PURPOSE: To develop from an original process, a novel generation of stealth lipidic nanocapsules in order to improve the lipophilic drug delivery in accessible sites. MATERIALS AND 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.
PURPOSE: To develop from an original process, a novel generation of stealth lipidic nanocapsules in order to improve the lipophilic drug delivery in accessible sites. MATERIALS AND 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.
Authors: Hartwig Meyer; Timo Stöver; Florian Fouchet; Guillaume Bastiat; Patrick Saulnier; Wolfgang Bäumer; Thomas Lenarz; Verena Scheper Journal: Int J Nanomedicine Date: 2012-05-15