Pegylated nanocapsules produced by an organic solvent-free method: Evaluation of their stealth properties.
OBJECTIVE
To develop from an original process, a novel generation of stealth lipidic nanocapsules in order to improve the lipophilic drug delivery in accessible sites.


METHODS
Nanocapsules covered by PEG1500 stearate were obtained by a low energy emulsification method. Conductivity measurements and ternary diagram were performed to describe the formulation mechanism. Hemolytic dosage CH50 and pharmacokinetic study in rats have been achieved in order to study the stealth properties of nanocapsules.


RESULTS
Transition from an O/W emulsion to a w/O/W emulsion was necessary to produce PEG1500 stearate nanocapsules. Interestingly nanocapsules with a size around 26 nm and a polydispersity index inferior to 0.1 were obtained. The CH50 test has revealed a very weak complement consumption in the presence of such nanocapsules. Moreover, after intravenous injection into rats, PEG1500 stearate nanocapsules exhibited long circulating properties. The experimental data support the concept of steric repulsion of the surface towards proteins, displayed by nanocapsules covered with PEG1500 stearate. These in vivo results were in agreement with the PEG1500 density calculated at the nanocarrier surface.


CONCLUSIONS
Injectable drug carriers have been developed. Their long-circulating properties could confer them a strong potential for lipophilic drug targeting.
Béduneau
Arnaud
A
Inserm U646, Université d'Angers, Angers F-49100, France.
Saulnier
Patrick
P
Anton
Nicolas
N
Hindré
François
F
Passirani
Catherine
C
Rajerison
Holisoa
H
Noiret
Nicolas
N
Benoit
Jean-Pierre
JP
D000465:Algorithms; D000818:Animals; D002214:Capsules; D004553:Electric Conductivity; D004563:Electrochemistry; D024202:Electrophoretic Mobility Shift Assay; D005079:Excipients; D007275:Injections, Intravenous; D008297:Male; D046529:Microscopy, Electron, Transmission; D010316:Particle Size; D010592:Pharmaceutic Aids; D011092:Polyethylene Glycols / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D012997:Solvents; D013535:Suspensions; D013667:Technetium / Q000493:pharmacokinetics; D015054:Zymosan / Q000737:chemistry
D002214:Capsules; D005079:Excipients; D010592:Pharmaceutic Aids; D012997:Solvents; D013535:Suspensions; D011092:Polyethylene Glycols; D013667:Technetium; D015054:Zymosan