5-FU变形脂质体工艺的改进及其体外透瘢痕的实验研究

Optimization of 5-FU deformable liposomes and experiements with their scar penetration in vitro

目的通过改进5-氟尿嘧啶(5-FU)变形脂质体的工艺,提高其包封率,探索体外渗透治疗瘢痕的有效方法。方法采用薄膜水化法制备5-FU变形脂质体,利用正交实验探索最佳工艺,检测脂质体的形态、粒径分布、包封率等特性。采用改良Franz扩散池,将改进的5-FU变形脂质体进行体外透瘢痕实验后,行瘢痕切片制备和荧光观察。结果各因素对包封率影响大小的顺序:去氧胆酸钠>5-FU>卵磷脂>超声时间>乳化时间,制备的脂质体为圆球形,粒径均匀,平均粒径为(90±5)nm,包封率达82.14%。体外透瘢痕实验5-FU累积透过量低于5%,滞留于瘢痕内的5-FU累积量高达45%,主要集中在瘢痕的表皮层和真皮浅层。结论改进后的5-FU变形脂质体,其包封率较高、粒径较小且均匀,能渗透到瘢痕的表皮层和真皮浅层。

Objective To improve the encapsulation efficiency of 5 - FU by optimizing the technology of 5 - FU deformable liposomes, and research their scar penetration in vitro. Methods The 5 - FU deformable liposome was prepared by the thin film hydration method, and the optimal method was determined by the orthogonal test. The amorphous, size distribution and the encapsulation efficiency of the 5 - FU deformable liposome were investigated. Their scar penetration in vitro was evaluated with the improved Franz diffusion cell. Results The effect of factors on the eacapsulation efficiency of the 5 - FU deformable liposome were randed as follow： sodium deoxycholate 〉 5 - FU〉soybean lecithin〉the time of ultra- sound〉the time of emulsification. The liposcomes were spherical vesicles with uniform sizes. The mean diameter of the 5 - FU deformable liposome was （90 ± 5 ） nm. The entrapment efficiency of these 5 - FU liposorne was as high as 82.14 %. In vitro, the accumulated mass of 5 - FU which passed through scar was below 5 %. However, that retained in the scar was 45 %. The deformable liposome mainly concerttrated in the epidermis and the top of the corium as observed by microphotographs by CLSM. Conclusion 5 - FU deformable liposomes with higher encapsulation efficiency and smaller, uniform sizes may be obtained by optimizing the formulation. These liposorne can penetrate the epidermis and the top of the corium of scar.