Optimization of Nanostructured Lipid Carriers of Fenofibrate Using a Box-Behnken Design for Oral Bioavailability Enhancement.

BACKGROUND: Fenofibrate (FNB) is a commonly used hypolipidemic agent. However, the oral bioavailability of FNB is limited by slow dissolution due to its low solubility. Thus, investigations on novel FNB formulations are necessary for their use. OBJECTIVE: The objective of this study is to enhance the oral bioavailability of FNB using optimized Nanostructured Lipid Carrier (NLC) formulations. METHODS: Hot homogenization followed by ultrasonication was used to prepare FNB-NLCs. These formulations were optimized using a Box-Behnken design, where the amount of FNB (X1), a ratio of solid lipid/liquid lipid (X2), and the percentage of emulsifier (X3) were set as independent variables, while the particle size (Y1), and Entrapment Efficiency (EE%) (Y2), were used as dependent factors. An in vitro dissolution test was then performed using a paddle method, while an in vivo pharmacokinetic study of FNB-NLC formulation was performed in rats. RESULTS: FNB-NLCs were successfully prepared and optimized using a Box-Behnken design. The particle size and EE% of the FNB-NLC had less than 5% difference from predicted values. The in vitro dissolution and oral bioavailability of the FNB-NLC were both higher than those of raw FNB. CONCLUSION: A Box-Behnken design was successfully applied to optimize FNB-NLC formulation for the enhancement of the dissolution and bioavailability of FNB, a poorly water-soluble drug.

Red blood cell-hitchhiking chitosan nanoparticles for prolonged blood circulation time of vitamin K1.

Nanocarriers have been extensively applied for intravascular drug delivery. However, rapid clearance from circulation by mononuclear phagocyte system has limited their applications. Erythrocytes carriers are potential solutions to overcome the limitations of nanocarriers and considered to be ideal natural carriers for drug delivery because of their unique properties. The purpose of this work is to combine nanocarriers with erythrocytes carriers for sustained release and prolonged circulation time of vitamin K1. Chitosan nanoparticles loading VK1 (VK-CSNPs) were prepared using ionotropic gelation method, which was optimized using box-behnken design and response surface methodology. VK-CSNPs adsorbed onto red blood cells (RBC-VK-CSNPs) rapidly via electrostatic interactions. The exposure of phosphatidylserine, osmotic fragility and turbulence fragility of RBC loading nanoparticles were investigated to study the toxicity of nanoparticles to erythrocytes. In vivo pharmacokinetic study indicated that Cmax, AUC and MRT of RBC-VK-CSNPs group were remarkably higher than that of VK-CSNPs group. Flow cytometry showed VK-CSNPs steadily retained on the surface of RBC for a long time without affecting the circulation profiles of RBC themselves. The nanoparticles carried on RBC released drug, desorbed and were eliminated in vivo. Therefore, the circulation time of RBC-hitchhiking chitosan nanoparticles was greatly prolonged compared with nanoparticles alone. RBC-hitchhiking could be a valuable hybrid strategy for prolonging the in vivo life of nanocarriers.