Use of mesoporous polydopamine nanoparticles as a stable drug-release system alleviates inflammation in knee osteoarthritis

Osteoarthritis drugs are often short-acting; therefore, to enhance their efficacy, long-term, stable-release, drug-delivery systems are urgently needed. Mesoporous polydopamine (MPDA), a natural nanoparticle with excellent biocompatibility and a high loading capacity, synthesized via a self-aggregation-based method, is frequently used in tumor photothermal therapy. Here, we evaluated its efficiency as a sustained and controlled-release drug carrier and investigated its effectiveness in retarding drug clearance. To this end, we used MPDA as a controlled-release vector to design a drug-loaded microsphere system (RCGD423@MPDA) for osteoarthritis treatment, and thereafter, tested the efficacy of the system in a rat model of osteoarthritis. The results indicated that at an intermediate drug-loading dose, MPDA showed high drug retention. Furthermore, the microsphere system maintained controlled drug release for over 28 days. Our in vitro experiments also showed that drug delivery using this microsphere system inhibited apoptosis-related cartilage degeneration, whereas MPDA-only administration did not show obvious cartilage degradation improvement effect. Results from an in vivo osteoarthritis model also confirmed that drug delivery via this microsphere system inhibited cartilage damage and proteoglycan loss more effectively than the non-vectored drug treatment. These findings suggest that MPDA may be effective as a controlled-release carrier for inhibiting the overall progression of osteoarthritis. Moreover, they provide insights into the selection of drug-clearance retarding vectors, highlighting the applicability of MPDA in this regard.