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

Autor: Nunes SS; Department of Pharmaceutical Products, Faculty of Pharmacy, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, 31270-901 Belo Horizonte, Minas Gerais, Brazil., Miranda SEM; Department of Pharmaceutical Products, Faculty of Pharmacy, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, 31270-901 Belo Horizonte, Minas Gerais, Brazil., de Oliveira Silva J; Department of Pharmaceutical Products, Faculty of Pharmacy, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, 31270-901 Belo Horizonte, Minas Gerais, Brazil., Fernandes RS; Department of Pharmaceutical Products, Faculty of Pharmacy, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, 31270-901 Belo Horizonte, Minas Gerais, Brazil., de Alcântara Lemos J; Department of Pharmaceutical Products, Faculty of Pharmacy, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, 31270-901 Belo Horizonte, Minas Gerais, Brazil., de Aguiar Ferreira C; Department of Medical Physics, University of Wisconsin-Madison, Madison, WI 53705, USA., Townsend DM; Department of Drug Discovery and Pharmaceutical Sciences, College of Pharmacy, Medical University of South Carolina, USA., Cassali GD; Department of General Pathology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, 31270-901 Belo Horizonte, Minas Gerais, Brazil., Oliveira MC; Department of Pharmaceutical Products, Faculty of Pharmacy, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, 31270-901 Belo Horizonte, Minas Gerais, Brazil., Branco de Barros AL; Department of Clinical and Toxicological Analyses, Faculty of Pharmacy, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, 31270-901 Belo Horizonte, Minas Gerais, Brazil. Electronic address: brancodebarros@yahoo.com.br.
Jazyk: angličtina
Zdroj: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie [Biomed Pharmacother] 2021 Dec; Vol. 144, pp. 112317. Date of Electronic Publication: 2021 Oct 08.
DOI: 10.1016/j.biopha.2021.112317
Abstrakt: 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.
(Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)
Databáze: MEDLINE
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