Development and characterization of docetaxel-loaded lecithin-stabilized micellar drug delivery system (L_sbMDDs) 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_sbMDDs) for loading docetaxel (DTX) to enhance its therapeutic efficacy and minimize systemic toxicity. A novel DTX-loaded L_sbMDDs was optimally prepared by a thin-film hydration method and then hydrated with a lecithin nanosuspension while being subjected to ultrasonication. Physical characteristics of the optimized DTX-loaded L_sbMDDs 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 °C being longer than 2 and 7 days, respectively. The in vitro release of DTX from the DTX-loaded L_sbMDDs was slower than that from the generic product of DTX (Tynen®). A cell viability assay demonstrated that the L_sbMDDs showed better cytotoxicity than Tynen® against CT26 cancer cells. The in vivo antitumor efficacy of the DTX-loaded L_sbMDDs was observed to be better than that of Tynen® in a CT26 tumor-bearing mice model. A high-dose regimen of the DTX-loaded L_sbMDDs formulation showed greater inhibition of DU145 tumor growth than did Tynen®, 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_sbMDDs, and its maximal tolerable doses for single and repeated injections were 2–2.5-fold higher than those of Tynen®. In conclusion, the L_sbMDDs could be a promising high drug-loaded nanocarrier for delivering hydrophobic chemotherapeutic agents that can enhance the efficacy of chemotherapy and reduce systemic toxicity.