Reno protective potential of taxifolin liposomes modified by chitosan in diabetic mice

The objective of this study was to develop chitosan-modified taxifolin liposomes (CTL) to enhance the treatment of diabetic kidney injury in mice and to address the limitations of taxifolin (TAX) solubility and bioavailability. Taxifolin liposomes (TL) were fabricated via film dispersion and subsequently modified with chitosan to obtain CTL. Characterisation analyses confirmed the successful construction of the liposomes. In vivo pharmacokinetic studies compared the bioavailability of CTL with those of free TAX and unmodified TL. A streptozotocin-induced diabetic nephropathy mouse model was used to investigate the reno protective effects of CTL. TL had an encapsulation efficiency (EE) of 89.61 % ± 2.51 % and drug-loading capacity (DL) of 16.07 % ± 0.70 %, while CTL had an EE of 84.57 % ± 2.95 % and DL of 14.48 % ± 0.41 %. The zeta potential of TL was -33.16 ± 5.22 mV, whereas that of CTL was +31.41 ± 3.05 mV. The particle size of TL and CTL was 136.69 ± 0.37 nm and 286.68 ± 4.99 nm, respectively. CTL showed superior bioavailability; reduced serum urea nitrogen, creatinine, total cholesterol, and triglyceride levels in diabetic mice; and improved kidney tissue damage. Importantly, CTL inhibited the activation of the NF-κB/NLRP3/caspase-1/IL-1β signalling pathway and ameliorated kidney injury. In conclusion, CTL enhanced the sustained release of TAX from simulated gastrointestinal fluids, improved pharmacokinetics, reduced pathological markers, and protected the kidneys at the molecular level.