ORCID

0009-0008-6637-5290 (Peet), 0000-0002-3837-1777 (Agrahari), 0009-0007-9374-6248 (Ouattara), 0009-0009-9641-1325 (Doncel)

Document Type

Article

Publication Date

2026

DOI

10.1021/acs.molpharmaceut.5c01650

Publication Title

Molecular Pharmaceutics

Volume

23

Issue

8

Pages

4048-4057

Abstract

Broadly neutralizing antibodies (bnAbs) are advancing as a preventative or treatment option for HIV infection, but currently must be administered parenterally, typically as a large injection or infusion, an invasive method of delivery, especially for the pediatric population. Here, we present proof-of-concept data on a minimally invasive microneedle (MN) patch platform codelivering three bnAbs, PGT121, VRC07-523LS, and PGDM1400LS, from separate MN patch units or pixels. Each 1 cm² patch pixel, fabricated via solvent casting, contained ∼2 mg of one bnAb. In ex vivo porcine skin tests, the MNs effectively penetrated the skin. When tested in vitro in PBS buffer, MNs quickly dissolved, fully releasing bnAbs within 10 min. VRC07-523LS and PGT121 functionality was maintained during patch manufacturing, as confirmed by an in vitro HIV-1 neutralization assay, while PGDM1400LS lost some potency. In a rat model, coadministration of 1 cm² patch units for each bnAb resulted in systemic exposure by the first collection time point of 3 h, reaching maximal concentrations by day 3 of up to 68 μg/mL. These preliminary findings suggest that the MN patch platform may serve as a promising alternative to injectable bnAb formulations for HIV prevention and treatment, particularly in neonates and infants, although further investigation is required to establish its clinical utility. Additionally, the solid-state MN formulation of bnAbs may eliminate the need for cold-chain storage or distribution, making the patch particularly suitable for use in resource-limited settings.

Rights

© 2026 The Authors.

This publication is licensed under a Creative Commons Attribution 4.0 International (CC BY 4.0) License.

Original Publication Citation

Peet, M. M., Agrahari, V., Singh, P., Nguyen, L. L. H., Ouattara, L. A., Yang, E. S., Herrera, C., Pegu, A., Pierson, T. C., Nguyen, T. D., & Doncel, G. F. (2026). Proof-of-concept development and preclinical evaluation of a microarray patch platform for codelivery of multiple broadly neutralizing antibodies for HIV prevention. Molecular Pharmaceutics, 23(8), 4048-4057. https://doi.org/10.1021/acs.molpharmaceut.5c01650

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