Melittin-Loaded Nanoparticle Microneedles Targeting M1 Macrophage for Arthritis Treatment

Arthritis is a joint inflammatory disease with multiple types that significantly compromises patients' quality of life. Current therapeutic efficiency is frequently constrained by the necessity for high dosages, the requirement for frequent administration, substantial side effects, and the risk of drug resistance. New therapeutic strategies are urgently needed. Melittin (Mel), a principal component of bee venom, has potent anti-inflammatory properties; however, its clinical application is limited by its hemolytic activity. To overcome the shortage, we developed targeted nanoparticles carrying Mel (MSC@NP-FA) with 68.3 ± 1.8% encapsulation efficiency, which were loaded within a microneedle (MN) to create MSC@NP-FA-MN. This strategy allows for precise anti-inflammatory therapy while reducing the risk of hemolysis. Both <i>in vitro</i> and <i>in vivo</i> studies demonstrated that MSC@NP-FA has lower hemolytic activity than Mel (<i>p</i> < 0.0001) and can target inflammatory macrophages to exert anti-inflammatory effects. <i>In vitro</i> transdermal test showed that more nanoparticles were delivered by the MNs (84.32 ± 6.97%) than bare nanoparticles (26.30 ± 2.55%) within 24 h. Furthermore, MSC@NP-FA-MN exhibited significant therapeutic efficacy without systemic toxicity or skin irritation in an adjuvant-induced arthritis (AIA) mouse model. Our findings highlight MSC@NP-FA-MN as a promising drug delivery system and suggest a new approach for safe and precise arthritis treatment.