Preparation of Ursodeoxycholic Acid Targeted Liposomes and Solubilizing Efflux Cholesterol Crystals

OBJECTIVE  To prepare ursodeoxycholic acid targeted liposomes and explore the feasibility of its solubilizing intracellular and extracellular cholesterol crystals in the treatment of atherosclerosis.

METHODS  Ursodeoxycholic acid liposomes were prepared by ethanol injection method, and targeted liposomes were modified by Annexin V. The morphology, particle size, drug loading, encapsulation rate and release in vitro were studied. The macrophage model containing cholesterol crystals was constructed to investigate its ability to clear intracellular and extracellular cholesterol crystals and produce and release pro-inflammatory factor IL-1β, and the in vivo pharmacodynamics was studied in atherosclerotic mice.

RESULTS  The prepared ursodeoxycholic acid targeted liposomes were spherical or quasi-spherical(mean particle size 94.3 nm, potential −23.54 mV) with high encapsulation rate(94.8±2.7)%, drug loading(5.4±0.8)% and slow drug release ability. It could significantly solubilize cholesterol crystals, effectively reduce the content of intracellular cholesterol crystals by promoting the effection of intracellular cholesterol, and inhibit the release of inflammatory factors induced by cholesterol crystals in macrophages. After the injection of the tail vein in the model mice, the atherosclerotic plaque at the aortic arch and other sites was effectively reduced.

CONCLUSION Taking cholesterol crystals in atherosclerotic plaques as therapeutic targets, the annexin-V-modified ursodeoxycholic acid targeting liposomes are successfully constructed, to simultaneously clear intracellular and extracellular cholesterol crystals in plaques and alleviate the release of pro-inflammatory factors by macrophages, thus treating atherosclerosis.