Long circulating lipid nanocapsules for drug detoxification.
Uncoated and poly(ethylene glycol) (PEG)-decorated lipid nanocapsules (NC) prepared from medium chain triglycerides were investigated both in vitro and in vivo as parenteral detoxifying colloids for their ability to sequester haloperidol, docetaxel and paclitaxel. In vitro studies showed that the uptake depended on the nature of the drug and the composition of NC core and shell. In the case of haloperidol, maximal affinity was achieved upon incorporation of a complexing fatty acid. In plasma lipoprotein distribution studies, the association of both haloperidol and docetaxel into triglyceride-rich lipoprotein fraction was significantly increased in the presence of NC. The ability of the NC to lower the free drug concentrations in incubation medium was confirmed by cytotoxicity studies, where the antiproliferative activity of docetaxel was significantly decreased in the presence of NC. Using docetaxel as drug model, the NC were finally evaluated for their uptake potential in mice by one of the following administration sequences between the drug solution (Taxotere, DTX) and NC: NC-DTX, PEG(NC)-DTX and DTX-PEG(NC). Irrespective of the administration sequence, the NC increased the blood levels of docetaxel due to the in situ sequestration of drug by the circulating carrier. These findings suggest that lipid NC could be used as a non-specific mode to deal with the sequestration of molecules with high affinity for oils.
Dhanikula
Anand Babu
AB
Canada Research Chair in Drug Delivery, Faculty of Pharmacy, C.P. 6128 Succ. Centre-ville, Montreal, QC, Canada H3C 3J7.
Khalid
Nabil Mohamed
NM
Lee
Stephen D
SD
Yeung
Rosanna
R
Risovic
Verica
V
Wasan
Kishor M
KM
Leroux
Jean-Christophe
JC
D000818:Animals; D002214:Capsules / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D004058:Diffusion; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D008658:Inactivation, Metabolic / Q000502:physiology; D008055:Lipids / Q000737:chemistry*; D008297:Male; D008657:Metabolic Clearance Rate; D051379:Mice; D049329:Nanostructures / Q000737:chemistry*; D009928:Organ Specificity; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000097:blood*; D010599:Pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
D002214:Capsules; D004337:Drug Carriers; D008055:Lipids; D004364:Pharmaceutical Preparations