Preparation And Characterization Of KGN-PLGA Gel Composite Microspheres For Drug Delivery

Cartilage defect is caused by trauma, joint disease, aging and other factors, with continuing joint pain. Due to the lack of vessels and limited self-healing capacity in mature hyaline cartilage, aggravating cartilage damage affects the life quality of patients. The repair of articular cartilage defect is still a worldwide problem, tissue engineering provides a new way to repair cartilage defect by building a biomaterials-cell-growth factor system that presents enormous potential.A complex gel system was constructed for promoting repair articular cartilage. Hyaluronic acid(HA) is the main component of natural cartilage extracellular matrix, with a good biocompatibility and biodegradability. We modified HA by glycidyl methacrylate(MA) and obtained MA-HA which cross-linked under UV light. We prepared polylactic acid / polyglycolic acid copolymer(PLGA) microspheres encapsulated with small molecule drugs-Kartogenin(KGN), which were added into the MA-HA hydrogel to obtain a hydrogel composite material to achieve sustained release of KGN.We characterized gel systems using FESEM, Particle Size Analyzer to analyze microsphere surface morphology and particle size range respectively. NMR was utilized to analyze the composition of MA-HA. Then, we studied how the concentration of MA-HA and IRGACURE 2959 impact the mechanical and swelling properties of the gel. HPLC was used to study and analyze the drug release of KGN on a single microsphere delivery system and composite gel-microsphere drug delivery system. Finally, BMSCs was used to evaluate cell compatibility of gel system with a co-culture way in vitro.The PLGA microspheres fabricated by emulsion-solvent evaporation method exhibited a spherical morphology and the size was 700-900 nm using the optimized parameters, which can be well distributed in the HA hydrogel. NMR spectrum showed the characteristic peak of HA and MA, indicating the successful grafting reaction. Swelling behavior of the hydrogel was detected and the influence of the MA-HA or IRGACURE 2959 concentration was analyzed. The increase of MA-HA or IRGACURE 2959 concentration will reduce the swelling ratio within a certain range. On the other hand, the compressive modulus of the hydrogel increased with the higher MA-HA or IRGACURE 2959 concentration. Sustained release of KGN was studied and the cumulative release of the composite microspheres-hydrogel system was slower than the single microspheres system. The in vitro cell experiments demonstrated that, the prepared hydrogel can well support cell growth with high activities after 3 days culture. In addition, the effect of IRGACURE 2959 on the cell morphology and growth was also studied to confirm a safe concentration of IRGACURE 2959(<0.35 mg/?l). Therefore, the prepared composite hydrogel has potential application in cartilage repair.