CN110358007B - 一种基于金属锌有机框架水凝胶、制备方法及应用 - Google Patents
一种基于金属锌有机框架水凝胶、制备方法及应用 Download PDFInfo
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- CN110358007B CN110358007B CN201910573949.3A CN201910573949A CN110358007B CN 110358007 B CN110358007 B CN 110358007B CN 201910573949 A CN201910573949 A CN 201910573949A CN 110358007 B CN110358007 B CN 110358007B
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- hydrogel
- organic framework
- metal zinc
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Abstract
本发明公开了一种基于金属锌有机框架水凝胶、制备方法及应用,包括以下步骤:步骤1:将高分子单体和锌盐溶于水中形成混合溶液,聚合为水凝胶基体;其中,混合溶液中高分子单体的浓度为1~1000 mg/mL,锌离子浓度为1~1000 mg/mL;步骤2:将步骤1得到的水凝胶基体浸泡于有机配体溶液中,至少24 h后即得到所需水凝胶;有机配体溶液中有机配体的浓度为1~2000 mg/mL;本发明水凝胶中金属锌有机框架原位形成,克服了金属锌有机框架不溶于水,不能在水凝胶中均匀分散的问题,具有良好的机械强度;金属锌有机框架可将疏水性难溶药物包载于亲水性的水凝胶中,克服了疏水性难溶药物无法包载于水凝胶的问题。
Description
技术领域
本发明涉及一种基于金属锌有机框架水凝胶、制备方法及应用。
背景技术
在组织修复与再生中,药物治疗作为传统有效的治疗方法,仍有巨大的医疗价值。随着科技的发展,按需定点释放药物已成为目前的研究热点。但目前仍面临着疏水性药物不溶于水、难以包载并实现在特定的病理部位释放的问题。金属锌有机框架作为新兴的纳米材料,具有超高的孔隙度和比表面积、结构多样性及可设计性,在药物递送领域受到广泛关注。但是目前大多利用将金属有机框架直接加入水凝胶前驱体中聚合的方式,但是该方法制备的水凝胶内部金属有机框架分布不均匀,力学性能较差,包载药物效率低。
发明内容
本发明提供一种具有优异的载药率、生物相容性、能够负载疏水性难溶药物的基于金属锌有机框架水凝胶、制备方法及应用。
本发明采用的技术方案是:一种基于金属锌有机框架水凝胶的制备方法,包括以下步骤:
步骤1:将高分子单体和锌盐溶于水中形成混合溶液,聚合为水凝胶基体;其中,混合溶液中高分子单体的浓度为1~1000 mg/mL,锌离子浓度为1~1000 mg/mL;
步骤2:将步骤1得到的水凝胶基体浸泡于有机配体溶液中,至少24 h后即得到所需水凝胶;有机配体溶液中有机配体的浓度为1~2000 mg/mL。
进一步的,所述步骤1中高分子为:单体丙烯酸、N-异丙基丙烯酰胺、丙烯酰胺、3-(2-甲基丙烯酰氧乙基二甲胺基) 丙磺酸盐、甲基丙烯酸二甲氨基乙酯、聚乙二醇双丙烯酸酯、聚乙二醇二甲基丙烯酸酯、聚乙二醇,明胶,壳聚糖,纤维素、透明质酸、甲基纤维素、羧甲基纤维素、羟丙基甲基纤维素、羟乙基纤维素、甲壳素中的一种或两种及以上以任意配比构成。
进一步的,所述步骤1中的锌盐为醋酸锌或硝酸锌中的一种。
进一步的,所述步骤1混合溶液中加入引发剂、交联剂通过热聚合、光聚合或自凝胶的方法聚合为水凝胶基体;引发剂为过硫酸铵、过硫酸钾、偶氮二异丁腈、过氧化苯甲酰或叔丁基过氧化氢中的一种;交联剂为N, N-亚甲基双丙烯酰胺、聚乙二醇双丙烯酸酯、光引发剂2959、二甲基丙烯酸乙二醇酯或二氨基二苯基甲烷中的一种。
进一步的,所述步骤2中的有机配体为1,4-二氯咪唑、2-甲基咪唑中的一种。
一种基于金属锌有机框架水凝胶。
一种基于金属锌有机框架水凝胶作为载药基体的应用,所述步骤2中将步骤2得到的水凝胶基体浸泡于有机配体和药物构成的混合溶液得到包载药物的水凝胶;混合溶液中药物的浓度为1~2000 mg/mL;药物为蛇床子素、紫杉醇、阿霉素、达那唑中的一种或两种及以上以任意配比构成。
本发明的有益效果是:
(1)本发明金属锌有机框架在水凝胶内部原位形成,克服了金属锌有机框架不溶于水,不能在水凝胶中均匀分散的问题;
(2)本发明水凝胶中的金属锌有机框架,可对水凝胶的力学性质产生纳米增强的效果,使水凝胶具有良好的机械强度;
(3)本发明水凝胶中的金属锌有机框架,可将疏水性难溶药物包载于亲水性的水凝胶中,克服了疏水性难溶药物无法包载于水凝胶的问题。
附图说明
图1为本发明实施例7中得到的金属锌有机框架的载药水凝胶的SEM图。
图2为本发明实施例7中得到的金属锌有机框架的载药水凝胶的SEM图。
具体实施方式
下面结合附图和具体实施例对本发明做进一步说明。
实施例1
按照以下方法制备金属锌有机框架的载药水凝胶,包括以下步骤:
步骤1:将硝酸锌、丙烯酰胺溶于水中形成混合溶液,其中混合溶液中硝酸锌浓度为20 mg/mL,丙烯酰胺浓度为260 mg/mL;在混合溶液中加入占丙烯酰胺质量5%的引发剂过硫酸铵和占丙烯酰胺质量0.1%的交联剂甲叉丙烯酰胺,混合均匀,加入模具,在紫外灯下照射20 min,即聚合为水凝胶。
步骤2:将水凝胶在模具中取出,浸泡于1,4-二氯咪唑和紫杉醇的甲醇溶液中;其中甲醇溶液中1,4-二氯咪唑的浓度为250 mg/mL,紫杉醇的浓度为20 mg/mL;24小时后,即得到所需原位形成的金属锌有机框架的载药水凝胶。
实施例2
按照以下方法制备金属锌有机框架的载药水凝胶,包括以下步骤:
步骤1:将硝酸锌、丙烯酰胺和丙烯酸(丙烯酰胺和丙烯酸的质量比为1:1)溶于水中形成混合溶液,其中混合溶液中硝酸锌浓度为30 mg/mL,丙烯酰胺和丙烯酸的浓度为200mg/mL;在混合溶液中加入占丙烯酰胺和丙烯酸总质量4%的引发剂过硫酸钾和占丙烯酰胺和丙烯酸总质量0.1%的交联剂N,N-亚甲基丙烯酰胺,混合均匀,加入模具,在紫外灯下照射20 min,即聚合为水凝胶。
步骤2:将水凝胶在模具中取出,浸泡于1,4-二氯咪唑和蛇床子素的甲醇溶液中;其中甲醇溶液中1,4-二氯咪唑的浓度为250 mg/mL,蛇床子素的浓度为30 mg/mL;36小时后,即得到所需原位形成的金属锌有机框架的载药水凝胶。
实施例3
按照以下方法制备金属锌有机框架的载药水凝胶,包括以下步骤:
步骤1:将醋酸锌、N-异丙基丙烯酰胺溶于水中形成混合溶液,其中混合溶液中醋酸锌浓度为25 mg/mL,N-异丙基丙烯酰胺浓度为200 mg/mL;在混合溶液中加入占N-异丙基丙烯酰胺质量3%的引发剂过硫酸钾和占N-异丙基丙烯酰胺质量0.1%的交联剂甲叉丙烯酰胺,混合均匀,加入模具,在紫外灯下照射20 min,即聚合为水凝胶。
步骤2:将水凝胶在模具中取出,浸泡于2-甲基咪唑和阿霉素的甲醇溶液中;其中甲醇溶液中2-甲基咪唑的浓度为250 mg/mL,阿霉素的浓度为30 mg/mL;24小时后,即得到所需原位形成的金属锌有机框架的载药水凝胶。
实施例4
按照以下方法制备金属锌有机框架的载药水凝胶,包括以下步骤:
步骤1:将醋酸锌、聚乙烯醇溶于90 ℃水中形成混合溶液,其中混合溶液中醋酸锌浓度为20 mg/mL,聚乙烯醇浓度为220 mg/mL;混合均匀,加入模具,放入-20 ℃冰箱中6小时,室温熔化后,反复冻融5次,即聚合为水凝胶。
步骤2:将水凝胶在模具中取出,浸泡于1,4-二氯咪唑和达那唑的甲醇溶液中;其中甲醇溶液中1,4-二氯咪唑的浓度为100 mg/mL,达那唑的浓度为10 mg/mL;48小时后,即得到所需原位形成的金属锌有机框架的载药水凝胶。
实施例5
按照以下方法制备金属锌有机框架的载药水凝胶,包括以下步骤:
步骤1:将硝酸锌、3-(2-甲基丙烯酰氧乙基二甲胺基) 丙磺酸盐溶于水中形成混合溶液,其中混合溶液中硝酸锌浓度为25 mg/mL,3-(2-甲基丙烯酰氧乙基二甲胺基) 丙磺酸盐浓度为200 mg/mL;在混合溶液中加入占3-(2-甲基丙烯酰氧乙基二甲胺基) 丙磺酸盐质量1%的引发剂I 2959和占3-(2-甲基丙烯酰氧乙基二甲胺基) 丙磺酸盐质量0.1%的交联剂甲叉丙烯酰胺,混合均匀,加入模具,在紫外灯下照射20 min,即聚合为水凝胶。
步骤2:将水凝胶在模具中取出,浸泡于2-甲基咪唑和达那唑的甲醇溶液中;其中甲醇溶液中2-甲基咪唑的浓度为90 mg/mL,达那唑的浓度为30 mg/mL;48小时后,即得到所需原位形成的金属锌有机框架的载药水凝胶。
实施例6
按照以下方法制备金属锌有机框架的载药水凝胶,包括以下步骤:
步骤1:将硝酸锌、丙烯酸溶于水中形成混合溶液,其中混合溶液中硝酸锌浓度为40 mg/mL,丙烯酸浓度为200 mg/mL;在混合溶液中加入占丙烯酸质量5%的引发剂过硫酸钠和占丙烯酸质量0.1%的交联剂N-异丙基丙烯酰胺,混合均匀,加入模具,在紫外灯下照射18min,即聚合为水凝胶。
步骤2:将水凝胶在模具中取出,浸泡于1,4-二氯咪唑和蛇床子素的甲醇溶液中;其中甲醇溶液中1,4-二氯咪唑的浓度为200 mg/mL,蛇床子素的浓度为10 mg/mL;24小时后,即得到所需原位形成的金属锌有机框架的载药水凝胶。
实施例7
按照以下方法制备金属锌有机框架的载药水凝胶,包括以下步骤:
步骤1:将硝酸锌、丙烯酸、3-(2-甲基丙烯酰氧乙基二甲胺基) 丙磺酸盐溶于水中形成混合溶液,其中混合溶液中硝酸锌浓度为40 mg/mL,丙烯酸浓度为50 mg/mL,3-(2-甲基丙烯酰氧乙基二甲胺基) 丙磺酸盐浓度为200 mg/mL;在混合溶液中加入占丙烯酸和3-(2-甲基丙烯酰氧乙基二甲胺基) 丙磺酸盐总质量5%的光引发剂I 2959和占丙烯酸和3-(2-甲基丙烯酰氧乙基二甲胺基) 丙磺酸盐总质量0.1%的交联剂N-异丙基丙烯酰胺,混合均匀,加入模具,在紫外灯下照射15 min,即聚合为水凝胶。
步骤2:将水凝胶在模具中取出,浸泡于1,4-二氯咪唑和蛇床子素的甲醇溶液中;其中甲醇溶液中1,4-二氯咪唑的浓度为220 mg/mL,蛇床子素的浓度为18 mg/mL;24小时后,即得到所需原位形成的金属锌有机框架的载药水凝胶。
本实施例制备得到的金属锌有机框架的载药水凝胶SEM图如图1和图2所示,从图中可以看出水凝胶内分布着规则形状的金属锌有机框架(图2 为图1 的孔壁的放大图)。
本发明中的金属锌有机框架在水凝胶中原位形成,克服了金属锌有机框架不溶于水,不能在水凝胶中均匀分散的缺点;金属锌有机框架对水凝胶的力学性质产生纳米增强的效果,使水凝胶具有良好的机械强度;并且金属锌有机框架,可将疏水性难溶药物包载于亲水性的水凝胶中,克服了疏水性难溶药物无法包载于水凝胶的难题。
Claims (7)
1.一种基于金属锌有机框架水凝胶的制备方法,其特征在于,包括以下步骤:
步骤 1:将高分子单体和锌盐溶于水中形成混合溶液,聚合为水凝胶基体;其中,混合溶液中高分子单体的浓度为200~260mg/mL,锌离子浓度为 20~40mg/mL;
步骤 2:将步骤 1 得到的水凝胶基体浸泡于有机配体溶液中,至少 24 h 后即得到所需水凝胶;有机配体溶液中有机配体的浓度为90~250 mg/mL。
2.根据权利要求 1 所述的一种基于金属锌有机框架水凝胶的制备方法,其特征在于,所述步骤 1中高分子为:单体丙烯酸、N-异丙基丙烯酰胺、丙烯酰胺、3-(2-甲基丙烯酰氧乙基 二甲胺基) 丙磺酸盐中的一种或两种以任意配比构成。
3. 根据权利要求 1 所述的一种基于金属锌有机框架水凝胶的制备方法,其特征在于,所述步骤 1中的锌盐为醋酸锌或硝酸锌中的一种。
4. 根据权利要求 1 所述的一种基于金属锌有机框架水凝胶的制备方法,其特征在于,所述步骤 1 混合溶液中加入引发剂、交联剂通过光聚合的方法聚合为水凝胶基体;引发剂为过硫酸铵、过硫酸钾、偶氮二异丁腈、过氧化苯甲酰或叔丁基过氧化氢中的一种;交联剂为 N, N-亚甲基双丙烯酰胺中的一种。
5.根据权利要求 1 所述的一种基于金属锌有机框架水凝胶的制备方法,其特征在于,所述步骤 2 中的有机配体为 1,4-二氯咪唑、2-甲基咪唑中的一种。
6.如权利要求 1~5 任一项制备方法得到的一种基于金属锌有机框架水凝胶。
7.如权利要求 1~5 任一项制备方法得到的一种基于金属锌有机框架水凝胶作为载药基体的应用,其特征在于,所述步骤 2 中将步骤 2 得到的水凝胶基体浸泡于有机配体和药物构成的混合溶液得到包载药物的水凝胶;混合溶液中药物的浓度为 10~30 mg/mL;药物为蛇床子素、紫杉醇、阿霉素、达那唑中的一种或两种以任意配比构成。
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