Novel amphiphilic hydroxyethyl starch-based nanoparticles loading camptothecin exhibit high anticancer activity in HepG2 cells and zebrafish.

ABSTRACT

Camptothecin is a naturally occurred anticancer drug but exhibits limitations including poor aqueous solubility, low bioavailability, and high level of adverse drug reactions on normal organs. To overcome these problems, this paper developed a novel amphiphilic Lau-Leu-HES carrier using hydroxyethyl starch, lauric acid, and L-leucine as starting materials. The carrier was successfully applied to prepare Lau-Leu-HES nanoparticles loading camptothecin. The drug loading efficiency and encapsulation efficiency of the nanoparticles were calculated to be 29.04% and 81.85%, respectively. The nanoparticles exhibited high zeta potential (-15.51 mV) and small hydrodynamic diameter (105.4 nm). Camptothecin in nanoparticles could be rapidly released under acidic condition (pH = 4.5), thereby indicating the high sensitivity under cancer microenvironments. Anticancer investigation revealed that the nanoparticles could inhibit the proliferation of HepG2 cells in vitro. Compared with commercial available drug doxorubicin, the nanoparticles could significantly inhibit the expression of krasv12 oncogene in transgenic Tg (EGFP-krasV12) zebrafish. These results indicate that the camptothecin-loaded Lau-Leu-HES nanoparticles are expected to be a potential candidate for cancer therapy.