Pharmacokinetics and tissue distribution of docetaxel by liquid chromatography-mass spectrometry: evaluation of folate receptor-targeting amphiphilic copolymer modified nanostructured lipid carrier.
A novel amphiphilic copolymer, folate-poly(PEG-cyanoacrylate-co-cholesteryl cyanoacrylate) (FA-PEG-PCHL) was synthesized to modify docetaxel-loaded nanostructured lipid carrier to lead to a long blood circulating effect and targeting ability for the delivery of antitumor drug in cancer. To investigate the characteristics of modified docetaxel-loaded nanostructured lipid carrier in vivo, a liquid chromatography-mass spectrometry method was developed and validated for the determination of docetaxel in rat plasma and tumor-bearing mouse tissue samples. The biosamples were extracted by liquid-liquid extraction method with ether and separated on a C(18) column (150 mm×4.6 mm, 5 μm) using a mobile phase consisting of methanol-0.01% formic acid water (82:18, v/v). The standard curves were linear over the ranges of 0.01-4.0 μg/mL for plasma and 0.02-8.0 μg/g for tissue samples, respectively. The validated method was successfully applied to the pharmacokinetic study in rat plasma and tissue distribution study in mouse tissues of docetaxel after an intravenous administration of docetaxel injection (DTX injection), docetaxel-loaded nanostructured lipid carrier (DTX-NLC) and FA-PEG-PCHL-modified docetaxel-loaded nanostructured lipid carrier (FA-DTX-NLC), respectively. The results indicated that the FA-DTX-NLC led to significant differences in pharmacokinetic profile and tissue distribution. Nanostructured lipid carrier modified by FA-PEG-PCHL could be one of the promising suspensions for the delivery of docetaxel in cancer.
School of Pharmacy, Shenyang Pharmaceutical University, Shenhe District, PR China.
Xu
X
Zhao
Yunli
Y
Zhao
Lulu
L
Geng
Xiang
X
Li
Xiaofan
X
Wang
Zhenzhen
Z
Liu
Dongkai
D
Wang
Kaishun
K
Bi
Xiaohui
X
Chen
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000032:analysis / Q000097:blood / Q000493:pharmacokinetics; D002788:Cholesterol Esters / Q000008:administration & dosage / Q000737:chemistry; D002853:Chromatography, Liquid / Q000379:methods*; D003487:Cyanoacrylates / Q000008:administration & dosage / Q000737:chemistry; D000077143:Docetaxel; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D004355:Drug Stability; D058972:Folic Acid Transporters / Q000737:chemistry / Q000378:metabolism*; D016014:Linear Models; D059625:Liquid-Liquid Extraction; D008297:Male; D013058:Mass Spectrometry / Q000379:methods*; D051379:Mice; D049329:Nanostructures; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000378:metabolism; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D043823:Taxoids / Q000008:administration & dosage / Q000032:analysis / Q000097:blood / Q000493:pharmacokinetics*; D014018:Tissue Distribution
D000970:Antineoplastic Agents; D002788:Cholesterol Esters; D003487:Cyanoacrylates; D004337:Drug Carriers; D058972:Folic Acid Transporters; D043823:Taxoids; D000077143:Docetaxel; D011092:Polyethylene Glycols