阿霉素纳米-VEGFR2单抗交联物的制备及药代动力学研究  

Preparation and pharmacokinetics study of immunoconjugate composed of Adriamycin nanoparticles and VEGFR2 monoclonal antibody

作　　者：殷香保[1] 邬林泉[1] 黄明文[1] 罗志强[1] 余新[1] 黄俊[1] 邢宏松[1] 

机构地区：[1]南昌大学第二附属医院普外科,江西南昌330006

出　　处：《中国生化药物杂志》2014年第2期67-70,74,共4页Chinese Journal of Biochemical Pharmaceutics

基　　金：江西省自然科学基金资助项目(2008GQY 0050);国家自然科学基金项资助项目(81060187)

摘　　要：目的研究阿霉素纳米-VEGFR2单抗交联物的制备及药代动力学特点。方法以聚乳酸、壳聚糖为原料,采用复乳法制备阿霉素纳米微粒;以碳化二亚胺(EDC)为交联剂,采用分子交联技术将阿霉素纳米与VEGFR2单抗进行分子交联,制备阿霉素纳米-VEGFR2单抗交联物;ELISA法分析交联物的免疫性反应;再以SD大鼠为实验对象,研究交联物在动物体内的药代动力学特点。结果制备的阿霉素纳米在扫描电镜下为较均一的球形颗粒,粒径为(160±34)nm,载药量为和包封率分别为(30.15±3.5)%和(80.56±4.24)%。制备的阿霉素纳米-VEGFR2单抗交联物保留了VEGFR2与IV型胶原酶以及表达IV型胶原酶的H22细胞的免疫结合活性。交联物对阿霉素有良好的控制释放作用,能够有效降低血药峰浓度,并延长药物在血液中的滞留时间。结论阿霉素纳米-VEGFR2单抗交联物保留了VEGFR2单抗的免疫性,在动物体内具有良好的缓释性。Objective To prepare the immunoconjugate composed of Adriamycin nanoparticles and VEGFR 2 monoclonal antibody(conjugate of ADM-NP and VEGFR 2-MAb) and study its pharmacokinetics property. Methods Adriamycin nanoparticles were prepared by using double emulsion method, with PLA and O-CMC as materials. Conjugate of ADM-NP and VEGFR 2-MAb was prepared by using molecule conjugate technology. Immunoreactivity of the conjugate with type IV collagenase and H 22 cell were analyzed by using ELISA. Pharmacokinetics parameters of the immunoconjugate were obtained by using SD rats as study objects. Results The prepared ADM-NP was sphere particles under SEM, which diameters were (160±34) nm. The drug loading rate and entrapment rate were (30.15±3.5)% and (80.56±4.24)% respectively. Conjugate of ADM-NP and VEGFR 2-MAb was successfully prepared, which had immunoreactivity with type IV collagenase and H 22 cell. The immunoconjugate showed good ADM control-release ability and could prolong the retention time of ADM in vivo. Conclusion Conjugate of ADM-NP and VEGFR 2-MAb keeps the immunoreactivity of VEGFR 2-MAb and shows good ADM control-release ability.

关 键 词：VEGFR2单抗 阿霉素 纳米微粒 

分 类 号：R969.1[医药卫生—药理学]