Alginate-hydrogel forming microneedle arrays for enhanced skin local delivery of resveratrol: overcoming bioavailability barriers.

Resveratrol (RSV), a natural polyphenol from stilbenoids group, has gained significant interest for its numerous diverse therapeutic effects, including anti-ageing properties. Despite its potential, the bioavailability and solubility of RSV are suboptimal for topical skin administration. To overcome this, polymeric microneedles (MNs), composed of alginate alone or blended with k-carrageenan (k-CRG), were developed. In the present study, an optimized micromoulding technique was established to produce 400 μm-long arrays. Rhodamine B (RB) was employed as a model compound for the fabrication, characterization, and selection of the most promising platform for localized dermal delivery. RB-loaded alginate-hydrogel forming MNs exhibited high skin retention (≈75% of the applied dose; ≈0.06 mg) with minimal permeation over 24 h, whereas an RB solution resulted in higher permeation and lower apical retention. RSV-loaded MNs were subsequently fabricated and structurally characterized, demonstrating appropriate geometry and mechanical strength for skin penetration. Alginate-hydrogel MNs displayed a compression force of 0.89 N, which increased to 2.37 N upon RSV loading, confirming their robustness for reliable skin insertion. RSV-loaded alginate-hydrogel forming MNs reduced apparent permeability from 3 × 10−7 cm s−1 (solution) to 6 × 10−9 cm s−1 and decreased 24 h permeation by approximately 4-fold, while retaining ≈2% of the initial RSV dose (≈24 μg) within the skin. Cytocompatibility assays confirmed that the formulation did not impair human keratinocyte viability at RSV concentrations up to 0.05% (w/v). Overall, these experimental data indicate that alginate-based MNs are a promising platform for the topical administration of RSV in anti-ageing applications.