Conception, développement et optimisation des Nanoparticules lipidiques solides contenant du Temozolomide comme agent anticancéreux

Solid Lipid Nanoparticles loaded Temozolomide were prepared by simple hot nanoemulsion method and evaluated for their in vitro drug release profile. Glyceryl Monostearate was used as lipid core; Tween 80 and Pluronic F-68 as surfactant and cosurfactant. The preformulation studies (FT-IR and DSC) revealed that the excipients used are compatibles to the drug. Four formulation parameters were optimized to obtain high quality nanoparticles. The physicochemical properties of the TMZD-SLNs were investigated by particle size analysis, zeta potential measurement, drug entrapment efficiency (EE), stability and in vitro release behavior. There was no significant change in term of physicochemical properties and drug release profile between predicted and actual values. The TMZD-SLNs showed stable size distribution at 151.4 nm with Z-potential of -24.2 mV, ideal drug EE (58.14±0.44%) and relative long term physical stability after being stored for 3 months. The drug release of TMZD-SLNs up to 24 hours exhibited a sustained profile compared to its release from Temozolomide aqueous solution which made it a promising carrier for oral sustained release drug delivery systems. Kinetic of drug release from optimized formulation was found to be zero order (time independent). It also showed almost linear regression in Higuchi’s plot which confirms that diffusion is one of the mechanisms for drug release. In conclusion, this study showed that it was possible to obtain by this method Temozolomide solid lipid nanoparticles with small particle size and ideal EE and finally obtain the sustained release of the drug, meanwhile avoiding adverse side effects by the conventional formulation