Cartilage-targeting Poly(Ethyleneglycol) (PEG)-formononetin (FMN) Nanodrug for Treating Osteoarthritis

Abstract

Intra-articular (IA) injection is an efficient treatment for osteoarthritis. Such a treatment will minimize systemic side effects and avoid the inconvenience of frequent injections. However, the joint has poor bioavailability for systemically administered drugs and experiences rapid clearance of therapeutics after intra-articular injection. Delivering system modified through active targeting strategies to facilitate localization within specific joint tissues such as cartilage is hopeful to increase the therapeutic effects. In this study, we designed a nanoscaled amphiphilic and cartilage-targeting polymer-drug delivery system by using formononetin (FMN)-poly(ethylene glycol) (PEG) (denoted as PCFMN), which was prepared by PEGylation of FMN followed by coupling with cartilage-targeting peptide (CollBP). Our results showed that PCFMN was approximately regular spherical with the average diameter about 218 nm. The in vitro test using IL-1β stimulated chondrocytes indicated that PCFMN were biocompatible and upregulated anabolic genes while simultaneously downregulated catabolic genes of the articular cartilage. The therapeutic effects in vivo indicated that PCFMN could effectively attenuate the progression of OA as evidenced by immunohistochemical staining and histological analysis. In addition, PCFMN showed higher intention time in joints and better anti-inflammatory effects than FMN, indicating the efficacy of cartilage targeting nanodrug on OA. This study may provide reference for clinical OA therapy.