Remotely Rutin-Loaded into Liposomes for Efficient Encapsulation and Enhancement of Bioavailability and Brain Targeting in vivo

Background and Objective: Rutin exerts a potential application in brain diseases, but it is difficult to cross the blood-brain barrier (BBB) and its bioavailability is limited. A biocompatible liposome system of rutin using a remote loading strategy had developed by us. The present work aimed to evaluate its characteristics, bioavailability and brain targeting in vivo. Materials and Methods: Rutin liposome (rutin-lipo) was prepared by calcium acetate gradient combined with reverse evaporation method. Subsequently, the encapsulation efficiency (EE) of rutin was measured using centrifugal ultrafiltration, size distribution, zeta-potential and state of rutin were determined by laser particle size analyze and Fourier transform infrared spectrum (FT-IR), respectively. Moreover, drug release in vitro was evaluated by the dialysis method. After the methodology of HPLC was evaluated for detecting drug concentration in plasma and different tissues of mice, pharmacokinetic and biodistribution were measured. Furthermore, the relative uptake rate (Re) and peak concentration ratio (Ce) were calculated to assess the targeting performance of rutin-lipo. Results: The EE of rutin, average size and zeta-potential were 80.05 +/- 3.04%, 149.3 +/- 7.7 nm and -4.1 +/- 0.8 mV, respectively. The FT-IR revealed that rutin was effectively loaded into the liposomes and rutin-lipo possessed a higher cumulative drug release percentage than rutin. Moreover, rutin presents enterohepatic circulation and all pharmacokinetics parameters of rutin-lipo better than those of the solubilized rutin, including half-life of elimination (t(1/2(beta))), mean residence time (MRT), clearance rate (CL) and relative bioavailability (220.76%). Furthermore, the drug distribution of rutin-lipo was the most changed in the liver due to its Ce (2.9236) being the largest. Notably, the brain Re of rutin-lipo was 2.6429 although its Ce was 0.9629. Conclusion: Rutin-lipo significantly increased the bioavailability of rutin via enterohepatic circulation and had the brain targeting, thus, providing an attractive alternative for applications of rutin in brain diseases.