Development and characterization of docetaxel-loaded lecithin-stabilized micellar drug delivery system (LsbMDDs) for improving the therapeutic efficacy and reducing systemic toxicity

In the present study, we attempted to develop a lecithin-stabilized micellar drug delivery system (L(sb)MDDs) for loading docetaxel (DTX) to enhance its therapeutic efficacy and minimize systemic toxicity. A novel DTX-loaded L(sb)MDDs was optimally prepared by a thin-film hydration method and then hydrated with a lecithin nanosus-pension while being subjected to ultrasonication. Physical characteristics of the optimized DTX-loaded L(sb)MDDs formulations were examined and found to have a mean size of < 200 nm, an encapsulation efficiency of > 90%, and drug loading of > 6% with stability at room temperature and at 4 degrees C being longer than 2 and 7 days, respectively. The in vitro release of DTX from the DTX-loaded L(sb)MDDs was slower than that from the generic product of DTX (Tynen (R)). A cell viability assay demonstrated that the L(sb)MDDs showed better cytotoxicity than Tynen((R)) against CT26 cancer cells. The in vivo antitumor efficacy of the DTX-loaded L(sb)MDDs was observed to be better than that of Tynen (R) in a CT26 tumor-bearing mice model. A high-dose regimen of the DTX-loaded L(sb)MDDs formulation showed greater inhibition of DU145 tumor growth than did Tynen((R)) but with less to similar systemic toxicity. An in vivo study also showed that a greater amount of drug was able to accumulate in the tumor site with the DTX-loaded L(sb)MDDs, and its maximal tolerable doses for single and repeated injections were 2-2.5-fold higher than those of Tynen((R)) In conclusion, the L(sb)MDDs could be a promising high drug-loaded nanocarrier for delivering hydrophobic chemotherapeutic agents that can enhance the efficacy of chemotherapy and reduce systemic toxicity.