Cyclodextrin-based supramolecular dissolving microneedles for enhanced transdermal delivery of azelaic acid in acne vulgaris treatment

Acne vulgaris is a common skin condition affecting individuals of various age groups, significantly impacting their quality of life. Although azelaic acid (AZA) is widely used in acne treatment due to its anti-inflammatory, antibacterial, and tyrosinase inhibitory properties, its low aqueous solubility limits its transdermal absorption and reduces therapeutic efficacy. Dissolving microneedles (DMNs), fabricated from water-soluble materials, have shown great potential as a strategy for improving transdermal drug delivery. However, DMNs face challenges in encapsulating poorly soluble drugs like AZA. In this study, we developed cyclodextrin-based supramolecular DMNs loaded with AZA, in which the microneedles are composed entirely of inclusion complexes to enhance the transdermal delivery efficiency of AZA for treating acne. AZA was encapsulated into hydroxypropyl-β-cyclodextrin (HP-β-CD) and sulfobutylether-β-cyclodextrin (SBE-β-CD) using a solvent evaporation technique, resulting in respective 34.9-fold and 25.4-fold increases in AZA solubility. The inclusion complexes demonstrated superior antibacterial activity in inhibition zone assays and enhanced tyrosinase inhibitory activity compared to free AZA in aqueous solution, suggesting enhanced dispersion and biological activity. The DMNs exhibited excellent mechanical strength and maintained a high drug-loading capacity of AZA, facilitating efficient penetration through the stratum corneum. In vitro permeation test showed 24-h percutaneous permeability rates at 68.69 ± 3.79 % and 73.59 ± 4.23 % for AZA/HP-β-CD DMNs and AZA/SBE-β-CD DMNs, respectively. Additionally, the DMNs demonstrated no cytotoxicity toward L929 cells and displayed hemocompatibility. Overall, the developed supramolecular DMNs system presents a promising approach for enhancing the transdermal delivery of AZA, with the potential to enhance therapeutic outcomes in acne treatment.