Wednesday, May 13, 2020

PLGA from PolySciTech used in development of Rapamycin-delivery microparticles for arthritis treatment

Arthritis is a disease driven by several causes but categorized by an immune response in the cartilidge which leads to damage of the tissue. Rapamycin modulates this immune response and can reduce the progression of arthritis. Recently, researchers at Indian Institute of Science (India) used PLGA (AP041) from PolySciTech (www.polyscitech.com) to develop Rapamycin-releasing microparticles. This research holds promise to provide for treatment against arthritis. Read more: Dhanabalan, Kaamini M., Vishal K. Gupta, and Rachit Agarwal. "Rapamycin-PLGA microspheres induce autophagy and prevent senescence in chondrocytes and exhibit long in vivo residence." bioRxiv (2020). https://www.biorxiv.org/content/10.1101/2020.04.06.027136v1.abstract

“Osteoarthritis (OA) is a joint disease that results in progressive destruction of articular cartilage and the adjoining subchondral bone. The current treatment is focused on symptomatic relief due to the absence of disease-modifying drugs. The primary cells of the cartilage, chondrocytes, have limited regenerative capacity and when they undergo stress due to trauma or with aging, they senesce or become apoptotic. Autophagy, a cellular homeostasis mechanism has a protective role in OA during stress but gets downregulated in OA. Rapamycin, a potent immunomodulator, has shown promise in OA treatment by autophagy activation and is known to prevent senescence. However, its clinical translation for OA is hampered due to systemic toxicity as high and frequent doses are required. Hence, there is a need to develop suitable delivery carriers that can result in sustained and controlled release of the drug in the joint. In this study, we have fabricated rapamycin encapsulated poly (lactic-co-glycolic acid) (PLGA) based carriers that induced autophagy and prevented cellular senescence in human chondrocytes. The microparticle (MP) delivery system showed sustained release of drug for several weeks. Rapamycin-microparticles protected in-vitro cartilage mimics from degradation, allowing sustained production of sGAG, and demonstrated a prolonged senescence preventive effect in vitro under oxidative and genomic stress conditions. These microparticles also exhibited a long residence time of more than 19 days in the joint after intra-articular injections in murine knee joints. Such particulate systems are a promising candidate for intra-articular delivery of rapamycin for treatment of osteoarthritis.”

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