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Spray-Formed Layered Polymer Microneedles for Controlled Biphasic Drug Delivery

In this study we present polymeric microneedles composed of multiple layers to control drug release kinetics. Layered microneedles were fabricated by spraying poly(lactic-co-glycolic acid) (PLGA) and polyvinylpyrrolidone (PVP) in sequence, and were characterized by mechanical testing and ex vivo ski...

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Autores principales: Park, Seok Chan, Kim, Min Jung, Baek, Seung-Ki, Park, Jung-Hwan, Choi, Seong-O
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6419157/
https://www.ncbi.nlm.nih.gov/pubmed/30960353
http://dx.doi.org/10.3390/polym11020369
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author Park, Seok Chan
Kim, Min Jung
Baek, Seung-Ki
Park, Jung-Hwan
Choi, Seong-O
author_facet Park, Seok Chan
Kim, Min Jung
Baek, Seung-Ki
Park, Jung-Hwan
Choi, Seong-O
author_sort Park, Seok Chan
collection PubMed
description In this study we present polymeric microneedles composed of multiple layers to control drug release kinetics. Layered microneedles were fabricated by spraying poly(lactic-co-glycolic acid) (PLGA) and polyvinylpyrrolidone (PVP) in sequence, and were characterized by mechanical testing and ex vivo skin insertion tests. The compression test demonstrated that no noticeable layer separation occurred, indicating good adhesion between PLGA and PVP layers. Histological examination confirmed that the microneedles were successfully inserted into the skin and indicated biphasic release of dyes incorporated within microneedle matrices. Structural changes of a model protein drug, bovine serum albumin (BSA), in PLGA and PVP matrices were examined by circular dichroism (CD) and fluorescence spectroscopy. The results showed that the tertiary structure of BSA was well maintained in both PLGA and PVP layers while the secondary structures were slightly changed during microneedle fabrication. In vitro release studies showed that over 60% of BSA in the PLGA layer was released within 1 h, followed by continuous slow release over the course of the experiments (7 days), while BSA in the PVP layer was completely released within 0.5 h. The initial burst of BSA from PLGA was further controlled by depositing a blank PLGA layer prior to forming the PLGA layer containing BSA. The blank PLGA layer acted as a diffusion barrier, resulting in a reduced initial burst. The formation of the PLGA diffusion barrier was visualized using confocal microscopy. Our results suggest that the spray-formed multilayer microneedles could be an attractive transdermal drug delivery system that is capable of modulating a drug release profile.
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spelling pubmed-64191572019-04-02 Spray-Formed Layered Polymer Microneedles for Controlled Biphasic Drug Delivery Park, Seok Chan Kim, Min Jung Baek, Seung-Ki Park, Jung-Hwan Choi, Seong-O Polymers (Basel) Article In this study we present polymeric microneedles composed of multiple layers to control drug release kinetics. Layered microneedles were fabricated by spraying poly(lactic-co-glycolic acid) (PLGA) and polyvinylpyrrolidone (PVP) in sequence, and were characterized by mechanical testing and ex vivo skin insertion tests. The compression test demonstrated that no noticeable layer separation occurred, indicating good adhesion between PLGA and PVP layers. Histological examination confirmed that the microneedles were successfully inserted into the skin and indicated biphasic release of dyes incorporated within microneedle matrices. Structural changes of a model protein drug, bovine serum albumin (BSA), in PLGA and PVP matrices were examined by circular dichroism (CD) and fluorescence spectroscopy. The results showed that the tertiary structure of BSA was well maintained in both PLGA and PVP layers while the secondary structures were slightly changed during microneedle fabrication. In vitro release studies showed that over 60% of BSA in the PLGA layer was released within 1 h, followed by continuous slow release over the course of the experiments (7 days), while BSA in the PVP layer was completely released within 0.5 h. The initial burst of BSA from PLGA was further controlled by depositing a blank PLGA layer prior to forming the PLGA layer containing BSA. The blank PLGA layer acted as a diffusion barrier, resulting in a reduced initial burst. The formation of the PLGA diffusion barrier was visualized using confocal microscopy. Our results suggest that the spray-formed multilayer microneedles could be an attractive transdermal drug delivery system that is capable of modulating a drug release profile. MDPI 2019-02-20 /pmc/articles/PMC6419157/ /pubmed/30960353 http://dx.doi.org/10.3390/polym11020369 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
Park, Seok Chan
Kim, Min Jung
Baek, Seung-Ki
Park, Jung-Hwan
Choi, Seong-O
Spray-Formed Layered Polymer Microneedles for Controlled Biphasic Drug Delivery
title Spray-Formed Layered Polymer Microneedles for Controlled Biphasic Drug Delivery
title_full Spray-Formed Layered Polymer Microneedles for Controlled Biphasic Drug Delivery
title_fullStr Spray-Formed Layered Polymer Microneedles for Controlled Biphasic Drug Delivery
title_full_unstemmed Spray-Formed Layered Polymer Microneedles for Controlled Biphasic Drug Delivery
title_short Spray-Formed Layered Polymer Microneedles for Controlled Biphasic Drug Delivery
title_sort spray-formed layered polymer microneedles for controlled biphasic drug delivery
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6419157/
https://www.ncbi.nlm.nih.gov/pubmed/30960353
http://dx.doi.org/10.3390/polym11020369
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