3D-Printed gelatin patches for topical delivery of niacinamide and vitamin A: Bridging microstructure, in vitro release, and in vivo penetration

Abstract

The development of advanced topical delivery systems that enhance skin penetration and ensure controlled release of bioactives is a key focus in pharmaceutical research. Semi-solid extrusion 3D printing (SSE-3DP) has emerged as a versatile technology for fabricating topical patches, allowing precise control over internal architecture to tailor release and penetration profiles.

This research investigates the integration of niacinamide (Nia) and vitamin A-palmitate (VitA) into printable gelatin-based inks, employing both pre-printing rheological assessments and post-printing structural analyses—scanning electron microscopy (SEM), micro-computed tomography (micro-CT) and mechanical properties (tension and compression).

Additionally, the study evaluates how variations in patch internal design affect the release kinetics and penetration profiles of Nia and VitA, utilizing both in vitro (Franz cells and Raman Microscopy, RM) and in vivo quantitative (Confocal Raman Spectroscopy, CRS) methodologies. Results indicated a significant correlation between in vitro and in vivo data. Additionally, RM provided valuable molecular-level insights, making it an effective in vitro tool for investigating skin retention.

CRS in vivo highlighted different penetration behaviors: while Nia penetration was strongly influenced by the patch design (porous vs. occlusive: 20 min, 0.074 ± 0.027 mg/cm² and 0.048 ± 0.022 mg/cm²; 40 min, 0.084 ± 0.037 mg/cm² and 0.052 ± 0.038 mg/cm²), particularly after short application times, VitA penetration was highly dependent on the integrity of the skin barrier (normal vs. slightly compromised).

Notably, this work introduced the first study to apply quantitative in vivo CRS to evaluate 3D-printed topical systems, highlighting the potential of SSE-3DP as a design-driven strategy for effective and personalized topical delivery.

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Bom, S., Prazeres, P., Pinto, P.C. et al. 3D-Printed gelatin patches for topical delivery of niacinamide and vitamin A: Bridging microstructure, in vitro release, and in vivo penetration. Drug Deliv. and Transl. Res. (2026). https://doi.org/10.1007/s13346-025-02031-3