Abriata Juliana Palma, Eloy Josimar O, Riul Thalita Bachelli, Campos Patricia Mazureki, Baruffi Marcelo Dias, Marchetti Juliana Maldonado
School of Pharmaceutical Sciences of Ribeirao Preto, University of Sao Paulo, Brazil.
School of Pharmaceutical Sciences of Ribeirao Preto, University of Sao Paulo, Brazil.
Mater Sci Eng C Mater Biol Appl. 2017 Aug 1;77:1196-1203. doi: 10.1016/j.msec.2017.03.266. Epub 2017 Mar 31.
Despite affecting millions of people worldwide, Chagas disease is still neglected by the academia and industry and the therapeutic option available, benznidazole, presents limited efficacy and side effects. Within this context, ursolic acid may serve as an option for treatment, however has low bioavailability, which can be enhanced through the encapsulation in polymeric nanoparticles. Therefore, herein we developed ursolic acid-loaded nanoparticles with poly-ε-caprolactone by the nanoprecipitation method and characterized them for particle size, zeta potential, polydispersity, encapsulation efficiency, morphology by scanning electron microscopy and thermal behavior by differential scanning calorimetry. Results indicated that an appropriate ratio of organic phase/aqueous phase and polymer/drug is necessary to produce smaller particles, with low polydispersity, negative zeta potential and high drug encapsulation efficiency. In vitro studies indicated the safety of the formulation against fibroblast culture and its efficacy in killing T. cruzi. Very importantly, the in vivo study revealed that the ursolic acid-loaded nanoparticle is as potent as the benznidazole group to control parasitemia, which could be attributed to improved bioavailability of the encapsulated drug. Finally, the toxicity evaluation showed that while benznidazole group caused liver toxicity, the nanoparticles were safe, indicating that this formulation is promising for future evaluation.
尽管恰加斯病在全球影响着数百万人，但该疾病仍然被学术界和产业界所忽视，而且现有的治疗药物苯硝唑疗效有限且有副作用。在此背景下，熊果酸可能成为一种治疗选择，然而其生物利用度较低，可通过封装在聚合物纳米颗粒中来提高。因此，我们在此采用纳米沉淀法制备了载有熊果酸的聚ε-己内酯纳米颗粒，并对其粒径、zeta电位、多分散性、包封率、通过扫描电子显微镜观察的形态以及通过差示扫描量热法观察的热行为进行了表征。结果表明，有机相/水相以及聚合物/药物的适当比例对于制备更小的颗粒是必要的，这些颗粒具有低多分散性、负zeta电位和高药物包封率。体外研究表明该制剂对成纤维细胞培养物具有安全性，并且在杀死克氏锥虫方面具有有效性。非常重要的是，体内研究表明载有熊果酸的纳米颗粒在控制寄生虫血症方面与苯硝唑组一样有效，这可能归因于封装药物的生物利用度提高。最后，毒性评估表明，虽然苯硝唑组导致肝脏毒性，但纳米颗粒是安全的，这表明该制剂有望用于未来的评估。
