Dissolving microneedles for DNA vaccination: Improving functionality via polymer characterization and RALA complexation
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 efficien...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2017-01-01
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| Series: | Human Vaccines & Immunotherapeutics |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/21645515.2016.1248008 |
| _version_ | 1827807721889464320 |
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| author | Grace Cole Joanne McCaffrey Ahlam A. Ali John W. McBride Cian M. McCrudden Eva M. Vincente-Perez Ryan F. Donnelly Helen O. McCarthy |
| author_facet | Grace Cole Joanne McCaffrey Ahlam A. Ali John W. McBride Cian M. McCrudden Eva M. Vincente-Perez Ryan F. Donnelly Helen O. McCarthy |
| author_sort | Grace Cole |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T22:01:29Z |
| format | Article |
| id | doaj.art-34001c2764484bf090f282e497651d6e |
| institution | Directory Open Access Journal |
| issn | 2164-5515 2164-554X |
| language | English |
| last_indexed | 2024-03-11T22:01:29Z |
| publishDate | 2017-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Human Vaccines & Immunotherapeutics |
| spelling | doaj.art-34001c2764484bf090f282e497651d6e2023-09-25T11:00:54ZengTaylor & Francis GroupHuman Vaccines & Immunotherapeutics2164-55152164-554X2017-01-01131506210.1080/21645515.2016.12480081248008Dissolving microneedles for DNA vaccination: Improving functionality via polymer characterization and RALA complexationGrace Cole0Joanne McCaffrey1Ahlam A. Ali2John W. McBride3Cian M. McCrudden4Eva M. Vincente-Perez5Ryan F. Donnelly6Helen O. McCarthy7School of Pharmacy, Queen's University BelfastSchool of Pharmacy, Queen's University BelfastSchool of Pharmacy, Queen's University BelfastSchool of Pharmacy, Queen's University BelfastSchool of Pharmacy, Queen's University BelfastSchool of Pharmacy, Queen's University BelfastSchool of Pharmacy, Queen's University BelfastSchool of Pharmacy, Queen's University BelfastDNA 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.http://dx.doi.org/10.1080/21645515.2016.1248008dna vaccinemicroneedlenanoparticlepvarala |
| spellingShingle | Grace Cole Joanne McCaffrey Ahlam A. Ali John W. McBride Cian M. McCrudden Eva M. Vincente-Perez Ryan F. Donnelly Helen O. McCarthy Dissolving microneedles for DNA vaccination: Improving functionality via polymer characterization and RALA complexation Human Vaccines & Immunotherapeutics dna vaccine microneedle nanoparticle pva rala |
| title | Dissolving microneedles for DNA vaccination: Improving functionality via polymer characterization and RALA complexation |
| title_full | Dissolving microneedles for DNA vaccination: Improving functionality via polymer characterization and RALA complexation |
| title_fullStr | Dissolving microneedles for DNA vaccination: Improving functionality via polymer characterization and RALA complexation |
| title_full_unstemmed | Dissolving microneedles for DNA vaccination: Improving functionality via polymer characterization and RALA complexation |
| title_short | Dissolving microneedles for DNA vaccination: Improving functionality via polymer characterization and RALA complexation |
| title_sort | dissolving microneedles for dna vaccination improving functionality via polymer characterization and rala complexation |
| topic | dna vaccine microneedle nanoparticle pva rala |
| url | http://dx.doi.org/10.1080/21645515.2016.1248008 |
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