Amparo Tatiane Roquete, Anunciação Kamila de Fátima da, Almeida Tamires Cunha, Sousa Lucas Resende Dutra, Xavier Viviane Flores, Seibert Janaína Brandão, Barboza Ana Paula Moreira, Vieira Paula Melo de Abreu, Dos Santos Orlando David Henrique, da Silva Glenda Nicioli, Brandão Geraldo Célio
Postgraduate Program on Pharmaceutical Sciences, Federal University of Ouro Preto, Ouro Preto 35402-173, Brazil.
Postgraduate Program on Biological Sciences, Federal University of Ouro Preto, Ouro Preto 35402-173, Brazil.
Pharmaceutics. 2025 Jul 2;17(7):868. doi: 10.3390/pharmaceutics17070868.
Lapachol is a naturally occurring prenylated naphthoquinone with antiproliferative effects. However, its clinical application remains limited due to several factors, including poor water solubility, low bioavailability, and adverse effects. The development of chitosan-based nanoparticles holds promise in overcoming these challenges and has emerged as a potential nanocarrier for cancer therapy, including bladder cancer. The objective of this study was to develop and evaluate the effects of chitosan nanoparticles on bladder tumor cell lines. The nanoemulsion was prepared using the hot homogenization method, while the chitosan nanoparticles were obtained through the ionic gelation technique. The nanoformulations were characterized in terms of particle size and polydispersity index (PDI) using photon correlation spectroscopy, and zeta potential by electrophoretic mobility. Encapsulation efficiency was determined by ultracentrifugation, and the drug release was analyzed using the dialysis method. The antineoplastic potential was assessed using the MTT assay, and the safety profile was assessed through ex vivo analysis. Cellular uptake was determined by fluorescence microscopy. The study demonstrated that both the chitosan-based nanoemulsion and nanospheres encapsulating lapachol exhibited appropriate particle sizes (around 160 nm), high encapsulation efficiency (>90%), and a controlled release profile (Korsmeyer-Peppas model). These nanoemulsion systems enhanced the antiproliferative activity of lapachol in bladder tumor cells, with the nanospheres showing superior cellular uptake. Histopathological analysis indicated the safety of the formulations when administered intravesically. The results suggest that chitosan nanoparticles may represent a promising alternative for bladder cancer treatment.
拉帕醇是一种天然存在的具有抗增殖作用的异戊烯基萘醌。然而，由于多种因素，包括水溶性差、生物利用度低和不良反应，其临床应用仍然有限。基于壳聚糖的纳米颗粒的开发有望克服这些挑战，并已成为包括膀胱癌在内的癌症治疗的潜在纳米载体。本研究的目的是开发并评估壳聚糖纳米颗粒对膀胱肿瘤细胞系的影响。纳米乳剂采用热均质法制备，而壳聚糖纳米颗粒则通过离子凝胶技术获得。使用光子相关光谱法对纳米制剂的粒径和多分散指数（PDI）进行表征，通过电泳迁移率测定zeta电位。通过超速离心法测定包封率，并使用透析法分析药物释放。使用MTT法评估抗肿瘤潜力，并通过体外分析评估安全性。通过荧光显微镜确定细胞摄取情况。该研究表明，包封拉帕醇的基于壳聚糖的纳米乳剂和纳米球均表现出合适的粒径（约160nm）、高包封率（>90%）和控释曲线（Korsmeyer-Peppas模型）。这些纳米乳剂系统增强了拉帕醇在膀胱肿瘤细胞中的抗增殖活性，纳米球表现出更高的细胞摄取。组织病理学分析表明膀胱内给药时制剂的安全性。结果表明，壳聚糖纳米颗粒可能是膀胱癌治疗的一种有前景的替代方法。
