CN105754316A - 一种高强度超分子水凝胶及其制备方法 - Google Patents
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Abstract
本发明属于生物高分子材料技术领域。本发明提供了一种高强度超分子水凝胶及其制备方法。所述水凝胶由端基为单糖的聚乙二醇和α环糊精制备而成，其中聚乙二醇端基单糖之间的糖糖作用形成了第二个交联网络。采用端基修饰单糖的聚乙二醇和α?环糊精制备高强度的水凝胶，并将单糖修饰聚乙二醇低温处理增强糖糖相互作用，本发明制备的凝胶相对于文献中报道的其它PPR凝胶具有更高的强度。所述制备方法操作简单，所用聚合物易于合成，所制得水凝胶具有剪切变稀特性，可作为抗癌药物的可控缓释载体。
Description
技术领域
本发明属于生物高分子材料技术领域，尤其涉及一种高强度超分子水凝胶及其的制备方法。
背景技术
α-环糊精(α-cyclodextrins，α-CD)是一类由6个D-吡喃葡萄糖单元通过α-1,4糖苷键首尾连接而成的大环化合物。α-CD作为一种客体分子其能够和聚乙二醇(PEG)通过超分子作用形成准聚轮烷(PPR)水凝胶。其原理为PEG穿过α-CDs的空腔形成准聚轮烷，在疏水作用下α-CD可以进一步结晶形成物理交联点。由于α-CD结晶微区的物理交联点在外力作用下会发生解离，因此PPR凝胶具备剪切变稀特性，可以通过注射器将PPR凝胶注射到活体的皮下易于，这一特性使其在药物缓释方面得到了广泛的应用。同时PEG和α-CD均具有良好的生物相容性使PPR凝胶也具有无毒副作用的优点。但是PPR水凝胶中仅存在α-CD结晶形成的物理交联点使其强度相对较低，限制了其在药物缓释中的应用。针对此问题人们主要是通过在凝胶中引入纳米SiO2或黏土等无机材料增强其强度，虽然可以在一定程度增强其强度但是也增加了PPR水凝胶的生物毒性。
准聚轮烷(PPR)水凝胶用于药物缓释时，主要针对的是生物体，生物相容性尤其重要，最好不能具有生物毒性。由此可见，制备同时具备高强度和生物相容性的水凝胶，对其在生物和医药领域的推广应用有非常重要的意义。本发明通过引入天然存在的单糖来增强PPR水凝胶的强度，同时还保持PPR水凝胶的生物相容性。
发明内容
鉴于现有技术中存在上述技术问题，本发明提供了一种高强度超分子水凝胶及其制备方法，所述水凝胶中，除了超分子作用形成的第一个交联网络，聚乙二醇(PEG-Sugar)的端基单糖之间形成了第二个交联网络，使水凝胶同时具有良好的生物相容性和强度，尤其是无生物毒性。本发明采用的技术方案如下所述。
本发明提供一种高强度超分子水凝胶，所述水凝胶由端基为单糖的聚乙二醇(PEG-Sugar)和α环糊精(α-CD)制备而成，其中端基为单糖的聚乙二醇(PEG-Sugar)之间的糖糖作用形成了第二个交联网络。
上述端基为单糖的聚乙二醇(PEG-Sugar)包括三种，是端基分别为半乳糖、葡萄糖和甘露糖的聚乙二醇PEG-Gal、PEG-Glc和PEG-Man，其中聚乙二醇的重复单元数n为100-1000。三种聚乙二醇的分子式如下：
所述高强度超分子水凝胶中具有两个交联网络结构，一是聚乙二醇穿过α环糊精的空腔形成准聚轮烷，在疏水作用下α环糊精结晶形成的物理交联点；二是聚乙二醇的单糖端基之间通过糖糖作用形成的第二个交联点。
交联点的增多，大大增强了水凝胶的储能模量，同时单糖结构不具备生物毒性，不影响水凝胶的生物相容性。同时，由于第二交联点本质上还是一种物理交联点，并不会影响水凝胶的剪切变稀作用。由此可见，本发明扩大了水凝胶材料在药物缓释领域的应用范围，为开发新型PPR凝胶药物载体材料，实现对抗癌药物的缓释做出贡献。
本发明还提供上述高强度超分子水凝胶的制备方法，其具体步骤为：
(1)将端基为单糖的聚乙二醇(PEG-Sugar)水溶液冷冻处理一段时间，溶化后使用；
(2)将处理过的α环糊精(α-CD)水溶液加入到PEG-Sugar水溶液中搅拌混合均匀，经超声处理即可得到水凝胶。
所述端基为单糖的聚乙二醇(PEG-Sugar)包括三种，是端基分别为半乳糖、葡萄糖和甘露糖的聚乙二醇PEG-Gal、PEG-Glc和PEG-Man，聚乙二醇的重复单元数n为100-1000，三种聚乙二醇的分子式如下：
所述的PEG-Sugar是PEG-Gal、PEG-Glc和PEG-Man的一种或多种。
所述的PEG-Sugar水溶液的质量分数为100～400mg/mL。
所述的α-CD水溶液的质量分数为100～400mg/mL。
所述PEG-Sugar水溶液和α-CD水溶液的体积比为1:2～2:1。
所述低温环境温度为-80～-20℃。
所述低温处理时间12～48h。
上述方法操作简单，并制备了高强度的PEG-环糊精PPR水凝胶，从而扩大PPR水凝胶在各类抗癌药物可控释放中的应用范围。
本发明具有如下有益效果：1、所制得的水凝胶具有高强度、高生物相容性的优点，同时还保持了剪切变稀特性；2、所述水凝胶的制备方法操作简单，原料容易得到，成本低廉；3、为开发新型PPR凝胶药物载体材料，实现对抗癌药物的缓释做出贡献。
附图说明
图1为本发明实施例1、2、3和对比例所制备的水凝胶的外观图；
图2为本发明实施例1所制备的水凝胶的扫描电镜图；
图3为本发明实施例2所制备的水凝胶的储能模量曲线。
具体实施方式
下面结合具体实施例和附图来说明本发明的技术方案。
本发明所述高强度超分子水凝胶由端基为单糖的聚乙二醇(PEG-Sugar)和α环糊精(α-CD)制备而成，其中端基为单糖的聚乙二醇(PEG-Sugar)之间的糖糖作用形成了第二个交联网络。下面通过实施例1-10和对比例来说明本发明的制备方法。
对比例：
(1)将α-CD水溶液(1mL，100mg/mL)加入PEG水溶液(PEG重复单元数为100，1mL，100mg/mL)中，快速搅拌混合均匀，超声10min。
实施例1:
(1)将PEG-Gal水溶液(PEG重复单元数为100，1mL，100mg/mL)经-80℃冷冻处理24h；
(2)将α-CD水溶液(1mL，100mg/mL)加入处理过的PEG-Gal水溶液中，快速搅拌混合均匀，超声10min即可得到水凝胶。
图1为本发明实施例1所制备的水凝胶的扫描电镜图，有图可知水凝胶形成了有序的三维网络结构，且存在空洞可以用于负载药物。
实施例2:
(1)将PEG-Glc水溶液(PEG重复单元数为100，1mL，100mg/mL)经-80℃冷冻处理24h；
(2)将α-CD水溶液(1mL，100mg/mL)加入到处理过的PEG-Man水溶液中，快速搅拌混合均匀，超声10min即可得到水凝胶。
图3为本发明实施例2所制备的水凝胶的储能模量曲线，可见本实施例制得的水凝胶的储能强度远远大于普通PEG-PPR凝胶的储能强度。
实施例3:
(1)将PEG-Man水溶液(PEG重复单元数为100，1mL，100mg/mL)经-80℃冷冻处理24h；
(2)将α-CD水溶液(1mL，100mg/mL)加入到处理过的PEG-Glc水溶液中，快速搅拌混合均匀，超声10min即可得到水凝胶。
图1为本发明实施例1、2、3和对比例所制备的水凝胶的外观图，从图中可知相同条件下，纯聚乙二醇与α环糊精无法形成水凝胶，而PEG-Gal、PEG-Glc和PEG-Man与α环糊精可形成水凝胶。这是因为相同条件下，纯聚乙二醇与α环糊精之间形成的交联点无法维持其固态的形状，在自然状态下无法形成水凝胶，而PEG-Gal、PEG-Glc和PEG-Man还存在糖糖作用形成的第二种交联点，两种交联点的共同作用下，使得它们与α环糊精混合后形成水凝胶结构。
实施例4:
(1)将PEG-Gal水溶液(PEG重复单元数为1000，1mL，100mg/mL)经-40℃冷冻处理24h；
(2)将α-CD水溶液(1mL，400mg/mL)加入到处理过的PEG-Gal水溶液中，快速搅拌混合均匀，超声10min即可得到水凝胶。
实施例5:
(1)将PEG-Gal水溶液(PEG重复单元数为300，1mL，100mg/mL)经-20℃冷冻处理36h；
(2)将α-CD水溶液(1mL，100mg/mL)加入到处理过的PEG-Gal水溶液中，快速搅拌混合均匀，超声10min即可得到水凝胶。
实施例6:
(1)将PEG-Gal水溶液(PEG重复单元数为100，1mL，100mg/mL)经-80℃冷冻处理12h；
(2)将α-CD水溶液(1.5mL，200mg/mL)加入到处理过的PEG-Gal水溶液中，快速搅拌混合均匀，超声10min即可得到水凝胶。
实施例7：
(1)将PEG-Gal水溶液(PEG重复单元数为100，1mL，200mg/mL)经-20℃冷冻处理48h；
(2)将α-CD水溶液(1mL，200mg/mL)加入到处理过的PEG-Gal水溶液中，快速搅拌混合均匀，超声10min即可得到水凝胶。
实施例8:
(1)将PEG-Gal水溶液(PEG重复单元数为200，1mL，100mg/mL)经-20℃冷冻处理24h；
(2)将α-CD水溶液(2mL，100mg/mL)加入到处理过的PEG-Gal水溶液中，快速搅拌混合均匀，超声10min即可得到水凝胶。
实施例9:
(1)将PEG-Gal水溶液(PEG重复单元数为300，2mL，200mg/mL)经-80℃冷冻处理24h；
(2)将α-CD水溶液(1mL，100mg/mL)加入到处理过的PEG-Gal水溶液中，快速搅拌混合均匀，超声10min即可得到水凝胶。
实施例10:
(1)将PEG-Gal水溶液(PEG重复单元数为200，1.5mL，400mg/mL)经-80℃冷冻处理48h；
(2)将α-CD水溶液(1mL，100mg/mL)加入到处理过的PEG-Gal水溶液中，快速搅拌混合均匀，超声10min即可得到水凝胶。
Claims (10)
1.一种高强度超分子水凝胶，其特征在于，所述水凝胶由端基为单糖的聚乙二醇和α环糊精制备而成，其中聚乙二醇端基单糖的糖糖作用形成了第二个交联网络。
2.根据权利要求1所述的水凝胶，其特征在于，所述端基为单糖的聚乙二醇包括三种，是端基分别为半乳糖、葡萄糖和甘露糖的聚乙二醇，其中聚乙二醇的重复单元数n为100-1000，三种聚乙二醇的分子式如下：
3.一种如权利要求1或2所述的高强度超分子水凝胶的制备方法，其特征在于，具体步骤为：
(1)将端基为单糖的聚乙二醇水溶液冷冻处理一段时间，溶化后使用；
(2)将α环糊精水溶液加入到端基为单糖的聚乙二醇水溶液中搅拌混合均匀，经超声处理后即可得到水凝胶。
4.根据权利要求3所述的方法，其特征在于，所述端基为单糖的聚乙二醇包括三种，是端基分别为半乳糖、葡萄糖和甘露糖的聚乙二醇，其中聚乙二醇的重复单元数n为100-1000，三种聚乙二醇的分子式如下：分子式如下：
5.根据权利要求4中所述的方法，其特征在于，所述端基为单糖的聚乙二醇可以是上述三种聚合物中的一种或多种。
6.根据权利要求3中所述的方法，其特征在于，所述端基为单糖的聚乙二醇水溶液的质量分数为100～400mg/mL。
7.根据权利要求3中所述的方法，其特征在于，所述α环糊精水溶液的质量分数为100～400mg/mL。
8.根据权利要求3中所述的方法，其特征在于，所述端基为单糖的聚乙二醇水溶液和α环糊精水溶液的体积比为1:2～2:1。
9.根据权利要求3中所述的方法，其特征在于，步骤(1)中冷冻处理的温度为-80～-20℃。
10.根据权利要求3中所述的方法，其特征在于，步骤(1)中冷冻处理的时间为12～48h。
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| CN109734934A (zh) * | 2019-01-11 | 2019-05-10 | 闽江学院 | 一种纳米纤维素温敏凝胶的制备方法 |
| CN112142805A (zh) * | 2020-09-09 | 2020-12-29 | 江南大学 | 一种n-烷基葡萄糖胺小分子醇凝胶及其制备方法和应用 |
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| CN102827446A (zh) * | 2012-09-14 | 2012-12-19 | 武汉大学 | 一种温度响应型可注射水凝胶及其制备方法和用途 |
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| CN102827446A (zh) * | 2012-09-14 | 2012-12-19 | 武汉大学 | 一种温度响应型可注射水凝胶及其制备方法和用途 |
Non-Patent Citations (1)
| Title |
|---|
| JULIEN BABINOT，ET AL: ""Preparation of Clickable Poly(3-hydroxyalkanoate) (PHA): Application to Poly(ethylene glycol) (PEG) Graft Copolymers Synthesis"", 《MACROMOL. RAPID COMMUN.》 * |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN107376004A (zh) * | 2017-06-29 | 2017-11-24 | 广东泰宝医疗器械技术研究院有限公司 | 一种聚乙二醇医用敷料及其制备方法 |
| CN109734934A (zh) * | 2019-01-11 | 2019-05-10 | 闽江学院 | 一种纳米纤维素温敏凝胶的制备方法 |
| CN109734934B (zh) * | 2019-01-11 | 2021-11-02 | 闽江学院 | 一种纳米纤维素温敏凝胶的制备方法 |
| CN112142805A (zh) * | 2020-09-09 | 2020-12-29 | 江南大学 | 一种n-烷基葡萄糖胺小分子醇凝胶及其制备方法和应用 |
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