Azelaic acid/β-cyclodextrin loaded hyaluronic acid-based dissolving microneedle for anti-acne application

Abstract

Azelaic acid (AZA) with superior safety and antibacterial resistance is considered one of the most promising active ingredients for the treatment of acne vulgaris. However, the poor water solubility, skin irritation, and low permeability seriously limit the commercial application of AZA. Herein, β-cyclodextrin (β-CD) was introduced to construct a supramolecular complex that solubilized AZA. Concurrently, the AZA/β-CD was encapsulated into hyaluronic acid (HA)-based dissolving microneedles (AZA/β-CD@HA MNs) to enhance the skin permeability and tolerability, particularly at larger doses. In vitro characterization, transdermal release, cytotoxicity detection, and antibacterial experiments revealed that the AZA/β-CD@HA MNs possess biocompatibility, biodegradability, and adequate mechanical strength to penetrate the stratum corneum barrier. Compared with commercial AZA gels, the AZA/β-CD@HA MNs exhibited superior transdermal delivery efficiency. Importantly, the MNs demonstrated strong antibacterial activity against Escherichia coli (E. coli) and Propionibacterium acnes (P. acnes). Meanwhile, it did not cause significant skin irritation, and the pinhole could heal quickly. The combination of supramolecular complex and HA-based dissolving MNs effectively addressed the shortcomings of AZA, making it promising for safer and more effective acne treatment.