Comprehensive chemical, morphological, thermal, and biological characterization of <i>Agave tequilana</i> extract and chitosan-based dissolving microneedle arrays

by Patricia Quintero-Rincón, Karina Caballero-Gallardo, Oscar Flórez-Acosta

Dissolving microneedles have gained attention as minimally invasive platforms for transdermal research applications. In this study, chitosan‑based dissolving microneedle arrays incorporating a hydroalcoholic extract of Agave tequilana root were formulated and systematically characterized. Chemical profiling by UHPLC-ESI-Orbitrap-MS revealed a diverse phytochemical composition dominated by phenolic acids, particularly rosmarinic acid. Morphological and structural analyses showed that extract incorporation induced concentration‑dependent changes in microneedle geometry: arrays containing 0.25% extract preserved tip sharpness, whereas a 0.50% loading led to surface roughening and partial tip deformation. Thermal analyses demonstrated extract‑dependent modifications in material degradation behavior, consistent with interactions between chitosan and extract constituents. Biological assays confirmed that the agave extract exhibits high antioxidant capacity, moderate tyrosinase inhibition, and inhibitory activity against collagenase and hyaluronidase. Following incorporation into the microneedle arrays, antioxidant activity and inhibitory effects against tyrosinase and hyaluronidase were retained, while collagenase inhibition was reduced, particularly in the 0.25% formulation. In vitro cytotoxicity assays indicated biocompatibility toward HaCaT keratinocytes and concentration-dependent selective cytotoxicity in A375 melanoma cells. Taken together, these findings indicate that extract loading is a critical parameter influencing structural preservation and in vitro bioactivity of chitosan‑based dissolving microneedles. Further studies addressing mechanical performance, insertion behavior, matrix dissolution, and skin permeation are required to evaluate the functional reliability of this system.