Abstract 5658: Development and optimization of CZ48-loaded microbubbles for controlled drug delivery .

CZ48, the 20-O-propionate ester of camptothecin, is a prodrug requiring activation by converting to parental CPT in vivo. To circumvent the problems of low water solubility, lack of absorption, and poor bioavailability, novel CZ48-loaded microbubbles were investigated in this study. CZ48-loaded microbubbles were prepared at particle sizes ranging from 0.5 μm to 6.7 μm using a double emulsion technique (W/O/W). The satisfactory encapsulation efficiency and drug-loading content were 85.73±2.41% and 26.07±0.76%, respectively. The successful encapsulation of the microbubbles was confirmed by confocal laser scanning microscope (CLSM) observations and X-ray diffraction (XRD) patterns. The comparison between the controlled drug release from CZ48-loaded microbubbles and the free drug release from plain CZ48 crystals was performed in vitro, showing that 55% of the CZ48 was steadily released by the CZ48-loaded microbubbles in the first 48 hrs while more than 90% of the CZ48 was rapidly released by CZ48 crystals within the first 5 hrs. In vivo pharmacokinetic studies indicated that the bioavailabilities of CZ48 and CPT from CZ48-loaded microbubbles raised 121% and 517%, respectively, after intravenous administration compared to the plain CZ48. Compared to the plain CZ48, CZ48-loaded microbubbles also showed a higher mean residence time (MRT) and a longer elimination half-life (T1/2), indicating that CZ48-loaded microbubbles were indeed able to release CZ48 drug in a finely controlled manner. These results demonstrated that such microbubbles could be a promising approach for the construction of an effectively controlled drug delivery system for CZ48 as well as for other drugs with lower water solubility. Citation Format: Yang Wang, Siyang Li, Jian Zheng, Xiufeng Yan, Zhisong Cao, Dana Vardeman, Beppino Giovanella. Development and optimization of CZ48-loaded microbubbles for controlled drug delivery . [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5658. doi:10.1158/1538-7445.AM2013-5658