Journal
BIOMATERIALS SCIENCE
Volume 8, Issue 15, Pages 4308-4321Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/d0bm00596g
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Funding
- Early Career Research Award (Science and Engineering Research Board, Department of Science and Technology, India) [ECR/2017/002178]
- Har Gobind Khorana Innovative Young Biotechnologist Award (Department of Biotechnology, India) [BT/12/IYBA/2019/04]
- Indian Institute of Science, Bangalore
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Osteoarthritis (OA) is a joint disease characterized by progressive damage of articular cartilage and the adjoining subchondral bone. Chondrocytes, the primary cells of the cartilage, have limited regenerative capacity and when they undergo stress due to trauma or with aging, they senesce or become apoptotic. Rapamycin, a potent immunomodulator, has shown promise in OA treatment. It activates autophagy 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. Here, 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 the drug for several weeks. Rapamycin microparticles protectedin vitrocartilage mimics (micromass cultures) from degradation, allowing sustained production of sGAG, and demonstrated a prolonged senescence preventive effect under oxidative and genomic stress conditions. These microparticles also exhibited a residence time of similar to 30 days after intra-articular injections in murine knee joints. Such particulate systems are promising candidates for intra-articular delivery of rapamycin for the treatment of osteoarthritis.
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