pH-responsive and folate-coated liposomes encapsulating irinotecan as an alternative to improve efficacy of colorectal cancer treatment

Irinotecan (IRN) is a semisynthetic derivative of camptothecin that acts as a topoisomerase I inhibitor. IRN is used worldwide for the treatment of several types of cancer, including colorectal cancer, however its use can lead to serious adverse effects, as diarrhea and myelosuppression. Liposomes a...

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Autores principales:	Shirleide Santos Nunes, Sued Eustaquio Mendes Miranda, Juliana de Oliveira Silva, Renata Salgado Fernandes, Janaína de Alcântara Lemos, Carolina de Aguiar Ferreira, Danyelle M. Townsend, Geovanni Dantas Cassali, Mônica Cristina Oliveira, André Luís Branco de Barros
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Liposomes Irinotecan, polyethylene glycol Antitumor activity Folate-coated Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/1d302669881041af945832310c5196dc
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spelling	oai:doaj.org-article:1d302669881041af945832310c5196dc2021-11-14T04:29:37ZpH-responsive and folate-coated liposomes encapsulating irinotecan as an alternative to improve efficacy of colorectal cancer treatment0753-332210.1016/j.biopha.2021.112317https://doaj.org/article/1d302669881041af945832310c5196dc2021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S075333222101101Xhttps://doaj.org/toc/0753-3322Irinotecan (IRN) is a semisynthetic derivative of camptothecin that acts as a topoisomerase I inhibitor. IRN is used worldwide for the treatment of several types of cancer, including colorectal cancer, however its use can lead to serious adverse effects, as diarrhea and myelosuppression. Liposomes are widely used as drug delivery systems that can improve chemotherapeutic activity and decrease side effects. Liposomes can also be pH-sensitive to release its content preferentially in acidic environments, like tumors, and be surface-functionalized for targeting purposes. Herein, we developed a folate-coated pH-sensitive liposome as a drug delivery system for IRN to reach improved tumor therapy without potential adverse events. Liposomes were prepared containing IRN and characterized for particle size, polydispersity index, zeta potential, concentration, encapsulation, cellular uptake, and release profile. Antitumor activity was investigated in a murine model of colorectal cancer, and its toxicity was evaluated by hematological/biochemical tests and histological analysis of main organs. The results showed vesicles smaller than 200 nm with little dispersion, a surface charge close to neutral, and high encapsulation rate of over 90%. The system demonstrated prolonged and sustained release in pH-dependent manner with high intracellular drug delivery capacity. Importantly, the folate-coated pH-sensitive formulation had significantly better antitumor activity than the pH-dependent system only or the free drug. Tumor tissue of IRN-containing groups presented large areas of necrosis. Furthermore, no evidence of systemic toxicity was found for the groups investigated. Thus, our developed nanodrug IRN delivery system can potentially be an alternative to conventional colorectal cancer treatment.Shirleide Santos NunesSued Eustaquio Mendes MirandaJuliana de Oliveira SilvaRenata Salgado FernandesJanaína de Alcântara LemosCarolina de Aguiar FerreiraDanyelle M. TownsendGeovanni Dantas CassaliMônica Cristina OliveiraAndré Luís Branco de BarrosElsevierarticleLiposomesIrinotecan, polyethylene glycolAntitumor activityFolate-coatedTherapeutics. PharmacologyRM1-950ENBiomedicine & Pharmacotherapy, Vol 144, Iss , Pp 112317- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Liposomes Irinotecan, polyethylene glycol Antitumor activity Folate-coated Therapeutics. Pharmacology RM1-950
spellingShingle	Liposomes Irinotecan, polyethylene glycol Antitumor activity Folate-coated Therapeutics. Pharmacology RM1-950 Shirleide Santos Nunes Sued Eustaquio Mendes Miranda Juliana de Oliveira Silva Renata Salgado Fernandes Janaína de Alcântara Lemos Carolina de Aguiar Ferreira Danyelle M. Townsend Geovanni Dantas Cassali Mônica Cristina Oliveira André Luís Branco de Barros pH-responsive and folate-coated liposomes encapsulating irinotecan as an alternative to improve efficacy of colorectal cancer treatment
description	Irinotecan (IRN) is a semisynthetic derivative of camptothecin that acts as a topoisomerase I inhibitor. IRN is used worldwide for the treatment of several types of cancer, including colorectal cancer, however its use can lead to serious adverse effects, as diarrhea and myelosuppression. Liposomes are widely used as drug delivery systems that can improve chemotherapeutic activity and decrease side effects. Liposomes can also be pH-sensitive to release its content preferentially in acidic environments, like tumors, and be surface-functionalized for targeting purposes. Herein, we developed a folate-coated pH-sensitive liposome as a drug delivery system for IRN to reach improved tumor therapy without potential adverse events. Liposomes were prepared containing IRN and characterized for particle size, polydispersity index, zeta potential, concentration, encapsulation, cellular uptake, and release profile. Antitumor activity was investigated in a murine model of colorectal cancer, and its toxicity was evaluated by hematological/biochemical tests and histological analysis of main organs. The results showed vesicles smaller than 200 nm with little dispersion, a surface charge close to neutral, and high encapsulation rate of over 90%. The system demonstrated prolonged and sustained release in pH-dependent manner with high intracellular drug delivery capacity. Importantly, the folate-coated pH-sensitive formulation had significantly better antitumor activity than the pH-dependent system only or the free drug. Tumor tissue of IRN-containing groups presented large areas of necrosis. Furthermore, no evidence of systemic toxicity was found for the groups investigated. Thus, our developed nanodrug IRN delivery system can potentially be an alternative to conventional colorectal cancer treatment.
format	article
author	Shirleide Santos Nunes Sued Eustaquio Mendes Miranda Juliana de Oliveira Silva Renata Salgado Fernandes Janaína de Alcântara Lemos Carolina de Aguiar Ferreira Danyelle M. Townsend Geovanni Dantas Cassali Mônica Cristina Oliveira André Luís Branco de Barros
author_facet	Shirleide Santos Nunes Sued Eustaquio Mendes Miranda Juliana de Oliveira Silva Renata Salgado Fernandes Janaína de Alcântara Lemos Carolina de Aguiar Ferreira Danyelle M. Townsend Geovanni Dantas Cassali Mônica Cristina Oliveira André Luís Branco de Barros
author_sort	Shirleide Santos Nunes
title	pH-responsive and folate-coated liposomes encapsulating irinotecan as an alternative to improve efficacy of colorectal cancer treatment
title_short	pH-responsive and folate-coated liposomes encapsulating irinotecan as an alternative to improve efficacy of colorectal cancer treatment
title_full	pH-responsive and folate-coated liposomes encapsulating irinotecan as an alternative to improve efficacy of colorectal cancer treatment
title_fullStr	pH-responsive and folate-coated liposomes encapsulating irinotecan as an alternative to improve efficacy of colorectal cancer treatment
title_full_unstemmed	pH-responsive and folate-coated liposomes encapsulating irinotecan as an alternative to improve efficacy of colorectal cancer treatment
title_sort	ph-responsive and folate-coated liposomes encapsulating irinotecan as an alternative to improve efficacy of colorectal cancer treatment
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/1d302669881041af945832310c5196dc
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pH-responsive and folate-coated liposomes encapsulating irinotecan as an alternative to improve efficacy of colorectal cancer treatment

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