Preclinical development of a 3D-printed hollow microneedle platform for intradermal delivery of antioxidant-loaded nanocarriers.

The poor penetration of topical antioxidants underscores the need for advanced intradermal delivery platforms that overcome stratum corneum limitations while protecting labile compounds. Despite their efficacy, in-clinic treatments (microneedling, laser, injections) require frequent administration and entail high costs. Hollow microneedles (HMNs) provide a minimally invasive, precise, and versatile platform for intradermal drug delivery. Combined with nanotherapy approaches, they can protect labile compounds and enable localized release profiles. Here, we report the preclinical development of two designs of a 3D-printed HMN platform for intradermal delivery of resveratrol-loaded PLGA nanoparticles (RSV-NPs), as a proof-of-concept for antioxidant treatments. The HMNs fabricated by DLP 3D printing show precise geometry, favorable margin of safety, and enhanced RSV retention in the skin. An important advantage of this technology is the easy tunability of microneedle size, a critical parameter for depth-specific insertion and delivery control. Histological analysis confirms HMN (1 mm) reach the dermis, while HMN (1.5 mm) penetrate the dermis-hypodermis interface, enabling distinct delivery depths. RSV-NPs display optimal size, stability, high encapsulation efficiency, RSV photoprotection, sustained release, and controlled antioxidant activity with good biocompatibility. In vivo studies in human volunteers confirm the skin compatibility of the nanocarrier alone.