Nose-to-brain delivery of simvastatin mediated by chitosan-coated lipid-core nanocapsules allows for the treatment of glioblastoma in vivo.

Autor: Bruinsmann FA; Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Porto Alegre 90610-000, Brazil., de Cristo Soares Alves A; Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Porto Alegre 90610-000, Brazil., de Fraga Dias A; Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Universidade Federal do Rio Grande do Sul, Porto Alegre 90035 000, Brazil., Lopes Silva LF; Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Universidade Federal do Rio Grande do Sul, Porto Alegre 90035 000, Brazil., Visioli F; Programa de Pós-Graduação em Odontologia, Faculdade de Odontologia, Universidade Federal do Rio Grande do Sul, Porto Alegre 90035-003, Brazil., Raffin Pohlmann A; Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Porto Alegre 90610-000, Brazil., Figueiró F; Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Universidade Federal do Rio Grande do Sul, Porto Alegre 90035 000, Brazil; Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre 90035-003, Brazil., Sonvico F; Food and Drug Department, University of Parma, Parco Area delle Scienze 27/a, 43124 Parma, Italy; Interdepartmental Centre for Innovation in Health Products - Biopharmanet-TEC, University of Parma, Padiglione 33, Campus Universitario, 43124 Parma, PR, Italy. Electronic address: fabio.sonvico@unipr.it., Stanisçuaski Guterres S; Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Porto Alegre 90610-000, Brazil. Electronic address: silvia.guterres@ufrgs.br.
Jazyk: angličtina
Zdroj: International journal of pharmaceutics [Int J Pharm] 2022 Mar 25; Vol. 616, pp. 121563. Date of Electronic Publication: 2022 Feb 10.
DOI: 10.1016/j.ijpharm.2022.121563
Abstrakt: Glioblastoma is the most common and lethal malignant brain tumor. Despite simvastatin (SVT) showing potential anticancer properties, its antitumoral effect against glioblastoma appears limited when the conventional oral administration route is selected. As a consequence, nose-to-brain delivery has been proposed as an alternative route to deliver SVT into the brain. This study aimed to prepare chitosan-coated simvastatin-loaded lipid-core nanocapsules (LNC SVT-chit ) suitable for nose-to-brain delivery and capable of fostering antitumor effects against glioblastoma both in vitro and in vivo. Results showed that the nanocapsules present adequate particle size (mean diameter below 200 nm), narrow particle size distribution (PDI < 0.2), positive zeta potential and high encapsulation efficiency (nearly 100%). In vitro cytotoxicity of LNC SVT-chit was comparable to non-encapsulated SVT in C6 rat glioma cells, whereas LNC SVT-chit were more cytotoxic than non-encapsulated SVT after 72 h of incubation against U-138 MG human glioblastoma cell line. In studies carried out in rats, LNC SVT-chit significantly enhanced the amount of drug in rat brain tissue after intranasal administration (2.4-fold) when compared with free SVT. Moreover, LNC SVT-chit promoted a significant decrease in tumor growth and malignancy in glioma-bearing rats in comparison to control and free SVT groups. Additionally, LNC SVT-chit did not cause any toxicity in treated rats. Considered overall, the results demonstrated that the nose-to-brain administration of LNC SVT-chit represents a novel potential strategy for glioblastoma treatment.
(Copyright © 2022. Published by Elsevier B.V.)
Databáze: MEDLINE
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