Dual stimuli-responsive ursolic acid-embedded nanophytoliposome for targeted antitumor therapy

• Published in: International journal of pharmaceutics 2020-05, Vol.582, p.119330, Article 119330
• Main Authors: Poudel, Kishwor, Gautam, Milan, Maharjan, Srijan, Jeong, Jee-Heon, Choi, Han-Gon, Khan, Gulam Muhammad, Yong, Chul Soon, Kim, Jong Oh
• Format: Article
• Language: English
• Subjects: Animals; Anticancer effect; Antineoplastic Agents, Phytogenic - chemistry; Antineoplastic Agents, Phytogenic - metabolism; Antineoplastic Agents, Phytogenic - pharmacology; Apoptosis - drug effects; Cell Line, Tumor; Cell Proliferation - drug effects; Drug Compounding; Drug Liberation; Female; Humans; Hyaluronan Receptors - metabolism; Hyaluronic Acid - chemistry; Liposomes; Mice, Inbred BALB C; Mice, Nude; Nanoparticles; Nanophytoliposome; Nanosystem; Neoplasms - drug therapy; Neoplasms - metabolism; Neoplasms - pathology; Polylysine - chemistry; Stimuli Responsive Polymers - chemistry; Stimuli responsiveness; Tissue Distribution; Triterpenes - chemistry; Triterpenes - metabolism; Triterpenes - pharmacology; Ursolic Acid
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2020.119330

[Display omitted] •Ursolic acid-loaded nanophytoliposomes were fabricated.•Phytosomes showed enhanced permeation and retention and active targeting.•Phytosomes showed high antitumor effect in in vitro and in vivo assessments. The hindrances in achieving clinically translatable anticancer platforms are being tackled through nanotechnology-based formulations. In this study, stimuli-responsive, phytoactive constituent-loaded nanophytoliposomes were fabricated for designing a specific antitumor platform. Ursolic acid (UA)-loaded nanophytoliposomes (UA-PLL-HA.P) enwrapped in a poly-L-lysine (PLL) coat and hyaluronic acid (HA) were nanosized; these nanophytoliposomes had spherical morphology, slightly negative charge, and an in-range polydispersity index (~0.25). Successful fabrication of the nanosystem was proven through several characterization methods and the pH- and enzyme-responsiveness of the nanosystem was assessed through a release study. The cellular internalization in CD44 receptor-expressing cell lines was amplified by enhanced permeation and retention as well as by active targeting. In vitro antitumor behavior was confirmed through in vitro cytotoxic and apoptotic activity of the nanosystem. Similarly, in vivo imaging showed exceptional biodistribution in the tumor in agreement with the in vitro findings. Moreover, the tumor inhibitory rate of UA-PLL-HA.P was significantly higher, and was ascribed to the targeting potential and stimuli-responsiveness. In summary, UA-PLL-HA.P exhibited pronounced anticancer effect and could open a number of possibilities for discovering novel phytoconstituent-incorporated nanoformulations.