Design of a novel nano-lipoidal gel system for topical delivery of hydroxychloroquine in rheumatoid arthritis

Hydroxychloroquine (HCQ) is widely used in management of rheumatoid arthritis. However, its moderate bioavailability and serious systemic adverse effects limit its therapeutic utility for long term administration. A potential way to overcome these limitations is to develop topical dosage form of the drug, based on nanocarriers for better drug permeation. The nanoformulation was developed using biocompatible lipids and optimized using Box-Behnken experimental design. The optimized nanoformulation had a mean particle size of 110 nm, a polydispersity index of 0.11 and an entrapment efficiency of 84%. The formulation was further incorporated into a Carbopol 934 gel and evaluated for in vitro, ex vivo, and in vivo behaviour as well as therapeutic efficacy. Compared to the conventional gel, the nanogel formulation exhibited higher and sustained release of HCQ over a 24-hour period (67% vs 50%), penetrated the skin more readily (66%), and deposited more amount of drug in the deeper layers of skin. The formulation demonstrated significant anti-inflammatory activity, as measured by 76% inhibition of protein denaturation; in vivo efficacy (24% inhibition of paw edema) and good physicochemical for 6 months. Thus, HCQ nanogel formulation represents a promising transdermal drug delivery system for the better management of rheumatoid arthritis.