DNA vaccination for cervical cancer: Strategic optimisation of RALA mediated gene delivery from a biodegradable microneedle system

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dc.check.date2019-03-03
dc.check.infoAccess to this article is restricted until 12 months after publication by request of the publisher.en
dc.contributor.authorCole, Grace
dc.contributor.authorAli, Ahlam A.
dc.contributor.authorMcCrudden, Cian M.
dc.contributor.authorMcBride, John W.
dc.contributor.authorMcCaffrey, Joanne
dc.contributor.authorRobson, Tracey
dc.contributor.authorKett, Vicky L.
dc.contributor.authorDunne, Nicholas J.
dc.contributor.authorDonnelly, Ryan F.
dc.contributor.authorMcCarthy, Helen O.
dc.contributor.funderProstate Cancer UKen
dc.date.accessioned2018-03-22T13:00:33Z
dc.date.available2018-03-22T13:00:33Z
dc.date.issued2018-03-03
dc.description.abstractDissolvable microneedles can be employed to deliver DNA to antigen presenting cells within the skin. However, this technology faces two main challenges: the poor transfection efficacy of pDNA following release from the microneedle matrix, and the limited loading capacity of the micron-scale devices. Two-tier delivery systems combining microneedle platforms and DNA delivery vectors have increased efficacy but the challenge of increasing the loading capacity remains. This study utilised lyophilisation to increase the loading of RALA/pDNA nanoparticles within dissolvable PVA microneedles. As a result, delivery was significantly enhanced in vivo into an appropriate range for DNA vaccination (∼50 μg per array). Furthermore, modifying the manufacturing process was not detrimental to the microneedle mechanical properties or cargo functionality. It was demonstrated that arrays retained mechanical and functional stability over short term storage, and were able to elicit gene expression in vitro and in vivo. Finally, treatment with this novel formulation significantly retarded the growth of established tumours, and proved superior to standard intramuscular injection in a preclinical model of cervical cancer.en
dc.description.sponsorshipInvest Northern Ireland (Proof of Concept Grant (PoC330)); Prostate Cancer UK Award (S12-006)en
dc.description.statusPeer revieweden
dc.description.versionAccepted Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationCole, G., Ali, A. A., McCrudden, C. M., McBride, J. W., McCaffrey, J., Robson, T., Kett, V. L., Dunne, N. J., Donnelly, R. F. and McCarthy, H. O. (2018) 'DNA vaccination for cervical cancer: Strategic optimisation of RALA mediated gene delivery from a biodegradable microneedle system', European Journal of Pharmaceutics and Biopharmaceutics, 127, pp. 288-297. doi: 10.1016/j.ejpb.2018.02.029en
dc.identifier.doi10.1016/j.ejpb.2018.02.029
dc.identifier.endpage197en
dc.identifier.issn0939-6411
dc.identifier.journaltitleEuropean Journal of Pharmaceutics and Biopharmaceuticsen
dc.identifier.startpage288en
dc.identifier.urihttps://hdl.handle.net/10468/5684
dc.identifier.volume127en
dc.language.isoenen
dc.publisherElsevieren
dc.relation.urihttp://www.sciencedirect.com/science/article/pii/S0939641117313346
dc.rights© 2018 Published by Elsevier B.V. This manuscript version is made available under the CC-BY-NC-ND 4.0 license.en
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/en
dc.subjectDNA vaccineen
dc.subjectMicroneedleen
dc.subjectRALAen
dc.subjectLyophilisationen
dc.subjectNanoparticleen
dc.subjectCervical Canceren
dc.titleDNA vaccination for cervical cancer: Strategic optimisation of RALA mediated gene delivery from a biodegradable microneedle systemen
dc.typeArticle (peer-reviewed)en
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