Development and characterization of docetaxel-loaded lecithin-stabilized micellar drug delivery system (LsbMDDs) for improving the therapeutic efficacy and reducing systemic toxicity
Journal
European Journal of Pharmaceutics and Biopharmaceutics
Journal Volume
123
Pages
9-19
Date Issued
2018
Author(s)
Abstract
In the present study, we attempted to develop a lecithin-stabilized micellar drug delivery system (LsbMDDs) for loading docetaxel (DTX) to enhance its therapeutic efficacy and minimize systemic toxicity. A novel DTX-loaded LsbMDDs 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 LsbMDDs 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 LsbMDDs was slower than that from the generic product of DTX (Tynen?). A cell viability assay demonstrated that the LsbMDDs showed better cytotoxicity than Tynen? against CT26 cancer cells. The in vivo antitumor efficacy of the DTX-loaded LsbMDDs was observed to be better than that of Tynen? in a CT26 tumor-bearing mice model. A high-dose regimen of the DTX-loaded LsbMDDs 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 LsbMDDs, and its maximal tolerable doses for single and repeated injections were 2–2.5-fold higher than those of Tynen?. In conclusion, the LsbMDDs could be a promising high drug-loaded nanocarrier for delivering hydrophobic chemotherapeutic agents that can enhance the efficacy of chemotherapy and reduce systemic toxicity. ? 2017 Elsevier B.V.
Subjects
alpha tubulin; docetaxel; paclitaxel; phosphatidylcholine; antineoplastic agent; docetaxel; drug carrier; nanoparticle; phosphatidylcholine; taxoid; animal cell; animal experiment; antineoplastic activity; area under the curve; Article; cancer inhibition; cell viability; controlled study; depolymerization; drug cytotoxicity; drug delivery system; drug dose regimen; drug efficacy; drug megadose; drug release; drug stability; encapsulation; in vitro study; in vivo study; male; maximum tolerated dose; micelle; micellization; microtubule assembly; mouse; nonhuman; particle size; polymerization; prostate cancer; room temperature; single drug dose; therapy effect; transmission electron microscopy; tumor growth; tumor volume; tumor xenograft; weight change; weight reduction; animal; Bagg albino mouse; cell survival; chemistry; drug delivery system; drug effect; human; MCF-7 cell line; micelle; procedures; suspension; tumor cell line; Animals; Antineoplastic Agents; Cell Line, Tumor; Cell Survival; Drug Carriers; Drug Delivery Systems; Humans; Lecithins; Male; MCF-7 Cells; Mice; Mice, Inbred BALB C; Micelles; Nanoparticles; Particle Size; Suspensions; Taxoids
SDGs
Other Subjects
alpha tubulin; docetaxel; paclitaxel; phosphatidylcholine; antineoplastic agent; docetaxel; drug carrier; nanoparticle; phosphatidylcholine; taxoid; animal cell; animal experiment; antineoplastic activity; area under the curve; Article; cancer inhibition; cell viability; controlled study; depolymerization; drug cytotoxicity; drug delivery system; drug dose regimen; drug efficacy; drug megadose; drug release; drug stability; encapsulation; in vitro study; in vivo study; male; maximum tolerated dose; micelle; micellization; microtubule assembly; mouse; nonhuman; particle size; polymerization; prostate cancer; room temperature; single drug dose; therapy effect; transmission electron microscopy; tumor growth; tumor volume; tumor xenograft; weight change; weight reduction; animal; Bagg albino mouse; cell survival; chemistry; drug delivery system; drug effect; human; MCF-7 cell line; micelle; procedures; suspension; tumor cell line; Animals; Antineoplastic Agents; Cell Line, Tumor; Cell Survival; Drug Carriers; Drug Delivery Systems; Humans; Lecithins; Male; MCF-7 Cells; Mice; Mice, Inbred BALB C; Micelles; Nanoparticles; Particle Size; Suspensions; Taxoids
Type
journal article