丹皮酚VEGF抗体修饰脂质体的制备及其真皮滞留效应考察  

Preparation of Liposomes of Paeonol Modified with VEGF Antibody and Investigation of Its Dermal Retention Effect

作　　者：张慧迪 时军 陈桂添 吴艳婷 郭思旖 

机构地区：[1]广东药科大学中药学院广东省局部精准递药制剂工程技术研究中心

出　　处：《中国实验方剂学杂志》2018年第3期19-24,共6页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：广东省科技计划项目(2014A020212417);广东省高等学校优秀青年教师培养计划项目(YQ2015099);广东省普通高校特色创新项目(2015KTSCX071)

摘　　要：目的：制备具有防治增生性瘢痕作用的丹皮酚血管内皮生长因子（VEGF）抗体修饰脂质体,建立其质量评价方法并考察其真皮滞留效应。方法：采用薄膜分散-超声法制备脂质体,以包封率为评价指标,采用Box-Behnken响应面法优选丹皮酚VEGF抗体修饰脂质体的制备工艺,通过透射电镜观察脂质体形态,激光粒度仪测定粒径及Zeta电位,Franz扩散池法考察该脂质体的真皮滞留效应。结果：丹皮酚VEGF抗体修饰脂质体的最佳制备工艺为磷脂质量浓度7.36 g·L^-1,按卵磷脂-胆固醇-丹皮酚-（对硝基苯酯基-聚乙二醇3000-二油酰磷脂酰乙醇胺）-（贝伐单抗-聚乙二醇3000-二油酰磷脂酰乙醇胺）（14∶5∶4∶0.28∶0.05）,成膜温度41℃,pH 7.5的磷酸二氢钠缓冲液脱膜,超声3 min（超声时间2 s,间隔3 s,功率300 W）;包封率（73.61±2.36）%,平均粒径（235.7±4.67）nm,Zeta电位-（5.13±0.25）m V,丹皮酚VEGF抗体修饰脂质体透皮速率缓慢,真皮滞留效应显著。结论：丹皮酚VEGF抗体修饰脂质体的制备工艺合理可行、包封率较高、体外透皮性能良好且具有缓释效果;药物真皮滞留量显著高于丹皮酚原料药和丹皮酚脂质体。Objective： To prepare liposomes of paeonol modified with vascular endothelial growth factor（VEGF） antibody for preventing and treating hypertrophic scars,and establish its quality evaluation method,as well as study on its dermal retention effect. Method： The liposomes of paeonol modified with VEGF antibody were prepared by thin-film dispersion-ultrasonic method. Taking encapsulation efficiency as index, Box-Behnken response surface methodology was used to optimize the preparation process. The morphology of the liposomes was observed by transmission electron microscopy, particle size and Zeta potential were measured by particle size analyzer,dermal retention effect of the liposomes was determined by Franz diffusion cell method. Result： The optimal preparation conditions were as follows： phospholipid concentration of 7. 36 g·L^-1,lecithin-cholesterolpaeonol-（p NP-PEG3000-DOPE）-（BVE-PEG3000-DOPE）（14 ∶ 5 ∶ 4 ∶ 0. 28 ∶ 0. 05）,film forming temperature of 41 ℃,stripping with pH 7. 5 sodium dihydrogen phosphate buffer solution,ultrasonic time of 3 min（ultrasonic time of 2 s, the interval of 3 s, power of 300 W）; under these conditions, encapsulation efficiency of the liposomes was（73. 61 ± 2. 36） %,particle size was（235. 7 ± 4. 67） nm and Zeta potential was-（5. 13 ±0. 25） m V. Transdermal rate of liposomes of paeonol modified with VEGF antibody was slow and its dermal retention effect was remarkable. Conclusion： This optimized preparation process is reasonable and feasible with high encapsulation efficiency, good in vitro transdermal properties and sustained release effect. Liposomes of paeonol modified with VEGF antibody has obvious retention effect in the dermis layer,which is significantly higher than paeonol liposomes and paeonol raw material.

关 键 词：丹皮酚 血管内皮生长因子 脂质体 真皮滞留效应 贝伐单抗 

分 类 号：R283.6[医药卫生—中药学] R945[医药卫生—中医学]