Preparation and pharmacokinetics of docetaxel based on nanostructured lipid carriers.
OBJECTIVE
This study describes the preparation and pharmacokinetics of docetaxel based on freeze-dried nanostructured lipid carriers (NLCs).


METHODS
The docetaxel-incorporated NLCs were developed using hot high-pressure homogenisation, and lyophilised to obtain freeze-dried docetaxel NLCs. The influences of different concentrations of lipid matrices, ratio of drug to lipid, and different cryoprotectants on the characteristics of the NLCs were investigated.


RESULTS
Freeze-dried docetaxel NLCs were spherical, with 5% (w/w) docetaxel loading efficiency and were stable for at least 6 months at 25 masculineC. X-ray powder diffraction and differential scanning calorimetry analysis suggested that docetaxel was distributed in a molecular or amorphous status. In-vitro release studies showed sustained drug release, with the cumulated release rate of 13% within 24 h without burst release. The freeze-dried docetaxel NLCs also showed sustained-release properties after intravenous injection into rats. The area under the plasma-concentration time curve and mean residence time were increased 4.90 and 2.82 times compared with docetaxel solution. The concentration of docetaxel in the lungs was significantly higher in rats treated with the NLCs than in those given docetaxel solution.


CONCLUSIONS
Docetaxel NLCs have an organ-targeting effect and prolonged mean retention time and have potential for the treatment of lung cancer.
Li
Xiang
X
Department of Pharmaceutics, Shenyang Pharmaceutical University, Shenyang, People's Republic of China.
Wang
Dongkai
D
Zhang
Jing
J
Pan
Weisan
W
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002152:Calorimetry, Differential Scanning; D003692:Delayed-Action Preparations / Q000737:chemistry / Q000592:standards; D000077143:Docetaxel; D004337:Drug Carriers / Q000737:chemistry / Q000592:standards*; D004339:Drug Compounding; D004355:Drug Stability; D005612:Freeze Drying; D008055:Lipids / Q000737:chemistry* / Q000493:pharmacokinetics; D008168:Lung / Q000378:metabolism; D008297:Male; D049329:Nanostructures; D009928:Organ Specificity; D051381:Rats; D017208:Rats, Wistar; D043823:Taxoids / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics
D000972:Antineoplastic Agents, Phytogenic; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D008055:Lipids; D043823:Taxoids; D000077143:Docetaxel