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

Abstract

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/m²·h after the application of DMNs and returned to normal levels (12.25 ± 0.21 g/m²·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.

Keywords:

• Transdermal drug delivery
• dissolving microneedles
• allopurinol
• hyperuricemia
• gout

Acknowledgements

Ethics statement: No human subjects were used for studies that are the basis of this research. All experimental procedures involving animals were performed in accordance with protocols approved by the Putian University Animal Use and Care Committee (Protocol #2020(30)).

Disclosure statement

The authors confirm that this article content has no conflict of interest.

Additional information

Funding

This work was supported by National Natural Science Foundation of China (Grant No. 82001926), the Natural Science Foundation of Fujian Province (Grant No. 2019J01806), the Putian Science and Technology Bureau (Grant No. 2018SP3004), and Training Program of Innovation and Entrepreneurship for Undergraduates (Grant Nos. S202011498003, S202011498004, and S202011498034).