Preparation of combined colchicine with loxoprofen sodium loaded in dissolvable microneedles and its anti-gouty arthritis effect

Abstract

Both colchicine (Col) and loxoprofen sodium (LS) are first-line drugs for gouty arthritis (GA). Dissolvable microneedles (DMNs) represent an innovative transdermal drug delivery system (TDDS) that maximizes the therapeutic effect of drugs. In this paper, a novel TDDS of combined Col with LS loaded in DMNs (Col-LS-DMNS) was prepared to treat GA. To assess the synergistic effects of Col and LS, cell viability assays were conducted using monosodium urate (MSU)-induced HaCaT cells. The optimization of the Col-LS-DMNs formulation was carried out through sealing membrane puncture tests, single-factor experiments, and Box-Behnken response surface methodology. The quality of Col-LS-DMNs was assessed using high-performance liquid chromatography (HPLC), scanning electron microscopy (SEM), sealing membrane puncture tests, in vitro mouse skin puncture experiments, and Franz diffusion cell assays. The therapeutic effect of Col-LS DMNs on GA through animal experiments. Results demonstrated that Col and LS exhibit a synergistic effect, with optimal mass ratio of 1:1. The optimal formulation included PVP K30 and CMC Na at a mass ratio of 10:1, with 63% water content and a mixed dosage of Col and LS of 42 mg. The drug content in Col-LS-DMNs was (19.11±0.65) μg of Col and (20.69±0.89) μg of LS per tablet. SEM imaging revealed that the needle tips were conical. Additionally, Col-LS-DMNs exhibited favorable mechanical properties and caused minimal skin damage. After 24 hours, the cumulative permeation amount was (21.55±19.49) μg/cm2. Col-LS-DMNs significantly reduced MSU-induced ankle swelling and decreased serum concentrations of TNF-α, IL-6, and IL-1β in rats. In conclusion, Col-LS-DMNs represent a promising new treatment modality for GA.