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.