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Nanoencapsulated Doxorubicin Prevents Mucositis Development in Mice

Doxorubicin (DOX), a chemotherapy drug successfully used in the therapy of various types of cancer, is currently associated with the mucositis development, an inflammation that can cause ulcerative lesions in the mucosa of the gastrointestinal tract, abdominal pain and secondary infections. To incre...

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Autores principales: Pinto, Cristiane M., Horta, Laila S., Soares, Amanda P., Carvalho, Bárbara A., Ferreira, Enio, Lages, Eduardo B., Ferreira, Lucas A. M., Faraco, André A. G., Santiago, Helton C., Goulart, Gisele A. C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8329927/
https://www.ncbi.nlm.nih.gov/pubmed/34371713
http://dx.doi.org/10.3390/pharmaceutics13071021
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author Pinto, Cristiane M.
Horta, Laila S.
Soares, Amanda P.
Carvalho, Bárbara A.
Ferreira, Enio
Lages, Eduardo B.
Ferreira, Lucas A. M.
Faraco, André A. G.
Santiago, Helton C.
Goulart, Gisele A. C.
author_facet Pinto, Cristiane M.
Horta, Laila S.
Soares, Amanda P.
Carvalho, Bárbara A.
Ferreira, Enio
Lages, Eduardo B.
Ferreira, Lucas A. M.
Faraco, André A. G.
Santiago, Helton C.
Goulart, Gisele A. C.
author_sort Pinto, Cristiane M.
collection PubMed
description Doxorubicin (DOX), a chemotherapy drug successfully used in the therapy of various types of cancer, is currently associated with the mucositis development, an inflammation that can cause ulcerative lesions in the mucosa of the gastrointestinal tract, abdominal pain and secondary infections. To increase the safety of the chemotherapy, we loaded DOX into nanostructured lipid carriers (NLCs). The NLC–DOX was characterized by HPLC, DLS, NTA, Zeta potential, FTIR, DSC, TEM and cryogenic-TEM. The ability of NLC–DOX to control the DOX release was evaluated through in vitro release studies. Moreover, the effect of NLC–DOX on intestinal mucosa was compared to a free DOX solution in C57BL/6 mice. The NLC–DOX showed spherical shape, high drug encapsulation efficiency (84.8 ± 4.6%), high drug loading (55.2 ± 3.4 mg/g) and low average diameter (66.0–78.8 nm). The DSC and FTIR analyses showed high interaction between the NLC components, resulting in controlled drug release. Treatment with NLC–DOX attenuated DOX-induced mucositis in mice, improving shortening on villus height and crypt depth, decreased inflammatory parameters, preserved intestinal permeability and increased expression of tight junctions (ZO-1 and Ocludin). These results indicated that encapsulation of DOX in NLCs is viable and reduces the drug toxicity to mucosal structures.
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spelling pubmed-83299272021-08-04 Nanoencapsulated Doxorubicin Prevents Mucositis Development in Mice Pinto, Cristiane M. Horta, Laila S. Soares, Amanda P. Carvalho, Bárbara A. Ferreira, Enio Lages, Eduardo B. Ferreira, Lucas A. M. Faraco, André A. G. Santiago, Helton C. Goulart, Gisele A. C. Pharmaceutics Article Doxorubicin (DOX), a chemotherapy drug successfully used in the therapy of various types of cancer, is currently associated with the mucositis development, an inflammation that can cause ulcerative lesions in the mucosa of the gastrointestinal tract, abdominal pain and secondary infections. To increase the safety of the chemotherapy, we loaded DOX into nanostructured lipid carriers (NLCs). The NLC–DOX was characterized by HPLC, DLS, NTA, Zeta potential, FTIR, DSC, TEM and cryogenic-TEM. The ability of NLC–DOX to control the DOX release was evaluated through in vitro release studies. Moreover, the effect of NLC–DOX on intestinal mucosa was compared to a free DOX solution in C57BL/6 mice. The NLC–DOX showed spherical shape, high drug encapsulation efficiency (84.8 ± 4.6%), high drug loading (55.2 ± 3.4 mg/g) and low average diameter (66.0–78.8 nm). The DSC and FTIR analyses showed high interaction between the NLC components, resulting in controlled drug release. Treatment with NLC–DOX attenuated DOX-induced mucositis in mice, improving shortening on villus height and crypt depth, decreased inflammatory parameters, preserved intestinal permeability and increased expression of tight junctions (ZO-1 and Ocludin). These results indicated that encapsulation of DOX in NLCs is viable and reduces the drug toxicity to mucosal structures. MDPI 2021-07-04 /pmc/articles/PMC8329927/ /pubmed/34371713 http://dx.doi.org/10.3390/pharmaceutics13071021 Text en © 2021 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
Pinto, Cristiane M.
Horta, Laila S.
Soares, Amanda P.
Carvalho, Bárbara A.
Ferreira, Enio
Lages, Eduardo B.
Ferreira, Lucas A. M.
Faraco, André A. G.
Santiago, Helton C.
Goulart, Gisele A. C.
Nanoencapsulated Doxorubicin Prevents Mucositis Development in Mice
title Nanoencapsulated Doxorubicin Prevents Mucositis Development in Mice
title_full Nanoencapsulated Doxorubicin Prevents Mucositis Development in Mice
title_fullStr Nanoencapsulated Doxorubicin Prevents Mucositis Development in Mice
title_full_unstemmed Nanoencapsulated Doxorubicin Prevents Mucositis Development in Mice
title_short Nanoencapsulated Doxorubicin Prevents Mucositis Development in Mice
title_sort nanoencapsulated doxorubicin prevents mucositis development in mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8329927/
https://www.ncbi.nlm.nih.gov/pubmed/34371713
http://dx.doi.org/10.3390/pharmaceutics13071021
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