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.

Metal–Organic Frameworks (MOFs) and Their Composites as Emerging Biomaterials for Osteoarthritis Treatment

“…The composite was seeded with MC3T3-E1 cells, and morphological observation with SEM has shown that the composite was able to provide a favorable environment for cell proliferation. Results from the CCK-8 assay also confirmed the biocompatibility of the composite [ 40 ]. The study has demonstrated the potential of synergizing MOFs with hydrogels for more prolonged delivery of drugs or nutritional supplements while exerting anti-inflammatory effects at the target area.…”

“…Another factor affecting the stability of the composite, as reported, would be H 2 O 2 concentrations [ 43 ]. This will also be a variable in OA joints since H 2 O 2 is the precursor to a few other ROS [ 40 ]; hence, determining the degradation profile of composites under different H 2 O 2 concentrations could also be significant. Nonetheless, by having materials or other small molecules [ 54 ] in the MOF composites to endow them with sensitivity toward the external environment, the release rate of therapeutic molecules can hopefully be more patient-specific in future studies.…”

Current status and prospects of metal–organic frameworks for bone therapy and bone repair

“…Very recently, Yang et al prepared a gelatin–glucosamine hydrochloride/cross-linked-cyclodextrin metal–organic framework @IBU (G–GH/CL–CD–MOF@IBU) composite hydrogel. 58 It was prepared by soaking CL–CD–MOF in a highly concentrated solution of ibuprofen (IBU) and then mixing CL–CD–MOF@IBU uniformly into G–GH gel by an ultrasonic method. The three-dimensional network formed by this composite hydrogel prolonged the release time of the drug in the joint cavity, thus reducing the side effects caused by multiple injections.…”

Recent Advances in Metal–Organic-Framework-Based Nanocarriers for Controllable Drug Delivery and Release

“…Hence, CD MOF nanocarriers are favored for drug loading and release in the therapeutic field. Recently, more attention has been focused on the development of nanoscale CD MOFs for controlled drug delivery and release [130][131][132][133][134][135][136][137][138][139][140].…”