【摘要】：目的:制備葉酸修飾的pH響應(yīng)型阿霉素脂質(zhì)體(FRLD),并對其理化性質(zhì)進行評價。方法:采用硫酸銨梯度法制備FRLD,以包封率為指標運用正交設(shè)計法進行制備工藝的優(yōu)化;用CL-4B瓊脂糖凝膠柱分離-高效液相色譜法測定FRLD的包封率;運用粒徑電位分析儀測定脂質(zhì)體的平均粒徑及Zeta電位,透射電鏡觀察脂質(zhì)體的形態(tài);運用動態(tài)透析法考察FRLD在不同pH環(huán)境中的藥物釋放情況,并考察FRLD在不同pH環(huán)境(pH 7.4和5.5)37℃水浴中的粒徑隨時間的變化情況。結(jié)果:制得的FRLD為圓形或類圓形的大單室脂質(zhì)體,平均粒徑(153.8±2.62)nm,Zeta電位為(-24.62±2.28)mV,平均包封率為89.45%。FRLD在pH 7.4的中性環(huán)境中,藥物釋放緩慢,24 h累積釋放5.5%,而在pH 5.5的酸性環(huán)境中,藥物釋放顯著加快,24 h累計釋放率均達到90.8%,表現(xiàn)出非常強的pH敏感性能。FRLD在pH 7.4的中性環(huán)境中粒徑保持穩(wěn)定,而在pH 5.5的酸性環(huán)境中,粒徑隨孵育時間顯著增加,脂質(zhì)體發(fā)生融合。結(jié)論:采用硫酸銨梯度法制備的FRLD,能獲得較高的包封率,并具有良好的pH響應(yīng)性能。
[Abstract]:Aim: to prepare folic acid modified pH responsive doxorubicin liposome (FRLD), and evaluate its physical and chemical properties. Methods: the preparation of FRLD, by ammonium sulfate gradient method was optimized by orthogonal design, and the encapsulation efficiency of FRLD was determined by CL-4B agarose gel column separation and HPLC. The average particle size and Zeta potential of liposomes were measured by particle size potential analyzer, the morphology of liposomes was observed by transmission electron microscope, and the drug release of FRLD in different pH environments was investigated by dynamic dialysis method. The variation of FRLD particle size with time in different pH environments (pH 7.4 and 5.5) at 37 鈩，

本文編號：2292232