CN105902518B - 一种水溶性纳米粒子的制备方法 - Google Patents
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Abstract
本发明公开了一种新型自组装果胶‑熊果酸纳米粒子的制备方法，具体涉及一种以天然果胶为载体，果胶的羧基与熊果酸的羟基以酯健相连，形成果胶‑熊果酸前药，前药与另一种抗癌药物10‑羟基喜树碱自组装形成果胶‑熊果酸/10‑羟基喜树碱纳米粒子。本发明的一种新型自组装果胶‑熊果酸纳米粒子的制备方法载药量高、生物相容性好、可生物降解，大大延长药物在体内的循环时间，弱酸环境下果胶与熊果酸之间的酯键缓慢水解，实现了药物的缓慢释放。利用果胶对结肠癌和肝癌的靶向作用，果胶‑熊果酸/10‑羟基喜树碱纳米药物可以靶向肿瘤病灶，协同杀死肿瘤细胞。
Description
技术领域
本发明属于生物制药和纳米技术领域，涉及药物递送系统，具体涉及一种新型水溶性纳米粒子的制备方法。
背景技术
熊果酸(Ursolic acid，简称UA)、双氢青蒿素(Dihydroartemisinin，简称DHA)难溶于水，直接口服对身体有一定程度的毒副作用，不能针对单一的癌症进行治疗，对癌细胞无识别能力，杀死癌细胞的同时也杀死正常细胞，而且生物利用度较差，这些都限制了UA和DHA在药学领域的广泛应用，因此，解决其水溶性的问题、增加药物稳定性、提高对单一癌细胞缓释杀伤能力是DHA临床应用的关键。
果胶(Pectin)是存在于植物细胞壁中的多糖类大分子物质。广泛存在于苹果、柑橘等水果中，易于提取，与组织器官有很好的相容性，吸收好，无毒副作用，近年来，针对果胶的巨大医学潜力引起了国内外很多学者对果胶的广泛研究，大多是以辅料的形式携载药物到达病灶或通过改性的方法递送药物，其大分子的扩散性差、易聚集等因素限制果胶的生物医药利用。
发明内容
本发明的目的是针对现有技术中的不足，提供一种新型水溶性纳米粒子的制备方法，PET-UA在水介质中可自组装形成纳米粒子，解决UA的水溶相差，生物利用度低等问题，自组装过程同时包裹DHA或HCPT，形成PET-UA(DHA)·NPs和PET-UA(HCPT)·NPs，增大系统的载药量，包裹的药物有很宽的选择，大量的疏水性药物都以实现自组装的同时包裹药物，包裹的药物前后对纳米粒子的粒径影响不大，使用果胶为药物载体，靶向性好，载药量高，避免药物的不完全释放和突释情况对患者带来的毒副作用。
一种新型水溶性纳米粒子的制备方法的技术方案如下：
一种新型水溶性纳米粒子的制备方法，其特征在于，以果胶(PET)为载体，果胶的羧基与熊果酸(UA)的羟基酯化形成高分胶束，再自组装形成纳米粒子PET-UA·NPs，自组装过程中通过包裹双氢青蒿素疏水药物或10-羟基喜树碱，形成PET-UA(DHA)·NPs或PET-UA(HCPT)·NPs，形成具有核壳结构的纳米粒子。
所述果胶酯化度50～75％。
所述的一种新型水溶性纳米粒子的制备方法，其纳米粒子中UA的载药量为0.1％-12％，纳米粒子的质量百分比0.01％-90％，纳米粒子半径10-200nm。
本发明所述的一种新型水溶性纳米粒子的制备方法，包括以下步骤：
(1)取一定量的果胶，缓慢加入冰醋酸、乙酸酐和硫酸，冰浴下反应一段时间，然后升温至50℃，搅拌至溶液澄清，混合物旋蒸，乙醇洗至中性，冷冻干燥，得到乙酰化果胶粉末A；
(2)取一定量的步骤(1)中的粉末A溶于二甲基亚砜(DMSO)，果胶与DMSO的固液比1:20～1:50(g/ml)，加入激活剂1-(3-二甲氨基丙基)-3-乙基碳二亚胺盐酸盐(EDC)，催化剂4-二甲氨基吡啶(DMAP)，按照一定比例加入双氢青蒿素，搅拌反应30～50h，得到反应混合液；
(3)对(2)中反应后的药物进行纯化，向反应后的混合液中加入3V的乙醚/乙醇(1:1，v/v)沉淀，4000rpm离心去上清液，乙醚/乙醇洗涤沉淀5次，离心除去上清液，45℃下真空干燥24h，收集粉末B；
(4)取30mg(3)中的粉末B溶于5ml二甲基亚砜，溶解30min，逐滴滴入高速搅拌的100ml去离子水中，搅拌5min，得到的纳米粒子溶液在PBS溶液中透析12h，每2h换一次透析液，透析膜中的透析液冷冻干燥，得到粉末C，包裹过程是取25mg(3)中冷干物，与5mgDHA或5mg HCPT混合，溶于搅拌的二甲基亚砜中，溶解30min，逐滴滴入高速搅拌的100ml去离子水中，搅拌5min，得到的纳米粒子溶液在PBS溶液中透析12h，每2h换一次透析液，透析膜中的透析液冷冻干燥，分别得到粉末D和E。
优选地，步骤(2)所述的UA与EDC、DMAP的摩尔比为1:0.8:0.2；
优选地，步骤(4)所述的高聚物PET-UA与DHA和HCPT的摩尔比为1:0.5～1:1和1:0.1～1:2；
优选地，步骤(4)所述的UA的载药量为0.1％-12％，纳米粒子的质量百分比0.01％-90％，纳米粒子半径10-200nm；
相对现有技术，本发明具有以下有益效果：
本发明的水溶性纳米粒子的载药量可调，靶向性强，较好的稳定性，生物相容性好，毒性低，具有缓释功能的纳米药物。
附图说明
图1为合成高分子化合物PET-UA的核磁图
图2为纳米粒子的透射电镜形貌图
具体实施方式
下面结合具体实施方式，对本发明作进一步说明。
实施例1、一种新型水溶性纳米粒子的制备方法：
(1)PET的乙酰化
取1g的PET(酯化度50％～80％)，缓慢加入25ml冰醋酸、15ml乙酸酐和0.6ml硫酸，冰浴下反应一段时间，然后升温至50℃，搅拌至溶液澄清，混合物旋蒸，乙醇洗至中性，冷冻干燥，得到乙酰化果胶粉末A。
(2)PET-UA的合成
取(1)中PET 0.1g，缓慢加入含4ml吡啶的25ml圆底烧瓶中，并超声10min，搅拌溶解20min，然后在溶液中加入0.1g激活剂1-(3-二甲氨基丙基)-3-乙基碳二亚胺盐酸盐(EDC)、0.02g催化剂4-二甲氨基吡啶(DMAP)，搅拌30min，加入0.1g的UA，水浴反应48h，得到PET-DHA聚合物混合液。
(3)PET-UA的纯化
对(2)中反应后药液进行纯化，向反应后的混合液中加入3V的乙醚/乙醇(1:1，v/v)沉淀，4000rpm离心去上清液，乙醚/乙醇洗涤沉淀5次，离心除去上清液，45℃下真空干燥24h，收集粉末B；
(4)PET-DHA和HCPT的自组装
取30mg(3)中的粉末B溶于5ml二甲基亚砜，溶解30min，逐滴滴入高速搅拌的100ml去离子水中，搅拌5min，得到的纳米粒子溶液在PBS溶液中透析12h，每2h换一次透析液，透析膜中的透析液冷冻干燥，得到粉末C，包裹过程是取25mg(3)中冷干物，与5mgDHA或5mgHCPT混合，溶于搅拌的二甲基亚砜中，溶解30min，逐滴滴入高速搅拌的100ml去离子水中，搅拌5min，得到的纳米粒子溶液在PBS溶液中透析12h，每2h换一次透析液，透析膜中的透析液冷冻干燥，分别得到粉末D和E粒径大小为20～100nm。
实施例2、一种新型水溶性纳米粒子的制备方法：
在本实例中，通过与实施例1相同的合成方法及步骤，PET 0.1g，UA 0.5g，测得粒径大小为20～80nm。
实施例3、一种新型水溶性纳米粒子的制备方法：
在本实例中，通过与实施例1相同的合成方法及步骤，PET 0.1g，UA 0.05g，测得粒径大小为30～130nm。
Claims (4)
1.一种纳米粒子的制备方法，其特征在于，以果胶(PET)为载体，果胶的羧基与熊果酸(UA)的羟基酯化形成果胶-熊果酸高分子，所述果胶酯化度50～75％，果胶-熊果酸高分子再自组装形成纳米粒子PET-UA·NPs，自组装过程中通过包裹双氢青蒿素疏水药物或10-羟基喜树碱，形成PET-UA(DHA)·NPs或PET-UA(HCPT)·NPs，形成具有核壳结构的纳米粒子，具体制备步骤如下：
(1)将一定量的果胶(PET)与冰醋酸、乙酸酐和硫酸在冰浴下反应，然后升温至50℃，搅拌至溶液澄清，混合物旋蒸，乙醇洗至中性，冷冻干燥，得到乙酰化果胶粉末A；
(2)取一定量的步骤(1)中的果胶粉末A溶于二甲基亚砜DMSO，果胶粉末A与DMSO的固液比为1:20～1:50(g/ml)，加入激活剂1-(3-二甲氨基丙基)-3-乙基碳二亚胺盐酸盐(EDC)，催化剂4-二甲氨基吡啶(DMAP)，搅拌反应30～50h，得到反应混合液；
(3)向步骤(2)中得到的反应混合液中加入体积比为1:1乙醚/乙醇溶液沉淀，离心，多次洗涤，沉淀物透析，冷冻干燥，得到粉末B(PET-UA)；
(4)将步骤(3)中粉末B和双氢青蒿素或10-羟基喜树碱分别溶于二甲基亚砜，并滴入去离子水中，所得纳米粒子溶液透析，透析过程每6h换一次PBS液，冷冻干燥，得到所述纳米粒子PET-UA(DHA)·NPs和PET-UA(HCPT)·NPs。
2.如权利要求1所述的一种纳米粒子的制备方法，其特征在于，所述的UA与EDC、DMAP的摩尔比为1:0.8:0.2，高分子PET-UA与DHA和HCPT的摩尔比分别为(1:0.5)～(1:1)和(1:0.1)～(1:2)。
3.如权利要求1所述的一种纳米粒子的制备方法，其特征在于，其纳米粒子中UA的载药量为0.1％-12％，纳米粒子半径10-200nm。
4.根据权利要求1所述的一种纳米粒子的制备方法所得到的纳米粒子，具有缓释功能、癌靶向性及稳定的粒径大小。
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| Synthesis, characterization, and in vitro and in vivo evaluation of a novel pectin-adriamycin conjugate;Xiao-Hai Tang等;《Bioorganic & Medicinal Chemistry》;20100107;第18卷(第4期);摘要和示意图1，第2.1.2小节、第2.4小节，图4 |
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