/caveolae pathway had the most influential effect on polymersome internalization by microglia cells while clathrin-mediated endocytosis did not play a major role. Enhancement of anti-inflammatory effects of simvastatin could be attributed to inhibition of ERK1/2, JNK and AKT signaling pathways and internalization of polymersome delivery systems in activated microglia. Taken together, our data provided insights into how the intracellular trafficking of delivery systems by microglial could be a useful tool in modulating the desired anti-inflammatory effects of drugs.”

--> 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-rhodamine from PolySciTech used in development of antibacterial nanoparticles

Bacteria have many survival strategies one of which is to hide inside of cells. Recently, researchers at Purdue University and Assiut University used PLGA-Rhodamine (AV011) and PLGA (AP020) from PolySciTech (www.polyscitech.com) to create fluorescent nanoparticles with antimicrobial peptides. These particles were found to be effective against intracellular bacteria. This research holds promise to provide for improved therapies against bacterial infections. Read more. G Elnaggar, Marwa, Hesham M Tawfeek, Aly A. Abdel-Rahman, E. Aboutaleb Ahmed, and Yoon Yeo. "Encapsulation Of Antennapedia (Penetratin) Peptide in a Polymeric Platform For Effective Treatment of Intracellular Bacteria." Bulletin of Pharmaceutical Sciences. Assiut 42, no. 1 (2019): 63-70. http://bpsa.journals.ekb.eg/article_62266.html

“Abstract: Antimicrobial peptides (AMP) and cell-penetrating peptides (CPP) are two classes of peptides that share some structural and physicochemical similarities. Antennapedia or penetratin (ANT) is one of the most known CPPs, that was proven to have antimicrobial activity against certain strains of planktonic bacteria. ANT can enter the cells but has no activity against intracellular bacteria. This is attributable to the inability of the peptide to reach bacteria reside within cellular components as well as low delivery efficiency, due to loss of activity by proteolysis and poor specificity. The aim of this work is to develop a formulation that can effectively reach and attack intracellular bacteria. To achieve this goal, ANT was encapsulated in PLGA platform as nanoparticles with the size range of 500-1000 nm, which allows for selective uptake by macrophages where bacteria mostly reside. ANT was loaded with high loading efficiency (12.7%) inspite of high water solubility. ANT-nanoparticles (ANT-NP) had no cytotoxicity on J774a.1 macrophages and were readily taken up by macrophages as confirmed by fluorescence microscopy. Antibacterial activity of ANT-NP remains to be tested against different intracellular bacteria.”

--> 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 imaging agent for evaluation of Transarterial chemoembolization for liver cancer treatment

Treatment of liver cancer often involves transcatheter embolization in which the artery that feeds the tumor area is sealed off to kill the cancer cells. Determining the success of the procedure requires being able to visualize if the region is correctly occluded or not which needs a suitable contrast/imaging agent. Recently, researchers from Southern University of Science and Technology, Henan University, Southern Medical University (China), and National University of Singapore used PLA (AP004) from PolySciTech to create fluorscent nanoparticles for visualizing the interior of decularilzed liver vascular structure. This research holds promise to improve the tools used to evaluate embolization procedures as part of treatment of liver cancer. Read more: Gao, Yanan, Zhihua Li, Yin Hong, Tingting Li, Xiaoyan Hu, Luyao Sun, Zhengchang Chen et al. "Decellularized liver as a translucent ex vivo model for vascular embolization evaluation." Biomaterials (2020): 119855. https://www.sciencedirect.com/science/article/pii/S0142961220301010

“Abstract: Transarterial chemoembolization (TACE) is the preferred treatment for patients with unresectable intermediate stage hepatocellular carcinoma, however currently the development of embolic agents for TACE lacks in vitro models that closely represent the sophisticated features of the organ and the vascular systems therein. In this study, we presented a new strategy using an ex vivo liver model to provide a translucent template for evaluating embolic agents of TACE. The ex vivo liver model was developed through decellularizion of rat liver organs with preserved liver-specific vasculatures and improved transmittance of the whole liver up to 23% at 550 nm. Using this model, we investigated the embolization performances of both liquid and particle-based embolic agents, including penetration depth, embolization end-points, injection pressure and spatial distribution dynamics. We found that the embolization endpoint of liquid embolic agent such as ethiodised oil was strongly dependent on the injection pressure, and the pressure quickly built up when reaching the capillary endings, which could cause embolic agent leaking and potential tissue damages. In contrast, for particle-based embolic agents such as poly-dl-lactide microparticles and CalliSpheres® beads, their embolization endpoints were mainly determined by the particle size, whereas the particle densities close to the endpoints dramatically dropped down, which with the penetration depth represented two critical factors determining the embolic distribution. Such a decellularized organ model may open a new route to visually and quantitatively characterize embolization effects of various embolotherapies. Keywords: Transarterial chemoembolization Embolic agents Decellularized liver matrix Vascular system Injection pressure”

--> 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-PLGA from PolySciTech used in development of griffithsin-based system to prevent the spread of sexually transmitted diseases.



HIV is a lethal disease which affects approximately 37.9 million people worldwide with (2018) leading to 770,000 deaths. Although less lethal, herpes is extremely common and, in the USA, roughly 25% of the population has genital herpes. Recently, researchers from University of Louisville used mPEG-PLGA (AK148) from PolyScitech (www.polyscitech.com) to generate drug-loaded fibers for protection against HIV and herpes infections. This research holds promise to provide a system which can prevent the spread of sexually transmitted diseases. Read more: Tyo, Kevin M., Amanda B. Lasnik, Longyun Zhang, Mohamed Mahmoud, Alfred B. Jenson, Joshua L. Fuqua, Kenneth E. Palmer, and Jill M. Steinbach-Rankins. "Sustained-release Griffithsin nanoparticle-fiber composites against HIV-1 and HSV-2 infections." Journal of Controlled Release (2020). https://www.sciencedirect.com/science/article/pii/S0168365920300857

“Highlights: Multilayered nanoparticle (NP)-electrospun fiber (EF) composites provided sustained-release of Griffithsin (GRFT). GRFT NPs and NP-EFs demonstrated in vitro efficacy against HIV-1 infection. NP-EF composites prevented lethal HSV-2 infection in a murine model. NP-EFs and NPs demonstrated preliminary safety in vivo, inducing negligible cytokine expression and inflammatory response. Abstract: Human immunodeficiency virus (HIV-1) and herpes simplex virus 2 (HSV-2) affect hundreds of millions of people worldwide. The antiviral lectin, Griffithsin (GRFT), has been shown to be both safe and efficacious against HSV-2 and HIV-1 infections in vivo. The goal of this work was to develop a multilayered nanoparticle (NP)-electrospun fiber (EF) composite to provide sustained-release of GRFT, and to examine its safety and efficacy in a murine model of lethal HSV-2 infection. Composites were fabricated from polycaprolactone (PCL) fibers surrounding polyethylene oxide (PEO) fibers that incorporated methoxy poly(ethylene glycol)-b-poly(lactide-co-glycolide) (mPEG-PLGA) GRFT NPs. GRFT loading and release were determined via ELISA, showing that NP-EF composites achieved high GRFT loading, and provided sustained-release of GRFT for up to 90 d. The in vitro efficacy of GRFT NP-EFs was assessed using HIV-1 pseudovirus assays, demonstrating complete in vitro protection against HIV-1 infection. Additionally, sustained-release NP-EFs, administered 24 h prior to infection, prevented against a lethal dose of HSV-2 infection in a murine model. In parallel, histology and cytokine expression from murine reproductive tracts and vaginal lavages collected 24 and 72 h post-administration were similar to untreated mice, suggesting that NP-EF composites may be a promising and safe sustained-delivery platform to prevent HSV-2 infection. Future work will evaluate the ability to provide prolonged protection against multiple virus challenges, and different administration times with respect to infection.”

--> 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/)