反义寡核苷酸pH敏前体脂质体的制备及性质分析

Preparation of pH-Sensitive Preliposomes and the Application in Encapsulation of Antisense Oligodeoxynucleotides.

为了提高反义寡核苷酸的稳定性和生物利用度及避免在溶酶体内降解 ,采用旋转蒸发 薄膜水化、超声 挤压、冻干三步法完成 pH敏前体脂质体的制备 ,研究了体外释药规律 ;以反义寡核苷酸为实验对象 ,测定了包封率 .制得的pH敏前体脂质体复水后形成的 pH敏脂质体形态圆整 ,粒径 12 3～ 389 9nm范围内 ,平均粒径为2 2 7nm ;三批 pH敏脂质体的平均包封率为 6 8 3% ;体外释药方程为Q =1 8382 - 2 5 186× 10 -2 T (r =0 9913) ;结果说明制备的 pH敏前体脂质体水合形成的 pH敏脂质体粒度适宜 ,可用于反义寡核苷酸的包封 .

To increase the stability and bioavailability of antisense oligodeoxynucleotides, and to avoid being destroyed by the lysosomes, pH sensitive prelip osomes were preparaed by using of dehydration rehydration , ultrasonication, extrusion, lyophilization methods. The effects of different variables on the preparation of pH sensitive preliposomes were studied . The optimized preparation conditions of pH sensitive preliposomes were acquired through orthogonal test. The experiment revealed that the pH sensitive liposome was regular in its morphology with a mean diameter of 22 7 nm. The mean entrapment efficiency of antisense oligodeoxynucleotides of three batches was 68 3%. The release properties could be expressed by the following equation: Q =1 8382-2 5186×10 -2 T ( r =0 9913).Based upon the various assays used to measure the entrapment efficiency and diameter of pH sensitive liposomes, it was concluded that the entrapment of antisense oligodeoxynucleotides by pH sensitive preliposomes was effective.