作者简介：文章通讯作者张其清研究员，主要从事生物材料、组织工程、纳米技术、控制释药物制剂、医疗器械和安全性评价等课题及项目的研究、产品开发和研究生指导工作。近10多年组织承担过并正承担国家自然科学基金、“八六三”、“九七三”计划等国家、省部级科研项目共77项， 鉴定及结题成果39项，申请专利18项，已获专利11项，在此领域发表论文150余篇，出版专著4部，获各级科技奖10多项。

实验室介绍：本实验在天津市生物医学材料重点实验室完成。该实验室主要从事生物医学材料、组织工程、纳米技术和控制释放药物体系等课题及项目的研究。近10多年来，承担过并正承担着国家自然科学基金、国家“八五”攻关、 “十五”攻关、“八六三”、“九七三”计划、国家重点科技项目、国家重点新产品计划项目、国家高技术产业化示范工程项目、国家火炬计划、国家科技部中央级科研院所社会公益研究专项基金、国家杰出青年基金、国家教委博士点基金、省、部和中国医学科学院级项目等几十项课题的研究开发工作。

同行评价：胆甾醇琥珀酰基壳聚糖锚定脂质体与传统脂质体相比具有一定的优势，有利于提高脂质体药物的稳定性和长效性，值得进行深入的研究。本文数据翔实、具有说服力，且行文流畅，是一篇具有较高学术价值的论文。

摘要
背景：多糖“锚定”脂质体在抗肿瘤药物、蛋白以及基因的传输领域有着极其重要的理论及应用价值，国外已有较多机构在进行相关的研究。
目的：通过“锚定”的方式制备胆甾醇琥珀酰基壳聚糖锚定脂质体，并以表阿霉素作为模型药物，考察其对包载药物体外释放性质的影响。
设计、时间及地点：体外实验, 于2006-09/2008-05在天津市生物医学材料重点实验室完成。
材料：以壳聚糖为原料，合成胆甾醇琥珀酰基壳聚糖，并采用胶体滴定法测定其胆甾醇基取代度。
方法：采用pH梯度法制备表阿霉素脂质体，然后通过共孵育的方法合成了取代度为2.80%，5.58%和8.00%的载药胆甾醇琥珀酰基壳聚糖锚定脂质体。
主要观察指标：荧光分光光度计检测药物浓度；透射电镜观察脂质体形态；亚微米粒度及电位分析仪检测脂质体的粒径大小、分布和电位；动态透析法考察包载药物表阿霉素在胆甾醇琥珀酰基壳聚糖锚定脂质体中的体外释放特征。
结果：胆甾醇琥珀酰基壳聚糖锚定脂质体为规则球状形态，呈现典型的核壳结构，粒径为245.4~279.7 nm，zeta电位为 +21.09 ~ +25.48 mV；和载药脂质体及壳聚糖包衣脂质体相比，CHCS锚定脂质体能明显延缓表阿霉素的体外释放，在胆甾醇基取代度2.80%~ 5.85%范围内，表阿霉素的释放速度随着取代度的增加呈降低的趋势。
结论：胆甾醇琥珀酰基壳聚糖锚定脂质体有着比普通脂质体及壳聚糖包衣脂质体更高的稳定性，能显著延缓包载药物的释放速度。
关键词：胆甾醇琥珀酰基壳聚糖；锚定脂质体；表阿霉素；药物载体；生物材料

涂韶丽，王银松，刘玲蓉，杨心督，杨文智，陈红丽，张其清.胆甾醇琥珀酰基壳聚糖锚定脂质体用作表阿霉素载体的体外实验[J].中国组织工程研究与临床康复，2008，12(19):3663-3666
[www.zglckf.com/zglckf/ejournal/upfiles/08-19/19k-3663(ps).pdf]

In vitro study of cholesterol succinyl chitosan anchored liposomes as a carrier for epirubicin

Abstract
BACKGROUND:Polysaccharides anchored liposomes play an extremely important role in the fields of antitumor drug, protein and gene transmission. Related research is also present abroad.
OBJECTIVE: To prepare cholesterol succinyl chitosan (CHCS) anchored liposomes, and to investigate the effect of CHCS anchored liposomes on the release property in vitro of loading drugs taking epirubicin as a model drug.
DESIGN, TIME AND SETTING: A study in vitro was performed in the Key Laboratory of Biomedical Materials of Tianjin (China) from September 2006 to May 2008.
MATERIALS: CHCS conjugates were synthesized and their substitution degree of cholesterol moiety was determined by colloidal titration method.
METHODS: Epirubicin-loaded liposomes were prepared using pH gradient method, and then CHCS anchored liposomes with epirubicin loading were prepared by incubating method, harvesting the substitution degree of 2.80%, 5.58% and 8.00%.
MAIN OUTCOME MEASURES: Drug concentration was detected by spectrofluorimeter; Liposomes were characterized by transmission electron microscopy; The particle size of liposomes was assayed by submicron particle size analyzer and zeta potential technologies; The release behavior of epirubicin from CHCS anchored liposomes in vitro was investigated by dynamic dialysis method.
RESULTS: CHCS anchored liposomes were almost spherical in shape and had a classic shell-core structure. The sizes of CHCS anchored liposomes ranged from 245.4 nm to 279.7 nm and the zeta potential values were in the range of +21.09 mV to +25.48 mV. Compared to epirubicin-loaded liposomes and chitosan-coated liposomes, CHCS anchored liposomes significantly sustained the release of epirubicin in vitro, and the release rate decreased with substitution degree of cholesterol moiety increasing at a range of 2.80%-5.85%.
CONCLUSION: CHCS anchored liposomes are more stable than common liposomes and chitosan-coated liposomes, and they can significantly sustain the release of loading drug.

Tu SL, Wang YS, Liu LR, Yang XD, Yang WZ, Chen HL, Zhang QQ. In vitro study of cholesterol succinyl chitosan anchored liposomes as a carrier for epirubicin.Zhongguo Zuzhi Gongcheng Yanjiu yu Linchuang Kangfu 2008;12(19):3663-3666
[www.zglckf.com/zglckf/ejournal/upfiles/08-19/19k-3663(ps).pdf]