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DNA vaccination for cervical cancer: Strategic optimisation of RALA mediated gene delivery from a biodegradable microneedle system
Ali, Ahlam A.
McCrudden, Cian M.
McBride, John W.
Kett, Vicky L.
Dunne, Nicholas J.
Donnelly, Ryan F.
McCarthy, Helen O.
Dissolvable 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.
DNA vaccine , Microneedle , RALA , Lyophilisation , Nanoparticle , Cervical Cancer
Cole, 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.2018.02.029