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

• Published in: International journal of pharmaceutics Vol. 661; p. 124411
• Main Authors: Pereira Santos Carvalho, Ivana, Bueno Silva, Letícia, Luis Ferraz do Amaral, Robson, Nader Chrysostomo-Massaro, Tais, Dias de Lima Fragelli, Bruna, Margareth de Almeida Rodolpho, Joice, de Freitas Anibal, Fernanda, Carneiro Borra, Ricardo, Augusto Rizzato Paschoal, Jonas, Abreu Miranda, Mariza, Kenupp Bastos, Jairo, Attié de Castro, Fabíola, Daniely Marcato, Priscyla
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15-08-2024
• Subjects: Animals; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Antitumoral activity; Bladder cancer; Cell Line, Tumor; Cell Survival - drug effects; Chitosan; Drug Carriers - chemistry; Female; Glycoalkaloids; Humans; Lipid-polymer hybrid nanoparticles; Lipids - chemistry; Mice; Mice, Inbred C57BL; Nanoparticles - chemistry; Particle Size; Polymers - chemistry; Solanaceous Alkaloids - administration & dosage; Solanaceous Alkaloids - chemistry; Solanaceous Alkaloids - pharmacology; Solasonine/Solamargine; Urinary Bladder Neoplasms - drug therapy; Urinary Bladder Neoplasms - pathology; Glycoalkaloids; Lipid-polymer hybrid nanoparticles; Solasonine/Solamargine; Chitosan; Antitumoral activity; Bladder cancer
• ISSN: 0378-5173; 1873-3476; 1873-3476
• DOI: 10.1016/j.ijpharm.2024.124411

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•LPHNP with core–shell structures and mucoadhesive properties were used to encapsulate SS/SM.•LPHNP-SS/SM enhanced cytotoxicity in bladder cancer model with modulating apoptosis gene expression.•Treatment with LPHNP-SS/SM significantly reduced tumor volume in an orthotopic bladder cancer model.
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 IC50 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.