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

Abstract

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 °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, MRT_0–t, and T_1/2 of PCBT-liposomes were roughly 1.700 ± 0.139 µg·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-α (TNF-α) 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.

Graphical Abstract

Keywords:

• Pinocembrin
• TPGS
• liposome
• solubility
• oral bioavailability
• antihyperglycemic

Acknowledgements

The authors are thankful to the Ethics Committee of Jiangsu University for Care and Use of Experimental Animals, and Jiangsu Provincial Research Center for Medicinal Function Development of New Food Resources. In addition, the authors also would like to thank Michael Adu-Frimpong et al. for editing and reviewing this work.

Disclosure statement

The authors declare that they have no conflict of interest.

Additional information

Funding

This work was funded by National Key R&D Program of China (2018YFE0208600), National Natural Science Foundation of China (81720108030 and 8217131836), Postdoctoral Research Fund of Jiangsu Province in 2021 category A (2021K010A), Natural Science Foundation of the Higher Education Institutions of Jiangsu Province (18KJB360001), Natural Science Foundation of Jiangsu Province (BK20180866), and Key Planning Social Development Projects of Zhenjiang in Jiangsu Province (SH2021024).