CN1733313A - 聚氰基丙烯酸正丁酯纳米颗粒的制备方法 - Google Patents

聚氰基丙烯酸正丁酯纳米颗粒的制备方法 Download PDF

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CN1733313A
CN1733313A CNA2004100466493A CN200410046649A CN1733313A CN 1733313 A CN1733313 A CN 1733313A CN A2004100466493 A CNA2004100466493 A CN A2004100466493A CN 200410046649 A CN200410046649 A CN 200410046649A CN 1733313 A CN1733313 A CN 1733313A
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张阳德
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Abstract

一种用十六烷基三乙基溴化铵修饰的聚氰基丙烯酸正丁酯纳米颗粒(CTAB－PBCA－NP)的制备方法，其步骤是：将吐温80溶解于适量水中，在恒温、搅拌下，加入α－氰基丙烯酸正丁酯单体，离心，取上清。过滤，除去上清，制成PBCA－NP胶体储存液。将PBCA－NP胶体储存液稀释，加入到十六烷基三乙基溴化铵(CTAB)水溶液中，室温下搅拌、离心去上清，干燥后即制成CTAB修饰的聚氰基丙烯酸正丁酯纳米颗粒。本发明不仅可有效结合质粒DNA，而且可保护DNA免受破坏，并具有较高的体外基因转运效率。PBCA纳米颗粒基因转运体系，可保护所携带DNA免受核酸酶的降解和超声剪切作用的破坏。

Description

聚氰基丙烯酸正丁脂纳米颗粒的制备方法
                          技术领域
本发明涉及一种对肝癌基因治疗药物纳米颗粒的制备方法，特别是一种十六烷基三乙基溴化铵修饰的聚氰基丙烯酸正丁脂纳米颗粒(CTAB-PBCA-NP)的制备方法。
                          技术背景
近年来，随着基因转移技术的日趋成熟，肝癌的基因治疗已成为生物科学和临床医学的研究热点之一。而调控自杀基因特异性导入肝癌细胞，或在肝癌细胞中实现特异性表达，在最大限度地杀伤肝癌细胞的同时不损害正常肝细胞，是决定其疗效及可行性的关键。目前，基因治疗的研究和临床应用中常用的病毒载体和非病毒载体，都存在无法克服的局限性。纳米粒基因转运体，是近年发展起来的一种非病毒基因转运载体，它将DNA、RNA等基因治疗分子包裹在纳米颗粒中或吸附在其表面，通过靶向分子与细胞表面特异性受体结合，可望实现安全有效的靶向性基因治疗。纳米材料的选择，是成功进行纳米基因转运和治疗的关键。所选择的材料必须是生物可降解型或者易于从体内排泄，而不产生有害的降解产物，且无免疫原性，不引起机体的免疫排斥反应。
                         发明内容
本发明的目的，是要提供一种具有良好生物降解性、生物相容性、无免疫原性的十六烷基三乙基溴化铵修饰的聚氰基丙烯酸正丁脂纳米颗粒(CTAB-PBCA-NP)的制备方法。
本发明聚氰基丙烯酸正丁脂纳米颗粒(PBCA-NP)的制备方法选用乳化聚合法，其步骤是：将吐温80溶解于适量水中，在恒温、搅拌下，加入α-氰基丙烯酸正丁脂单体，离心，取上清。过滤，除去上清，制成PBCA-NP胶体储存液。将PBCA-NP胶体储存液稀释，加入到十六烷基三乙基溴化铵(CTAB)水溶液中，室温下搅拌、离心去上清，干燥后即制成CTAB修饰的聚氰基丙烯酸正丁脂纳米颗粒。
本发明以α-氰基丙烯酸正丁脂单体为原料制成的纳米颗粒基因转运载体，经表面的改性后，不仅可有效结合质粒DNA，而且可保护DNA免受破坏，并具有较高的体外基因转运效率。经实验，本发明有以下效果：1、采用乳化聚合法，优化了工艺条件，成功制备出粒径小、分布均匀的聚氰基丙烯酸正丁脂纳米颗粒。用CTAB修饰该纳米颗粒表面，使其带正电荷从而可逆的结合基因治疗质粒DNA，组装成PBCA纳米颗粒基因转运体系，确定其用于体外基因转染的安全使用浓度为低于100ng/μl。2、PBCA纳米颗粒基因转运体系，可保护所携带DNA免受核酸酶的降解和超声剪切作用的破坏。3、采用绿色荧光报道基因，证实PBCA纳米颗粒基因转运体系外可成功转运外源DNA进入细胞内，转染效率达47％。
                        具体实施方式
下面结合实施例具体介绍本发明。
将吐温80溶解于适量双蒸水中，用0.1N HCl调节溶液的PH值至2.8以下。在恒温磁力搅拌器作用下，向溶液中缓缓加入α-氰基丙烯酸正丁脂单体，室温下继续搅拌5小时。室温、5000rpm离心15min，取上清，用直径0.22μm的滤膜过滤，产物为PBCA-NP。40000rpm离心1小时，除去上清，用双蒸水洗涤两次，干燥后称重，用适量双蒸水重悬沉淀，制成PBCA-NP胶体储存液。
将PBCA-NP胶体储存液稀释为0.625％的水溶液，在磁力搅拌器作用下，取PBCA-NP稀释液16.67ml缓漫加入到33.33ml浓度为0.25％的十六烷基三乙基溴化铵(CTAB)水溶液中，室温，搅拌1小时。40000rpm离心30min，去上清，用双蒸水洗涤，干燥后称重，即制得CTAB修饰的聚氰基丙烯酸正丁脂纳米颗粒。

Claims (2)

1、一种用十六烷基三乙基溴化铵修饰的聚氰基丙烯酸正丁脂纳米颗粒(CTAB-PBCA-NP)的制备方法，其步骤是：将吐温80溶解于适量水中，在恒温、搅拌下，加入α-氰基丙烯酸正丁脂单体，离心，取上清，过滤，除去上清，制成PBCA-NP胶体储存液；将PBCA-NP胶体储存液稀释，加入到十六烷基三乙基溴化铵(CTAB)水溶液中，室温下搅拌、离心去上清，干燥后即制成CTAB修饰的聚氰基丙烯酸正丁脂纳米颗粒。
2、按权利要求1所述的纳米颗粒(CTAB-PBCA-NP)的制备方法，其步骤是：
a、将吐温80溶解于适量双蒸水中，用0.1N HCl调节溶液的PH值至2.8以下，在恒温磁力搅拌器作用下，向溶液中缓缓加入α-氰基丙烯酸正丁脂单体，室温下继续搅拌5小时；室温、5000rpm离心15min，取上清，用直径0.22μm的滤膜过滤，产物为PBCA-NP，40000rpm离心1小时，除去上清，用双蒸水洗涤两次，干燥后称重，用适量双蒸水重悬沉淀，制成PBCA-NP胶体储存液；
b、将PBCA-NP胶体储存液稀释为0.625％的水溶液，在磁力搅拌器作用下，取PBCA-NP稀释液16.67ml缓漫加入到33.33ml浓度为0.25％的十六烷基三乙基溴化铵(CTAB)水溶液中，室温，搅拌1小时；40000rpm离心30min，去上清，用双蒸水洗涤，干燥后称重，即制得CTAB修饰的聚氰基丙烯酸正丁脂纳米颗粒。
CNA2004100466493A 2004-08-11 2004-08-11 聚氰基丙烯酸正丁酯纳米颗粒的制备方法 Pending CN1733313A (zh)

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PCT/CN2004/001089 WO2006015519A1 (fr) 2004-08-11 2004-09-24 Procede de preparation de nanoparticules de polybutylcyanoacrylate modifiees par un bromure de cetyltrietyl-ammonium

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN100460018C (zh) * 2006-07-26 2009-02-11 郑州大学 复溶性聚氰基丙烯酸酯纳米粒,其制备方法及制药用途
CN101259099B (zh) * 2008-01-23 2010-12-01 西北农林科技大学 一种长春花生物碱类抗肿瘤药物的纳米粒制剂及其制备方法

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FR2604903B1 (fr) * 1986-10-08 1989-01-13 Sopar Sa Nv Agents therapeutiques sous forme de particules submicroscopiques contre des parasitoses et compositions pharmaceutiques les contenant
FR2659554B1 (fr) * 1990-03-16 1994-09-30 Oreal Composition pour le traitement cosmetique et/ou pharmaceutique des couches superieures de l'epiderme par application topique sur la peau et procede de preparation correspondant.
IE80468B1 (en) * 1995-04-04 1998-07-29 Elan Corp Plc Controlled release biodegradable nanoparticles containing insulin
CN1417242A (zh) * 2002-11-14 2003-05-14 天津大学 聚乙二醇接枝修饰的聚氰基丙烯酸酯共聚物及其制备方法
CN1243549C (zh) * 2002-11-21 2006-03-01 武汉利元亨药物技术有限公司 熊果酸氰基丙烯酸酯纳米粒冻干粉针剂及其制备方法
CN1181889C (zh) * 2002-12-26 2004-12-29 西安交通大学 口服胰岛素纳米材料的制备工艺

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN100460018C (zh) * 2006-07-26 2009-02-11 郑州大学 复溶性聚氰基丙烯酸酯纳米粒,其制备方法及制药用途
CN101259099B (zh) * 2008-01-23 2010-12-01 西北农林科技大学 一种长春花生物碱类抗肿瘤药物的纳米粒制剂及其制备方法

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