Fabrication and characterization of TPGS-modified chlorogenic acid liposomes and its bioavailability in rats

Abstract

Chlorogenic acid (CGA), a polyphenol compound, exhibits excellent anti-oxidative, anti-hypoxic, antibacterial, antiviral, and anti-inflammatory activities, however the bioactivity of it has not been fully utilized in vivo due to its instability and low bioavailability. To address these issues, we prepared and characterized CGA-TPGS-LP, which is a TPGS-modified liposome loaded with CGA. The pharmacokinetics of CGA-TPGS-LP were studied in rats after oral administration. CGA-TPGS-LP was fabricated using a combination of thin film dispersion and ion-driven methods. The liposomes were observed to be uniformly small and spherical in shape. Their membranes were composed of lecithin, cholesterol, and TPGS lipophilic head with a TPGS hydrophilic tail chain coating on its surface. The loading efficiency and encapsulation efficiency were found to be 11.21% and 83.22%, respectively. The physicochemical characterisation demonstrated that the CGA was present in an amorphous form and retained its original structural state within the liposomal formulation. The stability of CGA was significantly improved by fabricating TPGS-LP. CGA-TPGS-LP exhibited good sustained-release properties in both simulated gastric and intestinal fluids. Following oral administration, ten metabolites were identified in rat plasma using UPLC-QTOF-MS. UPLC-QqQ-MS/MS quantitative analysis demonstrated that the oral bioavailability of CGA encapsulated in TPGS-modified liposomes was enhanced by 1.52 times. In addition, the three main metabolites of CGA had higher plasma concentrations and slower degradation rate. These results demonstrate that TPGS-modified liposomes could be a feasible strategy to further enhance the oral bioavailability of CGA, facilitating its clinical use.