Preparation and pharmacokinetic study of diosmetin long-circulating liposomes modified with lactoferrin
2022
Sun, Wen-Xia | Zhang, Chuan-tao | Yu, Xi-Na | Guo, Jia-bin | Ma, Hao | Liu, Ke | Luo, Pei | Ren, Jing
Diosmetin (Dios) is a bioflavonoid mainly isolated from citrus fruits with some health-promoting properties. Recently, diosmetin has been investigated as a promising agent for treating neurodegenerative diseases. However, the poor water solubility of diosmetin restricts its application in various fields. Herein, this study developed novel lactoferrin modified long-circulating liposomes (Lf-Lcl) using a thin-film dispersion-ultrasound method for brain-targeted delivery of diosmetin with potential implications in Alzheimer's disease treatment. A three-factor, three-level Box-Behnken design (BBD) was adopted for the formula optimization with the lipid-to-drug ratio, the amount of cholesterol and the concentration of phospholipids as the independent variables. Transmission electron microscopy (TEM) images of the diosmetin-loaded lactoferrin modified long-circulating liposomes (Lf-Dios-Lcl) showed homogeneous spherical particles with particle size of 173 ± 1.53 nm and zeta potential of − 35.40 ± 0.18 mV. The entrapment efficiency (EE) and dosage loading (DL) of Lf-Dios-Lcl were 80.30% ± 1.17% and 9.27% ± 0.12%, respectively. Moreover, in vitro experiments with Lf-Dios-Lcl exhibited sustained release for more than 24 h. In vivo studies demonstrated extended half-life and higher brain concentration of Lf-Dios-Lcl, indicating its excellent effect on brain targeting. The results provided insight for study nutritional and medicinal value of Lf-Dios-Lcl.
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