title: Transcending epithelial and intracellular biological barriers; a prototype DNA delivery device.
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.
authors.affiliation: School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast BT9 7BL, Northern Ireland, UK.
authors.forename: Joanne
authors.initials: J
authors.lastname: McCaffrey
authors.affiliation: School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast BT9 7BL, Northern Ireland, UK.
authors.forename: Cian M
authors.initials: CM
authors.lastname: McCrudden
authors.affiliation: School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast BT9 7BL, Northern Ireland, UK.
authors.forename: Ahlam A
authors.initials: AA
authors.lastname: Ali
authors.affiliation: School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast BT9 7BL, Northern Ireland, UK.
authors.forename: Ashley S
authors.initials: AS
authors.lastname: Massey
authors.affiliation: School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast BT9 7BL, Northern Ireland, UK.
authors.forename: John W
authors.initials: JW
authors.lastname: McBride
authors.affiliation: School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast BT9 7BL, Northern Ireland, UK.
authors.forename: Maelíosa T C
authors.initials: MT
authors.lastname: McCrudden
authors.affiliation: School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast BT9 7BL, Northern Ireland, UK.
authors.forename: Eva M
authors.initials: EM
authors.lastname: Vicente-Perez
authors.affiliation: School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast BT9 7BL, Northern Ireland, UK.
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Coulter
authors.affiliation: School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast BT9 7BL, Northern Ireland, UK.
authors.forename: Tracy
authors.initials: T
authors.lastname: Robson
authors.affiliation: School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast BT9 7BL, Northern Ireland, UK.
authors.forename: Ryan F
authors.initials: RF
authors.lastname: Donnelly
authors.affiliation: School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast BT9 7BL, Northern Ireland, UK. Electronic address: h.mccarthy@qub.ac.uk.
authors.forename: Helen O
authors.initials: HO
authors.lastname: McCarthy
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D002460:Cell Line; D057846:Cell-Penetrating Peptides / Q000737:chemistry* / Q000378:metabolism; D004247:DNA / Q000008:administration & dosage* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D018014:Gene Transfer Techniques / Q000295:instrumentation*; D006801:Humans; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000737:chemistry* / Q000378:metabolism; D009339:Needles; D010957:Plasmids / Q000008:administration & dosage* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011205:Povidone / Q000737:chemistry / Q000378:metabolism; D012867:Skin / Q000378:metabolism; D013552:Swine
chemical_list: D057846:Cell-Penetrating Peptides; D004247:DNA; D011205:Povidone
keywords: Cell penetrating peptide; DNA nanoparticle; Gene delivery; Gene therapy; Microneedle