CN1923287A - 载药磁性手性壳聚糖纳米粒子 - Google Patents
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Abstract
一种能够靶向定位并能控制药物释放速率的载药磁性手性壳聚糖纳米粒子。它是以手性壳聚糖作为包覆膜，内含磁性Fe3O4和药物，所形成的复合物的粒径具有10－1000nm的纳米尺寸。利用手性壳聚糖的分子识别作用以及磁性粒子在外加磁场的导向作用实现药物的靶向定位，改变粒子的大小、结构可控制药物的释放速率。
Description
所属技术领域
本发明涉及一种包含有药物的微粒，尤其是在临床上能靶向定位、控制药物释放速率的具有磁性的载药壳聚糖纳米粒子。
背景技术
常用的低分子药物虽然疗效高，使用方便，但由于药物分子对靶分子缺少定位作用，而普遍存在很大的毒副作用，给病人带来极大的生理上和心理上的痛苦。此外小分子药物还有代谢快、半衰期短等缺点。为了克服这些缺点，将无机、有机材料作为药物的载体，制成一定的剂型，构成“靶向药物控释体系”，把药物靶向定位于靶组织，并进行可控释放，从而具有长效、高效、低毒、缓释、选择性好、副作用小等优点[1-4]。
1.李和平.卟啉化合物的合成及其在医学上的应用[M]，湖南科技出版社，2003年3月
2.Nori A，Kopecek J.Intracellular targeting of polymer-bound drugs for cancer chemotherapy[J]，AdvancedDrug Delivery Reviews，2005，(57)：609-636
3.Torchilin V P.Drug targeting[J]，European Journal of Pharmaceutical Sciences.，2000，11 Suppl.(2)：S81-S91
4.Marcucci F，Lefoulon F.Active targeting with particulate drug carriers in tumor therapy：fundamentals andrecent progress[J].Drug Discovery Today.2004，9(5)：219-228
发明内容
为了克服现有药物靶向定位能力差、药物释放速率无法控制的不足，本发明以天然手性小分子对壳聚糖的结构进行化学修饰，制备手性药物载体，以磁性Fe3O4纳米粒子作为内核，结合靶向给药和智能释药优点用纳米技术制备的智能纳米药物粒子。该纳米药物粒子能通过感应病变部位环境信息的变化，从而调节药物的释放速率，使药物在必要的时间和特定部位释放出所需的有效剂量，实现药物的定点、定时、定量控制释放，还能根据用药环境的变化，自我调整释药速率。因此，可解决重大疾病的诊断和治疗。
1.要解决的技术问题
本发明解决其技术问题所采用的技术方案是：以天然手性分子(L-氨基酸)对壳聚糖进行分子结构修饰，合成一系列手性壳聚糖；在此基础上，以Fe3O4纳米粒子为内核，以5-氟尿嘧啶等抗癌药物为模型药物，制备载药磁性手性壳聚糖纳米粒子。利用手性分子对生物大分子的识别作用以进行化学导向；利用Fe3O4纳米粒子的磁性，在外加磁场作用下，进一步进行物理导向；对载药磁性手性壳聚糖纳米粒子的大小、载药率、交联度等进行控制，从而实现对药物释放速率的控制。通过载体对病变部位环境信息变化的感应，从而调节药物的释放速率。
2.技术方案
2.1 Fe3O4纳米粒子的制备
将2.3g市售磁粉(Fe3O4)在氮气保护下用25mL浓盐酸溶解，形成黄褐色透明溶液，加入适量表面活性剂在剧烈搅拌下缓慢滴加氨水，当pH＝6～9时产生大量的黑色粒子，在60～80℃下陈化0.5～1h，室温静置24h，弃去上层清夜，用蒸馏水洗涤3次。然后在超声作用下进行磁分离提纯，再将Fe3O4粒子分散于100mL蒸馏水中，制得泥糊状Fe3O4纳米粒子。
2.2手性壳聚糖的合成
以天然手性分子(L-氨基酸)对壳聚糖进行结构修饰，连接基为酰胺键，合成路线如下：
壳聚糖 手性壳聚糖
R-COOH为大然手性化合物，如L-氨基酸等。
L-氨基酸对壳聚糖分子的接枝率由R-COOH与壳聚糖的投料比来控制。
基本实施步骤：称取1.0g氨基酸以稀盐酸溶解，将此溶液缓慢滴加到壳聚糖的醋酸溶液中，40-80℃下反应4-6h，冷却到室温；调节pH值至7～9，静置，抽滤，分别用80％的甲醇及无水乙醇洗涤2-3次，真空干燥得产品。
2.3载药磁性手性壳聚糖纳米粒子的制备
在250mL三颈烧瓶中，加入0.7克手性壳聚糖溶液及适量离子分散剂，加入0.2克冰醋酸，10mL水，搅拌使溶解。再加入100mL苯甲酸乙酯、10mg上述制备得到的Fe3O4纳米粒子及适量药物，剧烈搅拌并采用超声波超声10-15min，再由滴液漏斗缓慢滴加1-5mL 50％的戊二醛溶液，交联聚合使反应完全。冷却，离心，弃去上层清夜，下层泥糊状纳米粒子经洗涤，真空冷冻干燥。
3有益效果
本发明的有益效果是，可以将药物靶向输送到病变部位，并能控制药物的释放速率。从而降低药物的毒副作用，提高疗效。
附图说明
下面结合附图和实施例对本发明进一步说明。
图1是本发明的载药磁性手性壳聚糖纳米粒子外形图。
图2是本发明的载药磁性手性壳聚糖纳米粒子纵剖面构造图。
图中，1.手性壳聚糖包覆膜，2.Fe3O4纳米粒子，3.药物。
具体实施方式
在图1中，手性壳聚糖包覆膜(1)包裹Fe3O4纳米粒子(2)和药物(3)，有少量的(2)和(3)可能沾附于(1)的外表面或贯穿于其中。
在图2所示实施例中，大部分的Fe3O4纳米粒子(2)和药物(3)在手性壳聚糖包覆膜(1)的腔内，但有少量的(2)和(3)可能沾附于(1)的外表面或贯穿于其中。
Claims (4)
1.一种载药磁性手性壳聚糖纳米粒子，手性壳聚糖作为外壳包含磁性Fe3O4和药物形成复合的纳米粒子。其特征是：粒子的粒径大小具有10nm-1000nm的纳米尺寸，外型为球形或接近球形，壳聚糖包覆膜具有手性，内含磁性粒子和药物，所含药物重量为粒子总重量的5-95％。
2.根据权利要求1所述的载药磁性手性壳聚糖纳米粒子，其特征是：壳聚糖作为外壳已形成完整的包覆膜(允许少量孔隙存在)，绝大部分的磁性Fe3O4和药物都被包裹于其内，但允许极少量的磁性Fe3O4和药物沾附于壳聚糖膜的外表面。
3.根据权利要求1所述的载药磁性手性壳聚糖纳米粒子，其特征是壳聚糖膜具有手性识别作用，对环境(如pH值、温度等)敏感，能降解且降解速率可控制，药物通过扩散作用和/或膜的降解而渗出。
4.根据权利要求1所述的载药磁性手性壳聚糖纳米粒子，其特征是在外加磁场作用下，具有磁响应性。
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102134334A (zh) * | 2010-12-29 | 2011-07-27 | 厦门大学 | 磁性壳聚糖微球的制备方法 |
| CN102319217A (zh) * | 2011-07-26 | 2012-01-18 | 浙江大学医学院附属妇产科医院 | 一种壳聚糖包衣磁性纳米粒及制备方法 |
| CN102481118A (zh) * | 2009-09-14 | 2012-05-30 | 皇家飞利浦电子股份有限公司 | 用于移动和激活活性剂的设备和方法 |
-
2005
- 2005-11-08 CN CN 200510032346 patent/CN1923287A/zh active Pending
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102481118A (zh) * | 2009-09-14 | 2012-05-30 | 皇家飞利浦电子股份有限公司 | 用于移动和激活活性剂的设备和方法 |
| CN102481118B (zh) * | 2009-09-14 | 2015-08-19 | 皇家飞利浦电子股份有限公司 | 用于移动和激活活性剂的设备 |
| CN102134334A (zh) * | 2010-12-29 | 2011-07-27 | 厦门大学 | 磁性壳聚糖微球的制备方法 |
| CN102134334B (zh) * | 2010-12-29 | 2013-03-13 | 厦门大学 | 磁性壳聚糖微球的制备方法 |
| CN102319217A (zh) * | 2011-07-26 | 2012-01-18 | 浙江大学医学院附属妇产科医院 | 一种壳聚糖包衣磁性纳米粒及制备方法 |
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