叶酸偶联白蛋白纳米粒制备工艺研究.pdfVIP

_______________________________________________________________________________ 叶酸偶联白蛋白纳米粒的制备工艺研究* △ 张良珂 侯世祥 毛声俊 宋相容 陈彤 (四川大学 华西药学院，四川 成都610041) 摘要：采用去溶剂化法制备普通白蛋白纳米粒，利用叶酸活性酯在微碱性条件下与白蛋白纳米粒表面的氨基反应，制得叶酸偶 联白蛋白纳米粒。采用葡聚糖凝胶柱色谱法及紫外分光光度法验证偶联是否成功，并测定叶酸偶联的程度。通过葡聚糖凝胶柱 色谱法可以清楚地看到叶酸偶联白蛋白纳米粒与未反应的叶酸活性酯完全分离，叶酸偶联白蛋白纳米粒与叶酸白蛋白机械混合 物的胰蛋白酶水解液在 358nm 处的紫外吸收图谱基本一致，说明叶酸已经成功地偶联于白蛋白纳米粒的表面。纳米粒形态圆整， 平均粒径为 66nm 。叶酸偶联白蛋白纳米粒制备成功，作为叶酸受体表达丰富的多种肿瘤细胞的主动靶向给药的潜在途径，值 得进一步的关注和研究。 关键词：叶酸；白蛋白；纳米粒；偶联 Study on the Preparation of Folate-conjugated Albumin Nanoparticles Zhang Liangke Hou Shixiang Mao Shengjun Song Xiangrong Chen Tong (West China School of Pharmacy, Sichuan University, Chengdu 610041) Abstact Bovine serum albumin nanoparticles （BSANP ）were prepared by desolvation method. The activated folic acid (N-hydroxysuccinimide ester of folic acid) were conjuated to the surface of BSANP via the amino groups. Then the folate-conjugated BSANPs (folate-BSANP) were purified with Sephadex G-50 column and completely separated from unreacted folic acid. After chymotryptic hydrolysis, the extent of folate conjugation on the BSANP was determined by quantitative ultraviolet(UV) spectrophotometric analysis. The spectrum of trypsin digest of folate-conjugate BSANP is basically identical with that of folate. Folate is expressed successfully on the surface of BSANP. The mean diameter of the folate-BSANP was 66 nm with round shape. Folate-conjugated BSANP was achieved, which represent a potential new drug carrier for tumor cell-selective targeting. Key words Folate ; Bovine serum albumin; Nanoparticles; Conjugate 受体和其配体的结合具有特异性、选择性、饱和性、亲合力强和生物效应明显等特点。利用配体为药物或放 射性核素的载体，通过受体介导作用，增加药物在病灶局部的浓度、提高疗效，降低毒副作用，达到靶向治疗 目的，是目前研究最活跃的前沿领域之一。随着对细胞膜表面叶酸受体认识的逐步深