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Enhanced Intradermal Delivery of Nanosuspensions of Antifilariasis Drugs Using Dissolving Microneedles: A Proof of Concept Study

Conventional oral administration of antifilariasis drugs results in nonspecific targeting of the drugs and the intradermal delivery of nanoparticles with sizes of <100 nm could be used to improve lymphatic uptake. This study investigated the combination of nanosuspension and dissolving microneedl...

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Autores principales: Permana, Andi Dian, McCrudden, Maelíosa T. C., Donnelly, Ryan F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6680801/
https://www.ncbi.nlm.nih.gov/pubmed/31319602
http://dx.doi.org/10.3390/pharmaceutics11070346
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author Permana, Andi Dian
McCrudden, Maelíosa T. C.
Donnelly, Ryan F.
author_facet Permana, Andi Dian
McCrudden, Maelíosa T. C.
Donnelly, Ryan F.
author_sort Permana, Andi Dian
collection PubMed
description Conventional oral administration of antifilariasis drugs results in nonspecific targeting of the drugs and the intradermal delivery of nanoparticles with sizes of <100 nm could be used to improve lymphatic uptake. This study investigated the combination of nanosuspension and dissolving microneedles (MN-NS) as an alternative intradermal delivery approach for the delivery of antifilariasis drugs, namely doxycycline, albendazole, and ivermectin. NS were fabricated and optimized using a bottom-up technique. The NS were then incorporated into the MN arrays. The optimized NS were <100 nm in diameter. Furthermore, MN-NS had suitable mechanical strength and insertion capabilities. The dermatokinetic study revealed that the delivery of drugs into the dermis of excised neonatal porcine skin by MNs was significantly higher than that from a needle-free patch, with 29.29 ± 4.65%, 31.54 ± 5.35%, and 34.54 ± 4.98% of doxycycline, albendazole sulfoxide, and ivermectin retained in the dermis after 24 h. The results presented here serve as proof of concept for the significant enhancement of drug retention times in the dermis, following their formulation into NS and delivery via MN. Leading on from these studies, future work must investigate in vivo lymphatic pharmacokinetic profiling of drugs formulated into NS, in a suitable animal model.
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spelling pubmed-66808012019-08-09 Enhanced Intradermal Delivery of Nanosuspensions of Antifilariasis Drugs Using Dissolving Microneedles: A Proof of Concept Study Permana, Andi Dian McCrudden, Maelíosa T. C. Donnelly, Ryan F. Pharmaceutics Article Conventional oral administration of antifilariasis drugs results in nonspecific targeting of the drugs and the intradermal delivery of nanoparticles with sizes of <100 nm could be used to improve lymphatic uptake. This study investigated the combination of nanosuspension and dissolving microneedles (MN-NS) as an alternative intradermal delivery approach for the delivery of antifilariasis drugs, namely doxycycline, albendazole, and ivermectin. NS were fabricated and optimized using a bottom-up technique. The NS were then incorporated into the MN arrays. The optimized NS were <100 nm in diameter. Furthermore, MN-NS had suitable mechanical strength and insertion capabilities. The dermatokinetic study revealed that the delivery of drugs into the dermis of excised neonatal porcine skin by MNs was significantly higher than that from a needle-free patch, with 29.29 ± 4.65%, 31.54 ± 5.35%, and 34.54 ± 4.98% of doxycycline, albendazole sulfoxide, and ivermectin retained in the dermis after 24 h. The results presented here serve as proof of concept for the significant enhancement of drug retention times in the dermis, following their formulation into NS and delivery via MN. Leading on from these studies, future work must investigate in vivo lymphatic pharmacokinetic profiling of drugs formulated into NS, in a suitable animal model. MDPI 2019-07-17 /pmc/articles/PMC6680801/ /pubmed/31319602 http://dx.doi.org/10.3390/pharmaceutics11070346 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Permana, Andi Dian
McCrudden, Maelíosa T. C.
Donnelly, Ryan F.
Enhanced Intradermal Delivery of Nanosuspensions of Antifilariasis Drugs Using Dissolving Microneedles: A Proof of Concept Study
title Enhanced Intradermal Delivery of Nanosuspensions of Antifilariasis Drugs Using Dissolving Microneedles: A Proof of Concept Study
title_full Enhanced Intradermal Delivery of Nanosuspensions of Antifilariasis Drugs Using Dissolving Microneedles: A Proof of Concept Study
title_fullStr Enhanced Intradermal Delivery of Nanosuspensions of Antifilariasis Drugs Using Dissolving Microneedles: A Proof of Concept Study
title_full_unstemmed Enhanced Intradermal Delivery of Nanosuspensions of Antifilariasis Drugs Using Dissolving Microneedles: A Proof of Concept Study
title_short Enhanced Intradermal Delivery of Nanosuspensions of Antifilariasis Drugs Using Dissolving Microneedles: A Proof of Concept Study
title_sort enhanced intradermal delivery of nanosuspensions of antifilariasis drugs using dissolving microneedles: a proof of concept study
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6680801/
https://www.ncbi.nlm.nih.gov/pubmed/31319602
http://dx.doi.org/10.3390/pharmaceutics11070346
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