Novel long-circulating lipid nanocapsules.
OBJECTIVE
To develop and evaluate novel long-circulating lipid nanocapsules (LN) designed for tumor delivery of lipophilic drugs.


METHODS
Nanocapsules were produced by a solvent-free phase inversion process and were coated with polyethylene glycoldistearoylphosphatidylethanolamine conjugate (DSPE-PEG) during preparation or by a post-insertion step. In vivo studies were conducted in rats to assess LN pharmacokinetics and biodistribution.


RESULTS
Post-insertion of DSPE-PEG appeared to be a convenient and effective method of obtaining LN of controlled sizes with high PEG density at their surface. After intravenous injection to rats, PEGylated lipid nanocapsules obtained by the post-insertion method exhibited long-circulating properties. Up to 50% of the injected dose was still present in the blood 8 h after administration for LN containing 6 mol% PEG 5000 or 10 mol% PEG 2000. This represented an area under the blood concentration-time curve of almost 70% that of liposomes used in the Doxil formulation.


CONCLUSIONS
With a simple solvent free-process, it was possible to produce long-circulating LN of controlled sizes. Such LN could prove useful for the passive delivery of lipophilic anticancer drugs to solid tumors.
Hoarau
Didier
D
Canada Research Chair in Drug Delivery, Faculty of Pharmacy, University of Montreal, C.P. 6128 Succ. Centre-ville, Montreal (Qc) Canada H3C 3J7.
Delmas
Pascal
P
David
Stéphanie
S
Roux
Emmanuelle
E
Leroux
Jean-Christophe
JC
D000465:Algorithms; D000818:Animals; D019540:Area Under Curve; D002214:Capsules / Q000493:pharmacokinetics; D007275:Injections, Intravenous; D008055:Lipids / Q000737:chemistry; D008081:Liposomes; D008297:Male; D018625:Microscopy, Atomic Force; D010316:Particle Size; D010714:Phosphatidylethanolamines; D011092:Polyethylene Glycols / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
D002214:Capsules; D008055:Lipids; D008081:Liposomes; D010714:Phosphatidylethanolamines; C038089:1,2-distearoylphosphatidylethanolamine; D011092:Polyethylene Glycols