熊去氧胆酸靶向脂质体的制备及其外排胆固醇结晶增溶作用.pdfVIP

熊去氧胆酸靶向脂质体的制备及其外排胆固醇结晶增溶作用

122*

刘珊珊，苏志桂，吴琼珠(1.江苏经贸职业技术学院健康学院，

南京

211168；2.中国药科大学药学院，

南京

211198)

摘要：目的

制备熊去氧胆酸靶向脂质体，探索其增溶动脉粥样硬化斑块胞内、外胆固醇结晶以治疗动脉粥样硬化的可行

性。方法采用乙醇注入法制备熊去氧胆酸脂质体，经膜联蛋白-V表面修饰得到靶向脂质体，并对其形貌、粒径、载药

量、包封率及体外释放进行研究。构建含胆固醇结晶的巨噬细胞模型以考察其清除胞内外的胆固醇结晶和产生、释放促炎

因子IL-1β的能力，并采用动脉粥样硬化模型小鼠进行体内药效学研究。结果所制的熊去氧胆酸靶向脂质体呈粒度均一

的球状或类球状(平均粒径为94.3

nm，电位为−23.54

mV)，且具有较高的包封率(94.8±2.7)%、载药量(5.4±0.8)%及缓慢

的释药能力。该脂质体能够显著增溶胆固醇结晶，且通过促进胞内胆固醇外排，有效降低胞内胆固醇结晶的含量，抑制胆

固醇结晶诱导巨噬细胞炎症因子的释放。给模型小鼠尾静脉注射后，能够有效减少主动脉弓处及其他部位的动脉粥样硬化

斑块。结论以动脉粥样硬化斑块内胆固醇结晶为治疗靶点，成功构建膜联蛋白-V修饰的熊去氧胆酸靶向脂质体，达到

同时清除斑块胞内、外胆固醇结晶，缓解巨噬细胞释放促炎因子，从而治疗动脉粥样硬化的目的。

关键词：熊去氧胆酸；靶向脂质体；胆固醇结晶；动脉粥样硬化

中图分类号：R945文献标志码：B文章编号：1007-7693(2025)07-1140-08

DOI:10.13748/ki.issn1007-7693

引用本文：刘珊珊,

苏志桂,

吴琼珠.

熊去氧胆酸靶向脂质体的制备及其外排胆固醇结晶增溶作用[J].

中国现代应用药学,

2025,

42(7):

1140-1147.

PreparationofUrsodeoxycholicAcidTargetedLiposomesandSolubilizingEffluxCholesterolCrystals

122*

LIU

Shanshan,

SU

Zhigui,

WU

Qiongzhu(1.SchoolofHealthScience,JiangsuVocationalInstituteofCommerce,Nanjing

211168,China;2.CollegeofPharmacy,ChinaPharmaceuticalUniversity,Nanjing211198,China)

ABSTRACT: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

invitro

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

invivo

pharmacodynamics

was

studied

in

atherosclerotic

mice.

RESULTS

The

prepared

ursodeo