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Needleless administration of advanced therapies into the skin via the appendages using a hypobaric patch

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Faiza Benaouda, Ricardo Inacio, Chui Hua Lim, Haeeun Park, Thomas Pitcher, Mohamed A. Alhnan, Mazen M. S. Aly, Khuloud T Al-jamal, Ka-Lung Chan, Rikhav P. Gala, Daniel Sebastia-saez, Liang Cui, Tao Chen, Julie Keeble, Stuart A. Jones

Original languageEnglish
Article numbere2120340119
Pages (from-to)e2120340119
JournalProceedings of the National Academy of Sciences of the United States of America
Volume119
Issue number18
DOIs
Accepted/In press16 Mar 2022
Published3 May 2022

Bibliographical note

Funding Information: ACKNOWLEDGMENTS. Funding for this study was provided for R.I. by a Biotechnology and Biological Sciences Research Council PhD CASE studentship. F.B. and S.A.J. were funded by Engineering and Physical Sciences Research Council (EPSRC) Grant EP/S021167/1 and a grant from the RoseTree’s Trust with the Sto-nyGate Trust. Funding for D.S.-S. was provided by EPSRC Grant Number EP/ S021159/1. Publisher Copyright: © 2022 National Academy of Sciences. All rights reserved.

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Abstract

Advanced therapies are commonly administered via injection even when they act within the skin tissue, and this increases the chances of off-target effects. Here we report the use of a skin patch containing a hypobaric chamber that induces skin dome formation to enable needleless delivery of advanced therapies directly into porcine, rat, and mouse skin. Finite element method modeling showed that the hypobaric chamber in the patch opened the skin appendages by 32%, thinned the skin, and compressed the appendage wall epithelia. These changes allowed direct delivery of an H1N1 vaccine antigen and a diclofenac nanotherapeutic into the skin. Fluorescence imaging and infrared mapping of the skin showed needleless delivery via the appendages. The in vivo utility of the patch was demonstrated by a superior immunoglobulin G response to the vaccine antigen in mice compared to intramuscular injection and a 70% reduction in rat paw swelling in vivo over 5 h with diclofenac without skin histology changes.

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