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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(VECF)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:采用薄膜分散一超声法制备脂质体,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VECF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l司醇-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℃,pH7.5的磷酸二氢钠缓冲液脱膜,超声3 min(超声时间2s,间隔3s,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)mV,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 with paeonol-resistant vascular endothelial growth factor (VECF) antibody for the prevention and treatment of hypertrophic scars and to establish a method for evaluating the quality of the liposomes and to investigate the dermal retention effect. Methods: The liposomes were prepared by membrane-disperse-ultrasonication. The encapsulation efficiency was used as evaluation index. The preparation process of liposomes was optimized by Box-Behnken response surface method. The liposomes were observed by transmission electron microscope , Particle size and Zeta potential were measured by laser particle size analyzer, and the dermis retention effect of the liposome was investigated by Franz diffusion cell method. Results: The best preparation technology of paeonol VECF antibody modified liposomes was as follows: lecithin-bilestanol-paeonol- (p-nitrophenyl ester) - polyethylene glycol 3000-dioleoylphosphatidylethanolamine) - (bevacizumab-polyethylene glycol 3000-dioleoylphosphatidylethanolamine) (14: 5: 4: 0.28: 0.05), a film formation temperature of 41 (73.61 ± 2.36)%, average particle size (235.7 ± 4.67) nm, the average particle size was , Zeta potential- (5.13 ± 0.25) mV. The transdermal rate of paeonol VEGF antibody modified liposomes was slow and the dermal retention effect was significant. Conclusion: The preparation process of paeonol VEGF antibody modified liposomes is reasonable and feasible, and the entrapment efficiency High, good in vitro transdermal performance with sustained release effect; drug dermal retention was significantly higher than paeonol drug substance and paeonol liposomes.