High-strength silk fibroin microneedles for transdermal colchicine delivery: a dose-response analysis demonstrating superior efficacy over oral administration

Oral colchicine remains a first-line therapy for acute gout arthritis. However, its clinical utility is limited by an extremely narrow therapeutic window and the frequent onset of dose-limiting gastrointestinal toxicity. To overcome these challenges, we developed high-strength silk fibroin separable microneedles (HSF SMNs) for transdermal colchicine delivery. The microneedles were fabricated from regenerated silk fibroin pre-modified with methanol vapor to enhance mechanical properties. Fourier-transform infrared spectroscopy and mechanical tests showed that treating the silk fibroin solution for 30 min induced substantial β-sheet formation, yielding HSF SMNs with a fracture force of 3.01 N per needle. In vitro permeation studies demonstrated that colchicine-loaded HSF SMNs exhibited a significantly higher transdermal flux compared to an aqueous solution. Notably, the system maintained 84.3% of its initial transdermal flux at 12 h after backing layer separation, indicating robust sustained-release capability. In a rat model of acute gouty arthritis, transdermal administration of HSF SMNs at low, medium, and high doses effectively suppressed paw swelling and reduced serum levels of IL-1β and TNF-α in an administered dose-dependent manner. Importantly, the therapeutic efficacy was superior to that achieved via oral gavage. To our knowledge, this work provides the first systematic dose-response analysis for transdermal colchicine delivered via microneedles, offering a promising non-oral alternative and supporting further development of this strategy. Graphic abstract The alternative text for this image may have been generated using AI.