Electrosprayed PLA/Spirulina Hybrid Microparticles for Enhanced Dermal Delivery on HUVEC and HaCaT Cell Lines of Niacinamide and Palmitoyl‐Tripeptide‐1

ABSTRACT Developing advanced delivery systems for dermal applications requires innovative approaches to overcome compound solubility, stability, and cellular uptake limitations. This study develops electrosprayed poly(lactic acid)/Spirulina (PLA/Spi) hybrid microparticles for efficient dermal delivery of hydrophilic (niacinamide) and lipophilic (palmitoyl‐tripeptide‐1) compounds. The optimized microparticles demonstrated remarkable dose‐sparing effects, achieving comparable bioactivity at reduced concentrations versus free compounds. Cellular uptake peaked at 5 µg/mL in endothelial cells (HUVEC, 44.5%) and keratinocytes (35.6%), showing an inverse concentration–uptake relationship linked to improved particle dispersion. The system maintained excellent biocompatibility while exhibiting cell‐specific responses: enhanced endothelial proliferation with encapsulated palmitoyl‐tripeptide‐1 and improved keratinocyte migration with niacinamide. Notably, the Spirulina carrier displayed intrinsic wound‐healing activity. These findings highlight the platform's potential for dermatological applications, offering simultaneous delivery of diverse bioactives with dramatically reduced dosage requirements. The observed particle–cell interactions suggest novel mechanisms for optimizing delivery efficiency, warranting further investigation of underlying cellular processing pathways. This technology shows promise for wound healing, photoprotection, and targeted dermal therapies.