茄碱 (SS) 和茄边碱 (SM) 是生物碱，以其抗氧化和抗癌特性而闻名，通过将它们封装在纳米颗粒中可以进一步增强这些特性。这引发了一项关于 SS 和 SM 封装在脂质聚合物混合纳米粒子 (LPHNP) 中时对膀胱癌的潜在治疗效果的研究。采用乳液法和超声法制备了负载SS/SM的LPHNP，并对其物理化学性质进行了表征。然后在 2D 和 3D 膀胱癌细胞培养模型以及基于 MB49 细胞系和乙醇上皮损伤的同基因原位小鼠模型中测试了这些纳米颗粒的生物效应。 LPHNP-SS/SM的平均尺寸为130nm，多分散指数为0.22，zeta电位为正，表明纳米颗粒表面存在壳聚糖涂层。通过纳米颗粒跟踪分析 (NTA) 测量，发现 LPHNP-SS/SM 的分散体是单分散的，跨度指数为 0.539。根据 DSC 数据计算得出，LPHNP-SS/SM 的重结晶指数高于单独的 LPHNP，这证实了脂质基质中存在生物碱。封装效率（EE%）也很高，SS 为 91.08%，SM 为 88.35%。 AFM 和 Cryo-TEM 的形态分析表明纳米颗粒具有球形和核壳结构。研究表明，LPHNP-SS/SM 通过与粘蛋白物理相互作用而表现出粘膜粘附特性​​，这表明与粘膜相互作用的潜在改善。治疗 24 小时和 72 小时后，游离的 SS/SM 和纳米封装的 SS/SM 均表现出针对膀胱癌细胞系的剂量依赖性细胞毒性。在 3D 膀胱细胞培养中，纳米封装的 SS/SM 显示出比游离 SS/SM 低两倍的 IC50。体内研究中，LPHNP-SS/SM 在高剂量下表现出抗肿瘤作用，与阳性对照相比，导致膀胱体积显着减少。然而，也观察到了全身毒性和肝损伤的情况，表现为转氨酶（TGO 和 TGP）水平升高。总的来说，这些结果表明LPHNPs有效地封装了SS/SM，表现出高封装效率和稳定性，并且在体外和体内对膀胱癌具有良好的抗肿瘤作用。有必要进一步评估其全身毒性作用，以确保其潜在临床应用的安全性和有效性。版权所有 © 2024。由 Elsevier B.V. 出版。

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.Copyright © 2024. Published by Elsevier B.V.