Pharmaceutical Nanotechnology Laboratory, Universidade Estadual do Centro-Oeste, Alameda Élio Antonio Dalla Vecchia, 838, CEP 85040-167 Guarapuava, PR, Brazil.
Pharmaceutical Nanotechnology Laboratory, Universidade Estadual do Centro-Oeste, Alameda Élio Antonio Dalla Vecchia, 838, CEP 85040-167 Guarapuava, PR, Brazil.
Int J Biol Macromol. 2021 Mar 1;172:133-142. doi: 10.1016/j.ijbiomac.2021.01.041. Epub 2021 Jan 12.
Ursolic acid (UA) is a naturally occurring triterpene that has been investigated for its antitumor activity. However, its lipophilic character hinders its oral bioavailability, and therapeutic application. To overcome these limitations, chitosan (CS) modified poly (lactic acid) (PLA) nanoparticles containing UA were developed, characterized, and had their oral bioavailability assessed. The nanoparticles were prepared by emulsion-solvent evaporation technique and presented a mean diameter of 330 nm, zeta potential of +28 mV, spherical shape and 90% encapsulation efficiency. The analysis of XRD and DSC demonstrated that the nanoencapsulation process induced to UA amorphization. The in vitro release assay demonstrated that 53% of UA was released by diffusion after 144 h, following a second-order release kinetics. In simulated gastrointestinal fluids and mucin interaction tests, CS played an important role in stability and mucoadhesiveness improvement of PLA nanoparticles, respectively. In the presence of erythrocytes, nanoparticles proved their hemocompatibility. In tumor cells, nanoparticles presented lower cytotoxicity than free UA, due to slow UA release. After a single oral dose in rats, CS modified PLA nanoparticles increased the UA absorption, reduced its clearance and elimination, resulting in increased bioavailability. The results show the potential application of these nanoparticles for UA oral delivery for cancer therapy.
熊果酸（UA）是一种天然存在的三萜，因其抗肿瘤活性而受到研究。然而，其亲脂性阻碍了其口服生物利用度和治疗应用。为了克服这些限制，开发了载有 UA 的壳聚糖（CS）修饰的聚乳酸（PLA）纳米粒，并对其进行了表征和口服生物利用度评估。纳米粒通过乳液溶剂蒸发技术制备，平均粒径为 330nm，zeta 电位为+28mV，呈球形，包封效率为 90%。XRD 和 DSC 的分析表明，纳米封装过程导致 UA 非晶化。体外释放试验表明，144 小时后扩散释放了 53%的 UA，遵循二级释放动力学。在模拟胃肠道液和粘蛋白相互作用试验中，CS 分别在稳定性和 PLA 纳米粒的粘弹性改善方面发挥了重要作用。在红细胞存在的情况下，纳米粒表现出良好的血液相容性。在肿瘤细胞中，由于 UA 缓慢释放，纳米粒的细胞毒性低于游离 UA。在大鼠单次口服给药后，CS 修饰的 PLA 纳米粒增加了 UA 的吸收，降低了其清除率和消除率，从而提高了生物利用度。结果表明，这些纳米粒具有用于癌症治疗的 UA 口服递药的潜力。
