Gelatin - glucosamine hydrochloride/crosslinked-Cyclodextrin Metal-organic frameworks @IBU composite hydrogel long-term sustained drug delivery system for osteoarthritis treatment

Abstract Osteoarthritis is a disease of articular cartilage degradation and inflammation of the joint capsule. Combining anti-inflammatory therapy with nutritional supplement is an effective means for the treatment of osteoarthritis. In this study, we prepared gelatin (Gel) - glucosamine hydrochloride (GH) mixed crosslinked-cyclodextrin metal-organic material (G-GH/CL-CD-MOF) composite hydrogel. Polyethylene glycol diglycidyl ether (PEGDE) was the crosslinking agent of GH and Gel to solve the problem of poor mechanical properties and water solubility at 37 ℃. CL-CD-MOF was fabricated through a simple one-step chemical reaction to crosslink the hydrophilic hydroxyl groups in CD-MOF with diphenyl carbonate (DPC). Electron microscopy and X-ray diffraction analysis of CL-CD-MOF showed perfect porous morphology with a chaotic internal structure. CL-CD-MOF@IBU was prepared by immersing CL-CD-MOF in high-concentration ibuprofen (IBU) solution. CL-CD-MOF@IBU was uniformly dispersed in Gel and GH mixed solution to prepare G-GH/CL-CD-MOF@IBU composite hydrogel long-term sustained drug delivery system. The compression curve of G-GH/CL-CD-MOF composite hydrogel showed a non-linear elastic behavior. The cyclic loading-unloading compression showed that the shape of the G-GH/CL-CD-MOF composite hydrogel can be kept intact under 50% strain. On the day 14, the G-GH/CL-CD-MOF@IBU composite hydrogel was degraded by 87.1%, 61% of IBU was released. G-GH/CL-CD-MOF@IBU exhibited good biocompatibility during co-culture with MC3T3-E1 cells. Briefly, the certain mechanical properties, sustained drug release behavior, and good biocompatibility of G-GH/CL-CD-MOF@IBU composite hydrogel showed that it has potential application in osteoarthritis treatment of long-term sustained nutritional supplement and anti-inflammatory synchronously.