Abstract:

Polymeric micelles have proven their ability to deliver poorly water-soluble anticancer drugs, improve drug stability, and have good penetration and site-specificity, leading to enhance therapeutic efficacy. As paclitaxel (PTX), an effective anticancer agent, has a very poor solubility in water the aim of this project is the development of a novel drug delivery system based on dual encapsulation of paclitaxel and ursolic acid in smart polymeric micelles, in order to overcome the poor solubility of paclitaxel, to attenuate chemoresistance and to increase its bioavailability and therapeutic efficacy, but also to reduce the chemotherapy-induced intestinal mucositis effects. The specific objectives are: design, development and characterization of a novel dual PTX-ursolic acid loaded smart polymeric micellar system (PTX-UA PMs); in vitro evaluation and in vivo validation of the anti-tumoral effects of the novel PTX-UA PMs against breast cancer. This is the first study which evaluates the effectiveness of the dual encapsulation of PTX and ursolic acid in smart polymeric micelles; the in vivo synergistic antitumor effect of PTX and ursolic acid, formulated in polymeric micelles; the alleviation of chemotherapy-induced mucositis by PTX with the addition of ursolic acid.