Preparation, in vitro and in vivo evaluation of pinocembrin-loaded TPGS modified liposomes with enhanced bioavailability and antihyperglycemic activity

Purpose To prepare polyethylene glycol succinate-vitamin E modified pinocembrin (PCB)-loaded liposomes (PCBT-liposomes) and evaluate PCBT-liposomal pharmacokinetics and antihyperglycemic activity. Significance The novel PCBT-liposomes demonstrated a promising application prospect as a nano drug carrier for future research. Methods Thin film dispersion was used to prepare PCBT-liposomes. We measured a series of characterization, followed by in vitro cumulative release, in vivo pharmacokinetic study, and antihyperglycemic activity evaluation. Results PCBT-liposomes displayed spherical and bilayered nanoparticles with mean particle size (roughly 92 nm), negative zeta potential (about -26.650 mV), high drug encapsulation efficiency (87.32 +/- 1.34%) and good storage (at 4 or 25 degrees C) stability during 48 h after hydration. The cumulative release rate of PCBT-liposomes was markedly higher than free PCB in four different pH media. In vivo investigation showed that PCBT-liposomes could obviously improve oral bioavailability of PCB by 1.96 times, whereas the C (max), MRT0- (t) , and T (1/2) of PCBT-liposomes were roughly 1.700 +/- 0.139 mu g center dot mL(-1), 12.695 +/- 1.647 h, and 14.244 h, respectively. In terms of biochemical analysis, aspartate amino-transferase (AST), alanine amino-transferase (ALT), interleukin-1 (IL-1), and tumor necrosis factor-alpha (TNF-alpha) concentrations in serum of diabetic mice were respectively decreased 28.28%, 17.23%, 17.77%, and 8.08% after PCBT-liposomal treatment. Conclusion These results show PCBT-liposomal preparation as an excellent nano-carrier which has the potential to improve water solubility, bioavailability, and antihyperglycemic activity of PCB, amid broadening the application of PCB in the clinical settings.