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

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Carvalho, Ivana Pereira Santos ; Silva, Leticia Bueno ; do Amaral, Robson Luis Ferraz ; Chrysostomo-Massaro, Tais Nader ; Fragelli, Bruna Dias de Lima ; Rodolpho, Joice Margareth de Almeida ; Anibal, Fernanda de Freitas ; Borra, Ricardo Carneiro ; Paschoal, Jonas Augusto Rizzato ; Miranda, Mariza Abreu ; Bastos, Jairo Kenupp ; de Castro, Fabfola Attie ; Marcato, Priscyla Daniely

• Tipo de documento: Artigo Científico
• Fonte: International Journal of Pharmaceutics; v. 661, p. 14-pg., 2024-07-05.

Resumo

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. (AU)

• Processo FAPESP: 18/13465-5 - Desenvolvimento de nanopartículas poliméricas contendo própolis vermelha brasileira e avaliação antitumoral in vitro e in vivo em cânceres urológicos
• Beneficiário: Priscyla Daniely Marcato Gaspari
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 14/50928-2 - INCT 2014: Nanotecnologia Farmacêutica: uma abordagem transdisciplinar
• Beneficiário: Maria Vitória Lopes Badra Bentley
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 18/16172-9 - Desenvolvimento e caracterização de carreador lipídico nanoestruturado contendo própolis vermelha brasileira em formulações fotoprotetoras
• Beneficiário: Bianca Bueno Fontanezi Dias Mello
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 17/04138-8 - Realização de estudos químicos, analíticos, biológicos, farmacológicos e tecnológicos para preenchimento das lacunas no desenvolvimento do setor de própolis brasileiro
• Beneficiário: Jairo Kenupp Bastos
• Modalidade de apoio: Auxílio à Pesquisa - Temático