Efficient delivery of ursolic acid by poly(N-vinylpyrrolidone)-block-poly (ε-caprolactone) nanoparticles for inhibiting the growth of hepatocellular carcinoma in vitro and in vivo

Abstract

Hao Zhang,1,* Donghui Zheng,2,* Jing Ding,3 Huae Xu,4 Xiaolin Li,1 Weihao Sun11Department of Geriatric Gastroenterology, First Affiliated Hospital with Nanjing Medical University, Nanjing, People’s Republic of China; 2Department of Nephrology, Huai’an Hospital Affiliated with Xuzhou Medical College and Huai’an Second Hospital, Huai’an, People’s Republic of China; 3Department of Respiratory Medicine, Affiliated Nanjing Children Hospital with Nanjing Medical University, 4Department of Pharmacy, First Affiliated Hospital with Nanjing Medical University, Nanjing, People’s Republic of China*These authors contributed equally to this article Abstract: Previous reports have shown that ursolic acid (UA), a pentacyclic triterpenoid derived from Catharanthus trichophyllus roots, could inhibit the growth of a series of cancer cells. However, the potential for clinical application of UA is greatly hampered by its poor solubility, whereas the hydrophobicity of UA renders it a promising model drug for nanosized delivery systems. In the current study, we loaded UA into amphiphilic poly(N-vinylpyrrolidone)-block-poly (ε-caprolactone) nanoparticles and performed physiochemical characterization as well as analysis of the releasing capacity. In vitro experiments indicated that UA-NPs inhibited the growth of liver cancer cells and induced cellular apoptosis more efficiently than did free UA. Moreover, UA-NPs significantly delayed tumor growth and localized to the tumor site when compared with the equivalent dose of UA. In addition, both western blotting and immunohistochemistry suggested that the possible mechanism of the superior efficiency of UA-NPs is mediation by the regulation of apoptosis-related proteins. Therefore, UA-NPs show potential as a promising nanosized drug system for liver cancer therapy. Keywords: apoptosis, liver cancer, drug delivery, antitumor