Evaluation of in vivo and in vitro efficacy of solasonine/solamargine-loaded lipid-polymer hybrid nanoparticles against bladder cancer.

Autor: Pereira Santos Carvalho I; GNanoBio, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, São Paulo, Brazil., Bueno Silva L; GNanoBio, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, São Paulo, Brazil., Luis Ferraz do Amaral R; School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, São Paulo, Brazil., Nader Chrysostomo-Massaro T; GNanoBio, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, São Paulo, Brazil., Dias de Lima Fragelli B; Center for Development of Functional Materials, Federal University of São Carlos, São Carlos, São Paulo, Brazil., Margareth de Almeida Rodolpho J; Laboratory of Inflammation and Infectious Diseases, Department of Morphology and Pathology, Federal University of São Carlos, São Carlos, São Paulo, Brazil., de Freitas Anibal F; Laboratory of Inflammation and Infectious Diseases, Department of Morphology and Pathology, Federal University of São Carlos, São Carlos, São Paulo, Brazil., Carneiro Borra R; Laboratory of Inflammation and Infectious Diseases, Department of Morphology and Pathology, Federal University of São Carlos, São Carlos, São Paulo, Brazil., Augusto Rizzato Paschoal J; School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, São Paulo, Brazil., Abreu Miranda M; Interdisciplinary Center for Biotechnology Research, University of Florida, Gainesville, United States., Kenupp Bastos J; School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, São Paulo, Brazil., Attié de Castro F; Department of Clinical Analyses, Toxicology and Food Science, School of Pharmaceutical Science of Ribeirão Preto, University of São Paulo, São Paulo, Brazil., Daniely Marcato P; GNanoBio, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, São Paulo, Brazil. Electronic address: pmarcato@fcfrp.usp.br.
Jazyk: angličtina
Zdroj: International journal of pharmaceutics [Int J Pharm] 2024 Aug 15; Vol. 661, pp. 124411. Date of Electronic Publication: 2024 Jul 02.
DOI: 10.1016/j.ijpharm.2024.124411
Abstrakt: Solasonine (SS) and solamargine (SM) are alkaloids known for their antioxidant and anticancer properties, which can be further enhanced by encapsulating them in nanoparticles. This led to a study on the potential therapeutic benefits of SS and SM against bladder cancer when encapsulated in lipid-polymer hybrid nanoparticles (LPHNP). The LPHNP loaded with SS/SM were prepared using the emulsion and sonication method and their physical-chemical properties characterized. The biological effects of these nanoparticles were then tested in both 2D and 3D bladder cancer cell culture models, as well as in a syngeneic orthotopic mouse model based on the MB49 cell line and ethanol epithelial injury. The LPHNP-SS/SM had an average size of 130 nm, a polydispersity index of 0.22 and a positive zeta potential, indicating the presence of chitosan coating on the nanoparticle surface. The dispersion of LPHNP-SS/SM was found to be monodispersed with a span index of 0.539, as measured by nanoparticle tracking analysis (NTA). The recrystallization index, calculated from DSC data, was higher for the LPHNP-SS/SM compared to LPHNPs alone, confirming the presence of alkaloids within the lipid matrix. The encapsulation efficiency (EE%) was also high, with 91.08 % for SS and 88.35 % for SM. Morphological analysis by AFM and Cryo-TEM revealed that the nanoparticles had a spherical shape and core-shell structure. The study showed that the LPHNP-SS/SM exhibited mucoadhesive properties by physically interacting with mucin, suggesting a potential improvement in interaction with mucous membrane. Both the free and nanoencapsulated SS/SM demonstrated dose-dependent cytotoxicity against bladder cancer cell lines after 24 and 72 h of treatment. In 3D bladder cell culture, the nanoencapsulated SS/SM showed an IC 50 two-fold lower than free SS/SM. In vivo studies, the LPHNP-SS/SM displayed an antitumoral effect at high doses, leading to a significant reduction in bladder volume compared to the positive control. However, there were observed instances of systemic toxicity and liver damage, indicated by elevated levels of transaminases (TGO and TGP). Overall, these results indicate that the LPHNPs effectively encapsulated SS/SM, showing high encapsulation efficiency and stability, along with promising in vitro and in vivo antitumoral effects against bladder cancer. Further evaluation of its systemic toxicity effects is necessary to ensure its safety and efficacy for potential clinical application.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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