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Rapidly dissolving polymeric microneedles for minimally invasive intraocular drug delivery
In this study, dissolving microneedles (MNs) were used to enhance ocular drug delivery of macromolecules. MNs were fabricated using polyvinylpyrrolidone (PVP) polymer of various molecular weights (MWs) containing three model molecules of increasing MW, namely fluorescein sodium and fluorescein isoth...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer US
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5097091/ https://www.ncbi.nlm.nih.gov/pubmed/27709355 http://dx.doi.org/10.1007/s13346-016-0332-9 |
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author | Thakur, Raghu Raj Singh Tekko, Ismaiel A. Al-Shammari, Farhan Ali, Ahlam A. McCarthy, Helen Donnelly, Ryan F. |
author_facet | Thakur, Raghu Raj Singh Tekko, Ismaiel A. Al-Shammari, Farhan Ali, Ahlam A. McCarthy, Helen Donnelly, Ryan F. |
author_sort | Thakur, Raghu Raj Singh |
collection | PubMed |
description | In this study, dissolving microneedles (MNs) were used to enhance ocular drug delivery of macromolecules. MNs were fabricated using polyvinylpyrrolidone (PVP) polymer of various molecular weights (MWs) containing three model molecules of increasing MW, namely fluorescein sodium and fluorescein isothiocyanate–dextrans (with MW of 70 k and 150 k Da). Arrays (3 × 3) of PVP MNs with conical shape measuring about 800 μm in height with a 300 μm base diameter, containing the model drugs, were fabricated and characterized for their fracture forces, insertion forces (in the sclera and cornea), depth of penetration (using OCT and confocal imaging), dissolution time and in vitro permeation. The average drug content of the MNs (only in MN shafts) ranged from 0.96 to 9.91 μg, and the average moisture content was below 11 %. High MW PVP produced MNs that can withstand higher forces with minimal reduction in needle height. PVP MNs showed rapid dissolution that ranged from 10 to 180 s, which was dependent upon PVP’s MW. In vitro studies showed significant enhancement of macromolecule permeation when MNs were used, across both the corneal and scleral tissues, in comparison to topically applied aqueous solutions. Confocal images showed that the macromolecules formed depots within the tissues, which led to sustained permeation. However, use of MNs did not significantly benefit the permeation of small molecules; nevertheless, MN application has the potential for drug retention within the selected ocular tissues unlike topical application for small molecules. The material used in the fabrication of the MNs was found to be biocompatible with retinal cells (i.e. ARPE-19). Overall, this study reported the design and fabrication of minimally invasive rapidly dissolving polymeric MN arrays which were able to deliver high MW molecules to the eye via the intrastromal or intrascleral route. Thus, dissolving MNs have potential applications in enhancing ocular delivery of both small and macromolecules. |
format | Online Article Text |
id | pubmed-5097091 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Springer US |
record_format | MEDLINE/PubMed |
spelling | pubmed-50970912016-11-21 Rapidly dissolving polymeric microneedles for minimally invasive intraocular drug delivery Thakur, Raghu Raj Singh Tekko, Ismaiel A. Al-Shammari, Farhan Ali, Ahlam A. McCarthy, Helen Donnelly, Ryan F. Drug Deliv Transl Res Original Article In this study, dissolving microneedles (MNs) were used to enhance ocular drug delivery of macromolecules. MNs were fabricated using polyvinylpyrrolidone (PVP) polymer of various molecular weights (MWs) containing three model molecules of increasing MW, namely fluorescein sodium and fluorescein isothiocyanate–dextrans (with MW of 70 k and 150 k Da). Arrays (3 × 3) of PVP MNs with conical shape measuring about 800 μm in height with a 300 μm base diameter, containing the model drugs, were fabricated and characterized for their fracture forces, insertion forces (in the sclera and cornea), depth of penetration (using OCT and confocal imaging), dissolution time and in vitro permeation. The average drug content of the MNs (only in MN shafts) ranged from 0.96 to 9.91 μg, and the average moisture content was below 11 %. High MW PVP produced MNs that can withstand higher forces with minimal reduction in needle height. PVP MNs showed rapid dissolution that ranged from 10 to 180 s, which was dependent upon PVP’s MW. In vitro studies showed significant enhancement of macromolecule permeation when MNs were used, across both the corneal and scleral tissues, in comparison to topically applied aqueous solutions. Confocal images showed that the macromolecules formed depots within the tissues, which led to sustained permeation. However, use of MNs did not significantly benefit the permeation of small molecules; nevertheless, MN application has the potential for drug retention within the selected ocular tissues unlike topical application for small molecules. The material used in the fabrication of the MNs was found to be biocompatible with retinal cells (i.e. ARPE-19). Overall, this study reported the design and fabrication of minimally invasive rapidly dissolving polymeric MN arrays which were able to deliver high MW molecules to the eye via the intrastromal or intrascleral route. Thus, dissolving MNs have potential applications in enhancing ocular delivery of both small and macromolecules. Springer US 2016-10-05 2016 /pmc/articles/PMC5097091/ /pubmed/27709355 http://dx.doi.org/10.1007/s13346-016-0332-9 Text en © The Author(s) 2016 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. |
spellingShingle | Original Article Thakur, Raghu Raj Singh Tekko, Ismaiel A. Al-Shammari, Farhan Ali, Ahlam A. McCarthy, Helen Donnelly, Ryan F. Rapidly dissolving polymeric microneedles for minimally invasive intraocular drug delivery |
title | Rapidly dissolving polymeric microneedles for minimally invasive intraocular drug delivery |
title_full | Rapidly dissolving polymeric microneedles for minimally invasive intraocular drug delivery |
title_fullStr | Rapidly dissolving polymeric microneedles for minimally invasive intraocular drug delivery |
title_full_unstemmed | Rapidly dissolving polymeric microneedles for minimally invasive intraocular drug delivery |
title_short | Rapidly dissolving polymeric microneedles for minimally invasive intraocular drug delivery |
title_sort | rapidly dissolving polymeric microneedles for minimally invasive intraocular drug delivery |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5097091/ https://www.ncbi.nlm.nih.gov/pubmed/27709355 http://dx.doi.org/10.1007/s13346-016-0332-9 |
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