title: Dissolving microneedles for DNA vaccination: Improving functionality via polymer characterization and RALA complexation.
abstract: DNA vaccination holds the potential to treat or prevent nearly any immunogenic disease, including cancer. To date, these vaccines have demonstrated limited immunogenicity in vivo due to the absence of a suitable delivery system which can protect DNA from degradation and improve transfection efficiencies in vivo. Recently, microneedles have been described as a novel physical delivery technology to enhance DNA vaccine immunogenicity. Of these devices, dissolvable microneedles promise a safe, pain-free delivery system which may simultaneously improve DNA stability within a solid matrix and increase DNA delivery compared to solid arrays. However, to date little work has directly compared the suitability of different dissolvable matrices for formulation of DNA-loaded microneedles. Therefore, the current study examined the ability of 4 polymers to formulate mechanically robust, functional DNA loaded dissolvable microneedles. Additionally, complexation of DNA to a cationic delivery peptide, RALA, prior to incorporation into the dissolvable matrix was explored as a means to improve transfection efficacies following release from the polymer matrix. Our data demonstrates that DNA is degraded following incorporation into PVP, but not PVA matrices. The complexation of DNA to RALA prior to incorporation into polymers resulted in higher recovery from dissolvable matrices, and increased transfection efficiencies in vitro. Additionally, RALA/DNA nanoparticles released from dissolvable PVA matrices demonstrated up to 10-fold higher transfection efficiencies than the corresponding complexes released from PVP matrices, indicating that PVA is a superior polymer for this microneedle application.
authors.affiliation: a School of Pharmacy, Queen's University Belfast , Belfast , Northern Ireland , UK.
authors.forename: Grace
authors.initials: G
authors.lastname: Cole
authors.affiliation: a School of Pharmacy, Queen's University Belfast , Belfast , Northern Ireland , UK.
authors.forename: Joanne
authors.initials: J
authors.lastname: McCaffrey
authors.affiliation: a School of Pharmacy, Queen's University Belfast , Belfast , Northern Ireland , UK.
authors.forename: Ahlam A
authors.initials: AA
authors.lastname: Ali
authors.affiliation: a School of Pharmacy, Queen's University Belfast , Belfast , Northern Ireland , UK.
authors.forename: John W
authors.initials: JW
authors.lastname: McBride
authors.affiliation: a School of Pharmacy, Queen's University Belfast , Belfast , Northern Ireland , UK.
authors.forename: Cian M
authors.initials: CM
authors.lastname: McCrudden
authors.affiliation: a School of Pharmacy, Queen's University Belfast , Belfast , Northern Ireland , UK.
authors.forename: Eva M
authors.initials: EM
authors.lastname: Vincente-Perez
authors.affiliation: a School of Pharmacy, Queen's University Belfast , Belfast , Northern Ireland , UK.
authors.forename: Ryan F
authors.initials: RF
authors.lastname: Donnelly
authors.affiliation: a School of Pharmacy, Queen's University Belfast , Belfast , Northern Ireland , UK.
authors.forename: Helen O
authors.initials: HO
authors.lastname: McCarthy
mesh_terms: D000818:Animals; D004337:Drug Carriers; D016503:Drug Delivery Systems / Q000295:instrumentation*; D008297:Male; D008810:Mice, Inbred C57BL; D009339:Needles; D011108:Polymers; D014611:Vaccination / Q000295:instrumentation*; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000493:pharmacokinetics
chemical_list: D004337:Drug Carriers; D011108:Polymers; D019444:Vaccines, DNA
keywords: DNA vaccine; PVA; RALA; microneedle; nanoparticle