负载生长激素脂质体温敏凝胶的制备及体外释放效果

Preparation of load growth hormone liposome thermosensitive gel and in vitro release

目的以磷脂酰乙醇胺(PE)、胆固醇,油酸制备生长激素脂质体,并将制备的脂质体负载到PLGA-PEGPLGA温敏凝胶中,实现药物的智能控制释放。方法测定生长激素含量及确定检测波长,精密吸取生长激素溶液,配制不同浓度的生长激素标准溶液,测定吸光度值,建立标准曲线,测定回收率。制备负载生长激素的脂质体并考察脂质体的理化性质。制备凝胶和空白聚合物凝胶,并将一定量的负载生长激素脂质体加入空白聚合物凝胶PLGA-PEG-PLGA溶液中即得到含有药物的凝胶。采用无膜扩散法测定药物从凝胶中的释放效果。结果多次重复实验发现,制备的脂质体包封率和载药量均较高且变化并不大,方法具有较好的重现性。脂质体主要分布在567nm左右,具有较好的分散度。聚合物溶液相转变温度的测定结果显示,随着不同聚合物浓度的增加,相转变温度逐渐降低,最终选择15%浓度制备凝胶。其溶液-凝胶相转变温度为34.5℃,且通针性较好,溶液状态澄清透明。体外释放度的测定结果表明,药物具有透过PLGA-PEG-PLGA三嵌段聚合物网状结构释放的作用,凝胶和脂质体对药物有双重保护作用,具有缓释效果。结论以PE、胆固醇、油酸及PLGA-PEG-PLGA成功制备了生长激素脂质体温敏凝胶,在体外具有很好的缓释效果。

Objective To prepare the growth hormone liposomes by phosphatidyl ethanolamine(PE),and we load the prepared liposomes into a PLGA-PEG-PLGA thermosensitive gel to achieve the release of drugs.Methods The content of growth hormone and wavelength were determined,and different concentration of growth hormone liquid was prepared.Then we determined the absorbance values,established the standard curve and determined the recovery.Liposomes loaded with growth hormone were prepared and the physical and chemical properties were detected.The growth hormone liposomes were loaded into thermosensitive PLGA-PEG-PLGA gels and the drug release was detected with membrane diffusion method.Results The coating rate and drug loading of liposomes were high with good reproducibility.Liposomes were mainly distributed in567nm with good dispersion.With the increase of different polymer concentration and decrease of the transition temperature,15%concentration was chosen to prepare the gel.The solution-gel transition temperature was34.5℃with good ability to pass through needles.The results of in vitro release showed that the drugs went through the PLGA-PEG-PLGA network structure and the liposome and gel had double-protective effects on drugs.Conclusion The growth hormone lipsome temperature-sensitive gel is prepared successfully by PE,cholesterol,oleic acid and PLGA-PEG-PLGA,and it exhibits better sustained-release efficacy in vitro.