Formulation of acyclovir-loaded solid lipid nanoparticles: 2. Brain targeting and pharmacokinetic study

Acyclovir (ACV) is widely used in the treatment of herpes encephalitis. The present study was conducted to prepare chitosan-tween 80 coated solid lipid nanoparticles (SLNs) as a delivery system for brain targeting of ACV in rabbits. The SLNs were prepared and coated in one step by microemulsion method using a coating solution containing chitosan (0.1% w/v) and tween 80 (2% w/v) for loading sustained release ACV. In vitro characterization was performed for coated ACV-SLNs. Concerning in vivo experiments; a single intravenous bolus dose of coated ACV-SLNs was given versus free ACV solution to rabbits (62 mg/kg). Plasma pharmacokinetic parameters were calculated from the ACV concentration-time profiles in plasma using the two compartmental analysis. The values of AUC0−∞ and MRT of coated ACV-SLNs were higher than free drug by about twofold, 233.36 ± 41.56 μg.h/mL and 1.81 ± 0.36 h, respectively. The noncompartmental analysis was conducted to estimate the brain pharmacokinetic parameters. The AUC0−∞ brain/AUC0−∞ plasma ratio for coated ACV-SLNs and free ACV was 0.22 and 0.12, respectively. These results indicated the effectiveness of using coated ACV-SLNs for brain targeting.