Dosage-efficacy relationship and pharmacodynamics validation of brucine dissolving microneedles against rheumatoid arthritis

This study aims to define an optimal dosage and to investigate the therapeutic effects of brucine dissolving microneedles (Bru-DMNs) on rheumatoid arthritis (RA). Composite PVP K30 and CS were selected as needle tip materials, single PVA as a backing material, and brucine (Bru) as the drug of this model. Bru-DMNs were successfully fabricated by a two-step centrifugation method. The DMNs produced satisfactory mechanical strength and biocompatibility, and the needle body was completely dissolved in approximately 10 min. After microneedle (MN) administration, the skin recovered to its original state within 6 h free of irritation. The transdermal test in vitro revealed that the skin transmittance of Bru could be significantly improved by MN administration. Drug load in the MN was released after 6 h, with cumulative permeability at 94.84%. To define the optimal dosage of Bru-DMNs for RA, the present study established an RA rat model and administered different concentrations of Bru solution or suspension. The optimal dosage of MN production (approximately 124.50 g/patch) was determined when Bru concentration was at 16 mg/mL. Further pharmacodynamics exploration revealed that drug loading MN effectively inhibited toe swelling of RA rats, reduced synovial hyperplasia due to articular cartilage erosion, and diminished swelling in the thymus and spleen. Network pharmacological analysis demonstrated that Bru might play a role in the RA treatment by regulating TNF-ɑ, IL-17and IL-1β. This regulation pathway was verified by ELISA and western blot assays.