羟基酪醇柔性纳米脂质体的制备及其贮藏稳定性研究

Preparation and Storage Stability of Hydroxytyrosol Flexible Nanoliposomes

以羟基酪醇(HT)为原料,氢化卵磷脂和胆固醇为乳化剂,采用薄膜分散法制备HT柔性纳米脂质体并研究其贮藏稳定性。以包封率为响应值,通过单因素、Plackett-Burman和Box-Behnken响应面试验得到制备的最优工艺,同时利用红外光谱、热重、差示扫描量热、透射电镜对产物进行结构表征,并考察该HT的贮藏稳定性。研究结果表明:较佳制备工艺条件为HT 1.5 mg、氢化卵磷脂与胆固醇质量比3.3∶1、叶酸-聚醚(FA-F127)用量1 mg、胆酸钠用量20.6 mg、超声波功率10%(总功率为650 W)、超声波作用时间11 min,在此条件下制备的HT柔性纳米脂质体包封率、粒径、多分散系数(PDI)、Zeta电位分别为46.78%、104.7 nm、0.231、-42.5 mV。结构表征结果表明:HT柔性纳米脂质体是一种有前途的、更高效、更安全的递送系统。贮藏稳定性研究结果显示:HT纳米脂质体分别在4、25、60℃下贮藏28 d,4℃下的包封率为37.56%,粒径为152.7 nm,PDI和Zeta电位变化不大,而25和60℃下的HT纳米脂质体的上述指标变化较大,因此,4℃更利于其稳定贮藏。

Hydroxytyrosol(HT)flexible nano-liposomes were prepared by thin film dispersion method using hydroxytyrosol as raw material,hydrogenated lecithin and cholesterol as emulsifiers and their storage stabilities were studied.The optimum preparation process was obtained by single factor,Plackett-Burman and Box-Behnken response surface tests with the encapsulation rate as the response value.The structure was characterized by infrared spectroscopy,thermogravimetry,differential scanning and transmission electron microscopy,and the storage stabilities of the hydroxytyrosol were investigated.The results showed that the optimum conditions were the mass of hydroxytyrosol of 1.5 mg,the mass ratio of hydrogenated lecithin to cholesterol of 3.3∶1,the dosage of FA-F127 of 1 mg,the dosage of sodium cholate of 20.6 mg,the ultrasonic power of 10%,and the ultrasonic time of 11 min.The encapsulation rate,particle size,polydispersity index(PDI)and Zeta potential of hydroxytyrosol flexible nano-liposomes prepared under these conditions were 46.78%,104.7 nm,0.231 and-42.5 mV,respectively.The results of structural characterization showed that hydroxytyrosol flexible nanoliposomes would be a promising delivery system with higher efficiency and safety.The results of the storage stability study indicated that the hydroxytyrosol nanoliposomes were stored at 4,25 and 60℃for 28 days,respectively.The encapsulation rate at 4℃was 37.56%,the particle size was 152.7 nm,and the PDI and Zeta potential had little change,while the above indexes of hydroxytyrosol nanoliposomes at 25 and 60℃had great changes.Therefore,the optimal process was reliable,and it could be seen that 4℃was more conducive to its stable storage.