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Dually Responsive Poly(N-vinylcaprolactam)-b-poly(dimethylsiloxane)-b-poly(N-vinylcaprolactam) Polymersomes for Controlled Delivery

Limited tissue selectivity and targeting of anticancer therapeutics in systemic administration can produce harmful side effects in the body. Various polymer nano-vehicles have been developed to encapsulate therapeutics and prevent premature drug release. Dually responsive polymeric vesicles (polymer...

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Autores principales: Kozlovskaya, Veronika, Yang, Yiming, Liu, Fei, Ingle, Kevin, Ahmad, Aftab, Halade, Ganesh V., Kharlampieva, Eugenia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9182360/
https://www.ncbi.nlm.nih.gov/pubmed/35684423
http://dx.doi.org/10.3390/molecules27113485
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author Kozlovskaya, Veronika
Yang, Yiming
Liu, Fei
Ingle, Kevin
Ahmad, Aftab
Halade, Ganesh V.
Kharlampieva, Eugenia
author_facet Kozlovskaya, Veronika
Yang, Yiming
Liu, Fei
Ingle, Kevin
Ahmad, Aftab
Halade, Ganesh V.
Kharlampieva, Eugenia
author_sort Kozlovskaya, Veronika
collection PubMed
description Limited tissue selectivity and targeting of anticancer therapeutics in systemic administration can produce harmful side effects in the body. Various polymer nano-vehicles have been developed to encapsulate therapeutics and prevent premature drug release. Dually responsive polymeric vesicles (polymersomes) assembled from temperature-/pH-sensitive block copolymers are particularly interesting for the delivery of encapsulated therapeutics to targeted tumors and inflamed tissues. We have previously demonstrated that temperature-responsive poly(N-vinylcaprolactam) (PVCL)-b-poly(dimethylsiloxane) (PDMS)-b-PVCL polymersomes exhibit high loading efficiency of anticancer therapeutics in physiological conditions. However, the in-vivo toxicity of these polymersomes as biocompatible materials has not yet been explored. Nevertheless, developing an advanced therapeutic nanocarrier must provide the knowledge of possible risks from the material’s toxicity to support its future clinical research in humans. Herein, we studied pH-induced degradation of PVCL(10)-b-PDMS(65)-b-PVCL(10) vesicles in-situ and their dually (pH- and temperature-) responsive release of the anticancer drug, doxorubicin, using NMR, DLS, TEM, and absorbance spectroscopy. The toxic potential of the polymersomes was evaluated in-vivo by intravenous injection (40 mg kg(−1) single dose) of PVCL(10)-PDMS(65)-PVCL(10) vesicles to mice. The sub-acute toxicity study (14 days) included gravimetric, histological, and hematological analyses and provided evidence for good biocompatibility and non-toxicity of the biomaterial. These results show the potential of these vesicles to be used in clinical research.
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spelling pubmed-91823602022-06-10 Dually Responsive Poly(N-vinylcaprolactam)-b-poly(dimethylsiloxane)-b-poly(N-vinylcaprolactam) Polymersomes for Controlled Delivery Kozlovskaya, Veronika Yang, Yiming Liu, Fei Ingle, Kevin Ahmad, Aftab Halade, Ganesh V. Kharlampieva, Eugenia Molecules Article Limited tissue selectivity and targeting of anticancer therapeutics in systemic administration can produce harmful side effects in the body. Various polymer nano-vehicles have been developed to encapsulate therapeutics and prevent premature drug release. Dually responsive polymeric vesicles (polymersomes) assembled from temperature-/pH-sensitive block copolymers are particularly interesting for the delivery of encapsulated therapeutics to targeted tumors and inflamed tissues. We have previously demonstrated that temperature-responsive poly(N-vinylcaprolactam) (PVCL)-b-poly(dimethylsiloxane) (PDMS)-b-PVCL polymersomes exhibit high loading efficiency of anticancer therapeutics in physiological conditions. However, the in-vivo toxicity of these polymersomes as biocompatible materials has not yet been explored. Nevertheless, developing an advanced therapeutic nanocarrier must provide the knowledge of possible risks from the material’s toxicity to support its future clinical research in humans. Herein, we studied pH-induced degradation of PVCL(10)-b-PDMS(65)-b-PVCL(10) vesicles in-situ and their dually (pH- and temperature-) responsive release of the anticancer drug, doxorubicin, using NMR, DLS, TEM, and absorbance spectroscopy. The toxic potential of the polymersomes was evaluated in-vivo by intravenous injection (40 mg kg(−1) single dose) of PVCL(10)-PDMS(65)-PVCL(10) vesicles to mice. The sub-acute toxicity study (14 days) included gravimetric, histological, and hematological analyses and provided evidence for good biocompatibility and non-toxicity of the biomaterial. These results show the potential of these vesicles to be used in clinical research. MDPI 2022-05-28 /pmc/articles/PMC9182360/ /pubmed/35684423 http://dx.doi.org/10.3390/molecules27113485 Text en © 2022 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
Kozlovskaya, Veronika
Yang, Yiming
Liu, Fei
Ingle, Kevin
Ahmad, Aftab
Halade, Ganesh V.
Kharlampieva, Eugenia
Dually Responsive Poly(N-vinylcaprolactam)-b-poly(dimethylsiloxane)-b-poly(N-vinylcaprolactam) Polymersomes for Controlled Delivery
title Dually Responsive Poly(N-vinylcaprolactam)-b-poly(dimethylsiloxane)-b-poly(N-vinylcaprolactam) Polymersomes for Controlled Delivery
title_full Dually Responsive Poly(N-vinylcaprolactam)-b-poly(dimethylsiloxane)-b-poly(N-vinylcaprolactam) Polymersomes for Controlled Delivery
title_fullStr Dually Responsive Poly(N-vinylcaprolactam)-b-poly(dimethylsiloxane)-b-poly(N-vinylcaprolactam) Polymersomes for Controlled Delivery
title_full_unstemmed Dually Responsive Poly(N-vinylcaprolactam)-b-poly(dimethylsiloxane)-b-poly(N-vinylcaprolactam) Polymersomes for Controlled Delivery
title_short Dually Responsive Poly(N-vinylcaprolactam)-b-poly(dimethylsiloxane)-b-poly(N-vinylcaprolactam) Polymersomes for Controlled Delivery
title_sort dually responsive poly(n-vinylcaprolactam)-b-poly(dimethylsiloxane)-b-poly(n-vinylcaprolactam) polymersomes for controlled delivery
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9182360/
https://www.ncbi.nlm.nih.gov/pubmed/35684423
http://dx.doi.org/10.3390/molecules27113485
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