P134 - A magnesium ion sustained-releasing micro-sized PLGA capsule for the treatment of osteoarthritis
Abstract
Purpose
Osteoarthritis has become one of the most popular degenerative disease in the world. Based on the efficiency of magnesium ions (Mg2+) on the treatment of osteoarthritis, we developed a new drug sustained-releasing system which can be easily injected into articular cavity to sustainably release Mg2+ for treatment of OA.
Methods and Materials
PLGA was used to encapsule magnesium oxide (MgO) nanoparticles which were hydrophobicly modified and homo-dispersed by stearic acid. The most biocompatible ranges of concentration were achieved in PLGA-SS-MgO complex leaching solution in vitro. The fluidic complex was injected into rats’ knee joint cavity with osteoarthritis established by meniscus excision. Two and four weeks after surgery, rats knee joint were harvested and histologic sections were then staining by Safranin O/Fast Green and scored by OARSI standard. In vitro, we used cartilage from OA patients and IL-1β-incubated SW1353 cells (chondrosarcoma cells) to simulate the osteoarthritis environment. CCK8, Cell flow cytometry, Western Blot and q-PCR were performed for the exploration of possible mechanism.
Results
The most biocompatible Mg2+ concentrations is 10mM. MgO nanoparticles modified by stearic acid were encapsuled in PLGA microspheres. 2 and 4 weeks after injecting MgO&SS@PLGA into rats’ knee joint cavity, the tissue attrition of joint cartilage was significantly relieved (OARSI score 0.92±0.38 VS 2.75±0.69,2.67±0.61 VS 5.33± 0.41, P<0.0001). Also, subchondral bone were protected. In vitro experiments, Mg2+ increased the expression of SOX9 in nucleus and then activate phosphorylation of Akt through synthesis of p110α (one subunit of PI3K) in SW1353 cells. By activating the PI3K-Akt signal pathway, the apoptosis-specific protein Caspases was inhibited and the chondrocyte was protected from apoptosis.
Conclusion
In conclusion, 10mM Mg2+ are benefit to the treatment of osteoarthritis by anti-apoptosis of chondrocytes. Our preparation of a novel injectable and degradable MgO&SS@PLGA with Mg ions sustained releasing can be applied in clinical for OA treatment.
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