掺入胆固醇和阴离子磷脂对阿霉素免疫脂质体性能的影响

INFLUENCE OF INCORPORATION OF CHOLESTEROL AND ANIONIC PHOSPHOLIPIDS ON THE PROPERTIES OF ADRIAMYCIN-IMMUNOLIPOSOMES

本文研究了胆固醇和阴离子磷脂的掺入对阿霉素—磷脂酰乙醇胺免疫脂质体包裹效力及其在PBS缓俄冲液和在50%血清中的稳定性的影响,并对这种影响可能的机理进行了讨论.阴离子磷脂PG和DPG的掺入使ADM免疫脂质体包裹ADM的效力大大增加,使ADM与PE的克分子比从(0.08—0.8)%增加到75%,其中DPG比PG更有效.掺入胆固醇可以明显提高ADM脂质体在缓冲液和在血清中的稳定性,但使脂质体包裹ADM的效力下降.通过脂质的选择和制备条件的摸索,我们成功地用超声法制备了包裹抗癌药(ADM),表面带有抗人胃癌细胞M85单克隆抗体3HII的小单层脂质体(SUV),其起脂质份是PE:PG:Chol:ADM(4:2:2:1),脂质体内的ADM与PE的克分子比为17—25%.经电镜观察,脂质体直径在60—80nm范围内,大以比较均一.这种脂质体在PBS缓冲液中于室温下保存12天,仍然能够保持其包裹药的70%;在50%的血清中,37℃1小时,能够保持其包裹药的80%.

The influence of the incorporation of cholesterol and anionic phospholipids on the potency of PE immunoliposomes to entrap ADM and their stability in PBS buffer and in 50% plasma has been investigated. The mechanisms which may be involved in these influences are discussed. Incorporation of PG and DPG enhanced dramatically the potency of PE immunoliposomes to entrap ADM, with molar ratio of ADM to PE increased from (0.08-0.8)% to 75%.And DPG was found to be more effective than PG. Addition of cholesterol to PE/PG or DPG immunoliposomes could increase the stability of liposomes in buffer and in plasma. Concomitantly, the ADM entrapping potency of PE was decreased.We succeeded in preparing the ADM entrapped small unilamellar vesicles (suv) bearing monoclonal antibody 3Hll against human gastric cancer M85 cells on the surface. The composition of the liposomes used is DOPE:PG:CHOL: ADM(4:2:2:1) . The molar ratio of ADM to PE in vesices is 17-25%. The liposomes were examined under electronmicroscope by negative staining technique. The liposome diameter is 60-80nm and is quite homogeneous. 70% and 80% of the entrapped ADM were retained in liposomes after 12 days in PBS buffer at room temperature and in the presence of 50% serum at 37癈 for 1 hour, respectively.