Targeted Approach for Prostate Cancer Treatment: Synthesis and Characterization of Docetaxel-Loaded Perfluorocarbon Nanodroplets

Abstract

The purpose of this study is to synthesize and characterize nanodroplets, loaded with docetaxel for treatment of prostate cancer under MR-guided focused ultrasound. Water insoluble docetaxel encapsulated in nanodroplets is expected to be delivered into tumors with greater efficiency while minimizing drug related systemic toxicities when used in combination with focused ultrasound. The sequence of our studies toward development and characterization of docetaxel-loaded nanodroplets is as follows. First, we developed methods for synthesis of ultrasound-responsive, docetaxel-loaded nanodroplets (Doc-nd) by a solid dispersion technique. Secondly, we characterized Doc-nd by its morphology and size distributions using a dynamic light scattering (DLS) method. To check the consistency of the data obtained from DLS, size distribution was also studied using an independent technique by analyzing bright field microscopy images of Doc-nd in software ImageJ. Thirdly, we studied the encapsulation efficiency and the release kinetics of docetaxel from Doc-nd in phosphate buffer saline. Finally, we performed in vitro cytotoxicity studies using a human prostate cancer cell line (LNCaP). Our data showed that peak sizes of spherical Doc-nd were 222±15 nm. These sizes favor passive accumulation into most tumors thus potentially increasing localized docetaxel concentration. A high encapsulation efficiency of 93.70% was obtained for Doc-nD. The release kinetics studies showed that docetaxel was released from Doc-nd in a three- staged release pattern with an initial release of 30% in one hour followed by a 50% release until 12h and an 85% release after three days. In vitro cytotoxicity studies using LNCaP cells indicated a time-dependent cytotoxic profile and verified encapsulation of docetaxel in the nanodroplets. Our study suggested that Doc-nd may have the potential for treating prostate cancer with an improved therapeutic ratio when combined with MR-guided focused ultrasound.