A Novel Transdermal Protein Delivery Strategy via Electrohydrodynamic Coating of PLGA Microparticles onto Microneedles

• DOI: 10.1021/acsami.9b22425
• Publication Date: 2020-02-18T09:49:25Z
• Authors: Ukrit Angkawinitwong; Aaron J. Courtenay; Aoife M. Rodgers; Eneko Larrañeta; Helen O. McCarthy; Steve Brocchini; Ryan F. Donnelly; Gareth R. Williams
• Keywords: 570; Microinjections; Ovalbumin; 610; Dendritic Cells; Electrochemical Techniques; 02 engineering and technology; Administration, Cutaneous; Mice, Inbred C57BL; Mice; Coated Materials, Biocompatible; Polylactic Acid-Polyglycolic Acid Copolymer; Needles; Animals; Humans; Nanoparticles; Female; 0210 nano-technology; Cells, Cultured

Transdermal delivery of biological therapeutics is emerging as a potent alternative to intravenous or subcutaneous injections. The latter possess major challenges including patient discomfort, the necessity for trained personnel, specialized sharps disposal, and risk of infection. The microneedle (MN) technology circumvents many of the abovementioned challenges, delivering biological materials directly into the skin and allowing sustained release of the active ingredient both in animal models and in humans. This study describes the use of electrohydrodynamic atomization (EHDA) to coat ovalbumin (OVA)-loaded PLGA nanoparticles onto hydrogel-forming MN arrays. The particles showed extended release of OVA over ca. 28 days. Microscopic analysis demonstrated that EHDA could generate a uniform particle coating on the MNs, with 30% coating efficiency. Furthermore, the coated MN array manifested similar mechanical characteristics and insertion properties to the uncoated system, suggesting that the coating should have no detrimental effects on the application of the MNs. The coated MNs resulted in no significant increase in anti-OVA-specific IgG titres in C57BL/6 mice in vivo as compared to the untreated mice (paired t-test, p > 0.05), indicating that the formulations are nonimmunogenic. The approach of using EHDA to coat an MN array thus appears to have potential as a novel noninvasive protein delivery strategy.