TY - JOUR
T1 - A novel transdermal protein delivery strategy via electrohydrodynamic coating of PLGA microparticles onto microneedles
AU - Angkawinitwong, Ukrit
AU - Courtenay, Aaron J.
AU - Rodgers, Aoife
AU - Larraneta, Eneko
AU - Mccarthy, Helen O.
AU - Brocchini, Steve
AU - Donnelly, Ryan F.
AU - Williams, Gareth R.
N1 - Funding Information:
This work was supported in part by Wellcome Trust grant number WT094085MA. The authors gratefully acknowledge Dr Andrew Weston (UCL School of Pharmacy) for assistance with SEM and TEM measurements and John Frost (UCL School of Pharmacy) for his help with designing and manufacturing equipment for electrospraying.
Publisher Copyright:
Copyright © 2020 American Chemical Society.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/3/18
Y1 - 2020/3/18
N2 - 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.
AB - 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.
KW - PLGA
KW - electrohydrodynamic atomisation
KW - microneedle
KW - microparticles
KW - ovalbumin
KW - transdermal drug delivery
UR - https://pubs.acs.org/doi/10.1021/acsami.9b22425
UR - http://www.scopus.com/inward/record.url?scp=85082096890&partnerID=8YFLogxK
U2 - 10.1021/acsami.9b22425
DO - 10.1021/acsami.9b22425
M3 - Article
C2 - 32066234
VL - 12
SP - 12478
EP - 12488
JO - ACS Applied Materials and Interfaces
JF - ACS Applied Materials and Interfaces
SN - 1944-8244
IS - 11
ER -