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Multilayered Polyurethane/Poly(vinyl alcohol) Nanofibrous Mats for Local Topotecan Delivery as a Potential Retinoblastoma Treatment

Local chemotherapy using polymer drug delivery systems has the potential to treat some cancers, including intraocular retinoblastoma, which is difficult to treat with systemically delivered drugs. Well-designed carriers can provide the required drug concentration at the target site over a prolonged...

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Autores principales: Hobzova, Radka, Sirc, Jakub, Shrestha, Kusum, Mudrova, Barbora, Bosakova, Zuzana, Slouf, Miroslav, Munzarova, Marcela, Hrabeta, Jan, Feglarova, Tereza, Cocarta, Ana-Irina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10222511/
https://www.ncbi.nlm.nih.gov/pubmed/37242640
http://dx.doi.org/10.3390/pharmaceutics15051398
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author Hobzova, Radka
Sirc, Jakub
Shrestha, Kusum
Mudrova, Barbora
Bosakova, Zuzana
Slouf, Miroslav
Munzarova, Marcela
Hrabeta, Jan
Feglarova, Tereza
Cocarta, Ana-Irina
author_facet Hobzova, Radka
Sirc, Jakub
Shrestha, Kusum
Mudrova, Barbora
Bosakova, Zuzana
Slouf, Miroslav
Munzarova, Marcela
Hrabeta, Jan
Feglarova, Tereza
Cocarta, Ana-Irina
author_sort Hobzova, Radka
collection PubMed
description Local chemotherapy using polymer drug delivery systems has the potential to treat some cancers, including intraocular retinoblastoma, which is difficult to treat with systemically delivered drugs. Well-designed carriers can provide the required drug concentration at the target site over a prolonged time, reduce the overall drug dose needed, and suppress severe side effects. Herein, nanofibrous carriers of the anticancer agent topotecan (TPT) with a multilayered structure composed of a TPT-loaded inner layer of poly(vinyl alcohol) (PVA) and outer covering layers of polyurethane (PUR) are proposed. Scanning electron microscopy showed homogeneous incorporation of TPT into the PVA nanofibers. HPLC-FLD proved the good loading efficiency of TPT (≥85%) with a content of the pharmacologically active lactone TPT of more than 97%. In vitro release experiments demonstrated that the PUR cover layers effectively reduced the initial burst release of hydrophilic TPT. In a 3-round experiment with human retinoblastoma cells (Y-79), TPT showed prolonged release from the sandwich-structured nanofibers compared with that from a PVA monolayer, with significantly enhanced cytotoxic effects as a result of an increase in the PUR layer thickness. The presented PUR-PVA/TPT-PUR nanofibers appear to be promising carriers of active TPT lactone that could be useful for local cancer therapy.
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spelling pubmed-102225112023-05-28 Multilayered Polyurethane/Poly(vinyl alcohol) Nanofibrous Mats for Local Topotecan Delivery as a Potential Retinoblastoma Treatment Hobzova, Radka Sirc, Jakub Shrestha, Kusum Mudrova, Barbora Bosakova, Zuzana Slouf, Miroslav Munzarova, Marcela Hrabeta, Jan Feglarova, Tereza Cocarta, Ana-Irina Pharmaceutics Article Local chemotherapy using polymer drug delivery systems has the potential to treat some cancers, including intraocular retinoblastoma, which is difficult to treat with systemically delivered drugs. Well-designed carriers can provide the required drug concentration at the target site over a prolonged time, reduce the overall drug dose needed, and suppress severe side effects. Herein, nanofibrous carriers of the anticancer agent topotecan (TPT) with a multilayered structure composed of a TPT-loaded inner layer of poly(vinyl alcohol) (PVA) and outer covering layers of polyurethane (PUR) are proposed. Scanning electron microscopy showed homogeneous incorporation of TPT into the PVA nanofibers. HPLC-FLD proved the good loading efficiency of TPT (≥85%) with a content of the pharmacologically active lactone TPT of more than 97%. In vitro release experiments demonstrated that the PUR cover layers effectively reduced the initial burst release of hydrophilic TPT. In a 3-round experiment with human retinoblastoma cells (Y-79), TPT showed prolonged release from the sandwich-structured nanofibers compared with that from a PVA monolayer, with significantly enhanced cytotoxic effects as a result of an increase in the PUR layer thickness. The presented PUR-PVA/TPT-PUR nanofibers appear to be promising carriers of active TPT lactone that could be useful for local cancer therapy. MDPI 2023-05-03 /pmc/articles/PMC10222511/ /pubmed/37242640 http://dx.doi.org/10.3390/pharmaceutics15051398 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Hobzova, Radka
Sirc, Jakub
Shrestha, Kusum
Mudrova, Barbora
Bosakova, Zuzana
Slouf, Miroslav
Munzarova, Marcela
Hrabeta, Jan
Feglarova, Tereza
Cocarta, Ana-Irina
Multilayered Polyurethane/Poly(vinyl alcohol) Nanofibrous Mats for Local Topotecan Delivery as a Potential Retinoblastoma Treatment
title Multilayered Polyurethane/Poly(vinyl alcohol) Nanofibrous Mats for Local Topotecan Delivery as a Potential Retinoblastoma Treatment
title_full Multilayered Polyurethane/Poly(vinyl alcohol) Nanofibrous Mats for Local Topotecan Delivery as a Potential Retinoblastoma Treatment
title_fullStr Multilayered Polyurethane/Poly(vinyl alcohol) Nanofibrous Mats for Local Topotecan Delivery as a Potential Retinoblastoma Treatment
title_full_unstemmed Multilayered Polyurethane/Poly(vinyl alcohol) Nanofibrous Mats for Local Topotecan Delivery as a Potential Retinoblastoma Treatment
title_short Multilayered Polyurethane/Poly(vinyl alcohol) Nanofibrous Mats for Local Topotecan Delivery as a Potential Retinoblastoma Treatment
title_sort multilayered polyurethane/poly(vinyl alcohol) nanofibrous mats for local topotecan delivery as a potential retinoblastoma treatment
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10222511/
https://www.ncbi.nlm.nih.gov/pubmed/37242640
http://dx.doi.org/10.3390/pharmaceutics15051398
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