Advancing diabetes treatment: novel formulation of polydatin long-circulating liposomes and their glucose-regulating impact on hyperlipidemia-induced type 2 diabetic mice

Abstract

Polydatin, a monomer derived from the dried roots and stems of traditional Chinese medicinal herb, Polygonum cuspidatum, boasts extensive pharmacological activities. Existing nanocarriers of polydatin have not been able to prolong the circulation time for enhanced antidiabetic potential of the stilbenoid polyphenol. This study aims to improve the sustained release and antidiabetic potential of polydatin by fabricating long circulating liposomes (PLLs) via a membrane dispersion method. An orthogonal optimized PLL composed of lecithin, DSPE-PEG2000, and cholesterol was produced, wherein evaluation of the physical properties showed that the prepared PLL had a spherical shape with uniform size, small particle size, and even distribution as well as high encapsulation efficiency and drug loading, along with good physical stability at 4 and 25 °C for 30 days. In vivo release experiments in different buffers via the dialysis bag method suggested that the PLL provided a sustained release of polydatin. Also, in vitro cell uptake and in vivo pharmacokinetics studies of the PLL respectively demonstrated improved cellular uptake and prolonged in vivo circulation time and bioavailability. Using a high-fat diet-induced obese type 2 diabetes mellitus (T2DM) mouse model, it was observed that the PLL could lower blood sugar, improve weight loss, reduce antioxidant stress, lower blood lipids, and ameliorate liver, spleen, and pancreatic tissue damage. This study successfully prepared long-circulating liposomes of polydatin, which sustained in vitro release of polydatin, improved bioavailability in vivo, and enhanced the activity of the drug in treating obese diabetic mice.