An Emulsion-Based Microneedle Formulation for Transdermal Delivery of Peptide Therapeutics

Polymeric microneedle patches represent a promising noninvasive platform for the transdermal delivery of peptide and protein therapeutics, and FDA-approved polymers are widely used for this purpose. However, maintaining peptide and protein stability during microneedle fabrication remains a significant challenge. Conventional strategies involve encapsulating within polymer nanoparticles/microparticles, or codissolving them with polymers in organic solvents before microneedle fabrication. These approaches are time-consuming and often lead to low loading efficiency and drug loss. In this study, we developed a novel direct emulsion-based encapsulation strategy that integrates peptides within the PLGA matrix during microneedle formation. This approach generates a uniform water-in-oil (W/O) emulsion that ensures homogeneous peptide dispersion while minimizing interfacial stress, eliminating the need for multistep spraying or postloading processes. The optimized PLGA-based microneedles exhibited uniform geometry, high drug-loading capacity, and strong mechanical integrity suitable for skin penetration. The encapsulated peptide maintains its biological activity after fabrication and during storage, confirming excellent peptide stability. In vivo studies demonstrated successful skin insertion and sustained peptide release for up to 72 h, supporting the potential of this platform for prolonged transdermal peptide delivery. Overall, this work presents a scalable, biocompatible, and solvent-safe microneedle fabrication strategy that preserves peptide functionality while enabling controlled drug release, making it a promising strategy for transdermal peptide therapeutics.