Fabrication and characterization of dissolving microneedles for transdermal drug delivery of allopurinol

Allopurinol (AP) is the first line drug in treating hyperuricemia and gout in clinical by oral drug delivery, which is associated with severe adverse effects and the hepatic first-pass effect. Herein, we first proposed AP encapsulated dissolving microneedles (DMNs) for transdermal drug delivery to realize the sustained drug release and avoid the hepatic first-pass effect, which will help to reduce the adverse effects and improve the bioavailability of AP. DMNs were fabricated by a suspension solution casting method with precisely controlled dose. They had sufficient mechanical strength to penetrate through the skin and resulted in the formation of hundreds of micropores in skin. The results of in vitro and ex vivo release experiments demonstrated that the release profile of DMNs was independent with the dose of AP, and they indeed had much higher drug delivery efficiency (DDE) than the equal amount of AP in solutions. In vivo DDE reached to 38.9% within 1 h, and the drug residual can be served as a drug reservoir for sustained drug release. The result of pharmacodynamic study further confirmed that the sustained release and the anti-hyperuricemia effect of DMNs encapsulating AP were achieved. Moreover, transepidermal water loss significantly increased to 49.50 +/- 3.82 g/m(2)center dot h after the application of DMNs and returned to normal levels (12.25 +/- 0.21 g/m(2)center dot h) after 8 h, indicating that the DMNs were well tolerated. These results suggest that transdermal drug delivery of AP by using DMNs is an efficient and safe alternative to currently available routes of administration.