硫酸氨基葡萄糖脂质体的制备及其对骨关节炎的治疗作用

目的: 构建与评价硫酸氨基葡萄糖脂质体（glucosamine sulfate liposome,GAS Lips）,并比较游离硫酸氨基葡萄糖（GAS）和GAS-Lips对前交叉韧带横断术（anterior cruciate ligament transection,ACLT）构建的骨关节炎大鼠的治疗效果。方法: 采用薄膜分散法构建GAS Lips,并对其粒径、形貌、载药量与体内滞留性进行评价。24只SD大鼠随机分为假手术组、ACLT+未给药组、ACLT+GAS组、ACLT+GAS Lips组。通过关节腔注射生理盐水、GAS与GAS Lips进行体内药效实验,并观察其对骨关节炎的治疗作用。结果: 表征实验结果表明,GAS-Lips平均粒径为（255.02±3.64）nm,形状为类球形。制剂学评价结果表明,包封率为（78.62±1.01）%,载药量为（9.90±0.75）%,并具有良好的缓释作用。体内滞留实验表明,与对照组相比,Cy3-Lips组在关节腔滞留时间明显延长（P<0.01）。体内药效实验表明,与游离GAS相比,GAS-Lips可以更有效缓解关节表面损伤,抑制炎症因子的表达（P均<0.01）,且对大鼠的体重无明显影响。结论: 本研究成功构建与评价了一种GAS-Lips,提高了GAS在骨关节炎滞留时间与治疗效果,为其开发成为骨关节炎纳米制剂提供研究基础。

Preparation of sulfate glucosamine liposome and its therapeutic effect on osteoarthritis

Objective: To construct and evaluate glucosamine sulfate liposome （GAS-Lips）, compare the treatment of glucosamine sulfate （GAS） and GAS-Lips on osteoarthritis from anterior cruciate ligament transection （ACLT）. Methods: The GAS Lips were constructed by film dispersion method and evaluated for their particle size, morphology, drug loading content and retention in vivo. Twenty four SD rats were randomly divided into sham operation group, ACLT+ untreated group, ACLT+GAS group, and ACLT+GAS-Lips group. In vivo efficacy experiments were carried out by injecting normal saline, GAS and GAS-Lips into the joint cavity, and their therapeutic effects on osteoarthritis were observed. Results: The result of characterization experiment showed that an average particle size is （255.02±3.64） nm, with a spherical shape. The pharmaceutics evaluation showed that the GAS-Lips had a entrapment efficiency of （78.62±1.01）%, and drug loading content of （9.90±0.75）%, and had a good sustained-release effect. In vivo retention experiments showed that the Cy3-Lips group was significantly longer in the joint cavity when compared with the control group （P<0.01）. In vivo efficacy experiments showed that GAS-Lips were more effective in alleviating joint surface damage than free GAS, inhibited the expression of inflammatory factors （both P<0.01）, and had no significant effect on body mass in rats. Conclusion: This study successfully constructed and evaluated a GAS-Lips, improved the retention time and treatment effect of GAS in osteoarthritis, and provided the research basis for its development into osteoarthritis nano-preparation. ［Key words］glucosamine sulfate; liposome; osteoarthritis; joint cavity injection; nano preparation; inflammatory factors