MilliporeSigma
  • Rapamycin-PLGA microparticles prevent senescence, sustain cartilage matrix production under stress and exhibit prolonged retention in mouse joints.

Rapamycin-PLGA microparticles prevent senescence, sustain cartilage matrix production under stress and exhibit prolonged retention in mouse joints.

Biomaterials science (2020-07-01)
Kaamini M Dhanabalan, Vishal K Gupta, Rachit Agarwal
ABSTRACT

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 protected in vitro cartilage 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 ∼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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
C28/I2 Human Chondrocyte Cell Line, C28/I2 Human Chondrocyte Cell Line is widely used as a model cell line for studying normal and pathological cartilage repair mechanisms related to chondrocyte biology and physiology.
Sigma-Aldrich
Poly(vinyl alcohol), Mw 13,000-23,000, 87-89% hydrolyzed
Sigma-Aldrich
Resomer® RG 504 H, Poly(D,L-lactide-co-glycolide), acid terminated, lactide:glycolide 50:50, Mw 38,000-54,000
Sigma-Aldrich
Guanidine hydrochloride solution, 6M
Sigma-Aldrich
Fetal Bovine Serum, USA origin, sterile-filtered, suitable for cell culture, suitable for hybridoma
Sigma-Aldrich
Resomer® RG 653 H, Poly(D,L-lactide-co-glycolide), acid terminated, Mw 24,000-38,000
Sigma-Aldrich
Resomer® RG 503 H, Poly(D,L-lactide-co-glycolide), acid terminated, lactide:glycolide 50:50, Mw 24,000-38,000