Preparation, Characterization and Anti-Glioma Effects of Docetaxel-Incorporated Albumin-Lipid Nanoparticles

Poor aqueous solubility is a serious problem for most chemotherapeutics. Docetaxel (DTX), an inhibitor of microtubule depolymerization, is frequently used to treat many malignancies. However, the surfactant used in its commercial preparation (Taxotere^®) has proven problematic in clinical use because it has been associated with several side effects. By utilizing the high DTX-loading property of albumin, a new formulation, DTX-incorporated albumin-lipid nanoparticles (DNPs), was prepared and evaluated. DTX was bound to albumin in vitro and dispersed by egg yolk lecithin. The DNP particle size was 110.1 nm, while the average DNP zeta potential was –2.95 mV. The median lethal dose of DNPs was 180.6 mg/kg, which was 75.3% higher than that of Taxotere^®. DNPs could effectively inhibit the proliferation of several cell lines and induce cell apoptosis. In vivo imaging suggested that DNPs localize to and accumulate at the glioma site, which is likely due to the enhanced permeation and retention effects of DNPs. These pharmacological experiments further confirmed that DNPs can inhibit tumor growth, prolong the median survival time of mice with gliomas and induce higher levels of apoptosis. In conclusion, this novel formulation of DTX (DNPs) displayed lower toxicity and a superior anti-glioma effect relative to standard DTX preparations.