The Effect of Surfactant on Paclitaxel Nanocrystals: An In Vitro and In Vivo Study.
In this study, we first investigated the change of the morphology of paclitaxel (PTX) nanocrystals by varying the type of stabilizer and increasing the amount of D-a-tocopheryl polyethylene glycol 1000 succinate (TPGS) in PTX/TPGS nanocrystals. Rod-shaped nanocrystals changed into relatively thermally stable spherical micelles as the amount of TPGS increased to 1/20 (PTX/TPGS). With these increasing amounts of TPGS, higher cytotoxicity and cellular uptake were observed in P-glycoprotein-overexpressing PTX-resistant (H460/TaxR) cancer cells. Compared to Taxol, PTX/Pluronic F127 (F127) (1/5) nanocrystals, PTX/TPGS (1/5) nanocrystals and PTX/TPGS (1/40) micelles showed significantly sustained in vitro release profiles. Pharmacokinetic studies showed that PTX from these nanoformulations was cleared more rapidly than PTX from Taxol after intravenous administration. However, although presenting an unfavorable pharmacokinetic profile, the biodistribution study showed that PTX/TPGS (1/40) micelles were more effective in promoting accumulation of PTX in drug resistant tumors than Taxol, due to the P-gp inhibition effect of TPGS.
Hongzhuo
H
Liu
Yan
Y
Ma
Dan
D
Liu
John K
JK
Fallon
Feng
F
Liu
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D048429:Cell Size; D004058:Diffusion; D005260:Female; D008657:Metabolic Clearance Rate; D051379:Mice; D008810:Mice, Inbred C57BL; D053769:Nanocapsules / Q000008:administration & dosage / Q000737:chemistry* / Q000648:ultrastructure; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D009928:Organ Specificity; D017239:Paclitaxel / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D011092:Polyethylene Glycols / Q000737:chemistry; D013501:Surface-Active Agents / Q000737:chemistry; D014018:Tissue Distribution; D016896:Treatment Outcome; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000737:chemistry
D000972:Antineoplastic Agents, Phytogenic; D053769:Nanocapsules; D013501:Surface-Active Agents; D014810:Vitamin E; D011092:Polyethylene Glycols; C014225:tocophersolan; D017239:Paclitaxel