Improved Transdermal Delivery of Rabies Vaccine using Iontophoresis Coupled Microneedle Approach
Aim This study was aimed to develop rabies vaccine incorporated microneedle (MN) patches and evaluate the immunogenicity of prepared formulations in combination with iontophoresis. Methods Patches comprising of polyvinyl pyrrolidone, hyaluronic acid and polyethylene glycol 400 were engineered by vacuum micromolding technique. Physical evaluation of patches included determination of folding endurance, % swelling and morphological features. In vitro release study was performed in skin simulant agarose gel using model drug (methylene blue) loaded patches. In vitro insertion ability was assessed using stratum corneum simulant parafilm. In vivo insertion study was performed in rats. Immunogenicity was evaluated in dogs by determining immunoglobulin G (IgG) and rabies virus neutralizing antibodies (RVNA) titer. Results Patches displayed uniformly distributed microprojections with pointed tips and smooth surface, ~ 70% swelling, remained intact for ~ 200 foldings and successfully penetrated the parafilm. The area covered by model drug across agarose gel was almost double following treatment with MN-iontophoresis combination ($ MN_{di} $) compared to MN alone ($ MN_{do} $). Histological examination of rat skin treated with vaccine laden MN ($ MN_{vo} $) and MN-iontophoresis combination ($ MN_{vi} $) confirmed the formation of grooves in epidermis without any damage to the deep vasculature. A ~ 73% and ~ 206% increase (compared to untreated counterpart) was observed in the IgG titer of $ MN_{vo} $ and $ MN_{vi} $ treated dogs, respectively. The RVNA titer was increased by ~ 1.2 and ~ 2.2 times (compared to threshold value) after $ MN_{vo} $ and $ MN_{vi} $ treatment, respectively. Conclusion MN-iontophoresis combination provided relatively potent immunogenic response over the conventional intramuscular injection, hence, can be used for administering vaccines transcutaneously. Graphical Abstract.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:40 |
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| Enthalten in: |
Pharmaceutical research - 40(2023), 8 vom: 25. Apr., Seite 2039-2049 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Arshad, Muhammad Sohail [VerfasserIn] |
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| Links: |
Volltext [lizenzpflichtig] |
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| Themen: |
Hyaluronic acid |
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| Anmerkungen: |
© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. |
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| doi: |
10.1007/s11095-023-03521-0 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
OLC2145167374 |
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| 245 | 1 | 0 | |a Improved Transdermal Delivery of Rabies Vaccine using Iontophoresis Coupled Microneedle Approach |
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| 520 | |a Aim This study was aimed to develop rabies vaccine incorporated microneedle (MN) patches and evaluate the immunogenicity of prepared formulations in combination with iontophoresis. Methods Patches comprising of polyvinyl pyrrolidone, hyaluronic acid and polyethylene glycol 400 were engineered by vacuum micromolding technique. Physical evaluation of patches included determination of folding endurance, % swelling and morphological features. In vitro release study was performed in skin simulant agarose gel using model drug (methylene blue) loaded patches. In vitro insertion ability was assessed using stratum corneum simulant parafilm. In vivo insertion study was performed in rats. Immunogenicity was evaluated in dogs by determining immunoglobulin G (IgG) and rabies virus neutralizing antibodies (RVNA) titer. Results Patches displayed uniformly distributed microprojections with pointed tips and smooth surface, ~ 70% swelling, remained intact for ~ 200 foldings and successfully penetrated the parafilm. The area covered by model drug across agarose gel was almost double following treatment with MN-iontophoresis combination ($ MN_{di} $) compared to MN alone ($ MN_{do} $). Histological examination of rat skin treated with vaccine laden MN ($ MN_{vo} $) and MN-iontophoresis combination ($ MN_{vi} $) confirmed the formation of grooves in epidermis without any damage to the deep vasculature. A ~ 73% and ~ 206% increase (compared to untreated counterpart) was observed in the IgG titer of $ MN_{vo} $ and $ MN_{vi} $ treated dogs, respectively. The RVNA titer was increased by ~ 1.2 and ~ 2.2 times (compared to threshold value) after $ MN_{vo} $ and $ MN_{vi} $ treatment, respectively. Conclusion MN-iontophoresis combination provided relatively potent immunogenic response over the conventional intramuscular injection, hence, can be used for administering vaccines transcutaneously. Graphical Abstract | ||
| 650 | 4 | |a hyaluronic acid | |
| 650 | 4 | |a iontophoresis | |
| 650 | 4 | |a microneedles | |
| 650 | 4 | |a polyvinyl pyrrolidone | |
| 650 | 4 | |a rabies vaccine | |
| 700 | 1 | |a Hussain, Saad |4 aut | |
| 700 | 1 | |a Zafar, Saman |4 aut | |
| 700 | 1 | |a Rana, Sadia Jafar |4 aut | |
| 700 | 1 | |a Ahmad, Nadia |4 aut | |
| 700 | 1 | |a Jalil, Najmusama Abdul |4 aut | |
| 700 | 1 | |a Ahmad, Zeeshan |4 aut | |
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