Transcending epithelial and intracellular biological barriers; a prototype DNA delivery device

Joanne McCaffrey, Cian M McCrudden, Ahlam A Ali, Ashley S Massey, John W McBride, Maelíosa T C McCrudden, Eva M Vicente-Perez, Jonathan A Coulter, Tracy Robson, Ryan F Donnelly, Helen O McCarthy

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Microneedle technology provides the opportunity for the delivery of DNA therapeutics by a non-invasive, patient acceptable route. To deliver DNA successfully requires consideration of both extra and intracellular biological barriers. In this study we present a novel two tier platform; i) a peptide delivery system, termed RALA, that is able to wrap the DNA into nanoparticles, protect the DNA from degradation, enter cells, disrupt endosomes and deliver the DNA to the nucleus of cells ii) a microneedle (MN) patch that will house the nanoparticles within the polymer matrix, breach the skin's stratum corneum barrier and dissolve upon contact with skin interstitial fluid thus releasing the nanoparticles into the skin. Our data demonstrates that the RALA is essential for preventing DNA degradation within the poly(vinylpyrrolidone) (PVP) polymer matrix. In fact the RALA/DNA nanoparticles (NPs) retained functionality when in the MN arrays after 28days and over a range of temperatures. Furthermore the physical strength and structure of the MNs was not compromised when loaded with the NPs. Finally we demonstrated the effectiveness of our MN-NP platform in vitro and in vivo, with systemic gene expression in highly vascularised regions. Taken together this 'smart-system' technology could be applied to a wide range of genetic therapies.

Original languageEnglish
Pages (from-to)238-47
Number of pages10
JournalJournal of controlled release : official journal of the Controlled Release Society
Volume226
Early online date13 Feb 2016
DOIs
Publication statusPublished - 28 Mar 2016

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