Long circulating poly(ethylene glycol)-decorated lipid nanocapsules deliver docetaxel to solid tumors.
OBJECTIVE
The purpose of this study was to evaluate the ability of poly(ethylene glycol)-coated lipid nanocapsules (LN) to deliver the highly potent hydrophobic anticancer drug docetaxel to solid tumors.


METHODS
Docetaxel-loaded nanocapsules (80-120 nm) were produced by a solvent-free phase inversion process and were coated with polyethylene glycol distearoylphosphatidylethanolamine conjugate by a postinsertion step. In vivo studies were conducted in mice bearing subcutaneously implanted C26 colon adenocarcinoma to assess the pharmacokinetics and biodistribution of both the drug and LN.


RESULTS
Incorporation of docetaxel into the LN dramatically increased the drug's biological half-life while providing substantial accumulation at the tumoral site. The pharmacokinetics and biodistribution pattern were found to depend on the specific surface area and shell composition of the nanocapsules.


CONCLUSIONS
This study demonstrates that docetaxel physically entrapped into a lipid colloidal drug carrier can be efficiently targeted to neoplastic tissues.
Khalid
Mohamed Nabil
MN
Faculty of Pharmacy, University of Montreal, C.P. 6128 Succ, Centre-ville, Montreal, (QC), H3C 3J7, Canada.
Simard
Pierre
P
Hoarau
Didier
D
Dragomir
Alice
A
Leroux
Jean-Christophe
JC
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002214:Capsules; D045744:Cell Line, Tumor; D000077143:Docetaxel; D004337:Drug Carriers; D016503:Drug Delivery Systems; D005079:Excipients; D005260:Female; D006207:Half-Life; D006801:Humans; D008055:Lipids; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000378:metabolism*; D010316:Particle Size; D011092:Polyethylene Glycols; D043823:Taxoids / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D014018:Tissue Distribution
D000972:Antineoplastic Agents, Phytogenic; D002214:Capsules; D004337:Drug Carriers; D005079:Excipients; D008055:Lipids; D043823:Taxoids; D000077143:Docetaxel; D011092:Polyethylene Glycols