Dissolvable microneedles loaded with denosumab alleviate knee osteoarthritis in rodent and canine models by inhibiting macrophage senescence.

ABSTRACT: Rationale: Osteoarthritis (OA) lacks disease-modifying therapies. Although systemic denosumab delays OA progression, it causes uneven drug distribution and off-target effects, whereas intra-articular injections are invasive and risk joint infection. We aimed to develop a minimally invasive microneedle platform that delivers denosumab locally to achieve therapeutic efficacy comparable to intra-articular injection while avoiding systemic exposure. Methods: A dissolvable denosumab-loaded microneedle array (MNs@De) was fabricated for transcutaneous intra-articular delivery. OA was induced in rodents and Beagle dogs; animals were treated with MNs@De, systemic denosumab, intra-articular denosumab, or vehicle. Synovial inflammation, cartilage erosion, and pain were evaluated histolo

SUBMITTER: Ming C 

PROVIDER: S-EPMC12665124 | biostudies-literature | 2026

REPOSITORIES: biostudies-literature