结肠定位壳聚糖包衣氟尿嘧啶脂质体的制备、形态与体外释放

Preparation,morphology and in vitro release of chitosan coated liposomes of fluorouracil for colon targeting

目的 探讨药物结肠定位壳聚糖包衣脂质体的制备、形态及其在体外释药特性。方法 用罗丹明B异硫氰酸 (RBITC)和Bodipy PC分别标记壳聚糖和磷脂 ,用前体脂质体方法制备氟尿嘧啶脂质体 ,利用激光扫描共聚焦显微镜观察壳聚糖包衣脂质体的形态 ;考察壳聚糖包衣脂质体在人工胃液、人工肠液和人工结肠液中的释放。结果脂质体包衣前后粒径分别为 2 0 71和 2 75 0 μm。壳聚糖能较好地包覆脂质体 ;3种脂质材料不同的包封率分别为 99% ,6 1% ,72 %。未包衣的脂质体在人工胃液中 4h已释放完全 ,而包衣脂质体在人工胃液 4h释放 6 3% ,在人工肠液中 8h仅释放 6 8% ,但在人工结肠液中释药明显加快 ,t1 2 为 3 6 3h。结论 结肠定位壳聚糖包衣脂质体制备可行 ,在人工结肠液中 ,体外释放符合Higuchi方程。

Aim To prepare chitosan-coated liposomes of fluorouracil for colon targeting and investigate their morphology and in vitro release. Methods Rhodamine B isothiocyanate and Bodipy-PC were used to label chitosan and the liposomes, respectively. Laser confocal scanning microscopy was used to explore the structure of chitosan-coated liposomes, and the release of chitosan-coated liposomes in simulated gastric solution, simulated enteric fluid and simulated colon fluid were investigated. Results The size of liposomes was measured by laser diffraction before and after polymer coating. The mean diameter of liposomes was in the range of 1.43-3.82 μm, whereas after coating 2.06-5.62 μm. For three types of liposomes, negatively charged, positively charged and neutrally charged, the entrapment rate was 99%, 61%, and 72%, respectively. The cumulative release of chitosan-coated liposomes in simulated gastric fluid was only 6.28% in 4 h, and in simulated enteric fluid only 6.8% in 8 h. But in the simulated colon fluid contained β-glucosidase the release was rapidly increased to a t 1/2 of 3.63 h. Conclusion The preparation technology of chitosan-coated liposomes for colon targeting was feasible. In vitro release in the simulated colon fluid was fitted to Higuchi equation.