CN106750381A - 一种基于互穿网络结构的载四氧化三铁纳米水凝胶的制备方法 - Google Patents
一种基于互穿网络结构的载四氧化三铁纳米水凝胶的制备方法 Download PDFInfo
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Abstract
本发明涉及一种基于互穿网络结构的载四氧化三铁纳米水凝胶的制备方法，包括：将N‑异丙基丙烯酰胺、交联剂和乳化剂溶于去离子水中，氮气氛围下，搅拌，65～80℃保温，然后加入引发剂，继续反应0.5～4h，透析，得到PNIPAM；将交联剂加入到PNIPAM的水溶液中，氮气氛围下，搅拌，加入AA，搅拌，加入引发剂和催化剂，反应0.5～1.5h，透析，得到PNIPAM/PAA互穿网络结构纳米水凝胶；将Fe2+与Fe3+加入到纳米水凝胶中，室温下加入氨水，反应1～3h，透析，即得。本发明的工艺简单，原料易得，绿色环保；制备的磁性杂化凝胶在水介质中分散良好，在药物负载和控制释放等领域具有广阔前景。
Description
技术领域
本发明属于纳米水凝胶的制备领域，特别涉及一种基于互穿网络结构的载四氧化三铁纳米水凝胶的制备方法。
背景技术
水凝胶是指一类由物理或化学交联而形成，可以吸收大量水分并保持其三维结构的软物质。智能纳米水凝胶能响应环境信息，如温度、pH、磁、光等的微小变化，产生相应的体积变化，因此其在化学传感器、药物控释、物质分离等领域有重要的应用价值。其中，温度和pH作为两种重要的环境条件，受到外界关注。而最典型的制备温敏/pH响应性纳米水凝胶的单体为N-异丙基丙烯酰胺(NIPAM)与丙烯酸(AA)，例如Hu等人用PNIPAM与PAA制备具有互穿网络结构的纳米水凝胶，并研究其晶体的有序结构。(Hu Z,Xia X.HydrogelNanoparticle Dispersions with Inverse Thermoreversible Gelation.AdvancedMaterials,2004,16(4):305-309.)；Lai等研究了NIPAM与AA共聚纳米水凝胶的活性与稳定性。Lai E,Wang Y,Wei Y,et al.Covalent immobilization of trypsin onto thermo-sensitive poly(N-isopropylacrylamide-co-acrylic acid)microspHeres with highactivity and stability.Journal of Applied Polymer Science,2016,133(21)。
制备刺激响应性水凝胶的方法主要有无规共聚法，核壳结构法，互穿网络结构法。互穿聚合物网络是由2种或多种聚合物分子链相互贯穿或缠结形成三维网络结构。在互穿网络水凝胶中，聚合物之间没有化学键链接，各自保持着原有性能，同时，还产生特殊的协同作用，加快智能水凝胶的响应速率，在制备多重响应性水凝胶上受到学者的青睐。
近年来，磁性复合微球作为一种新型的功能高分子材料，由于兼具高分子微球的众多特性和磁响应性，受到广泛关注。常见的磁性粒子有Fe3O4,CrO2等金属氧化物以及CoFe2O4等铁酸盐类物质。由于Fe3O4纳米颗粒具有超顺磁性、高的磁化率以及良好的生物相容性，在生物医药应用方面受到学者们的青睐。然而，传统的Fe3O4磁性纳米颗粒由于其易聚集以及水相不兼容，限制其在各领域的应用，若将磁性纳米颗粒装载于聚合物微球中，不仅使其在水中具有良好分散性，复合微球还兼具超顺磁性，最终能广泛应用于药物靶向治疗、磁共振生物成像等生物领域。例如：Hariom Gupta等将Fe3O4装载于DHA中，并成功应用于磁共振成像。(Gupta H,Paul P,Kumar N,et al.One Pot Synthesis of Water-Dispersible DHA Coated Fe3O4Nanoparticles under AtmospHeric Air:Blood Cellcompatibility and Enhanced Magnetic Resonance Imaging.Journal of Colloid&Interface Science,2014.)，Malihe Kheirabadi等利用原位聚合将Fe3O4包载于hyaluronic acid中，并进行细胞毒性测试。Kheirabadi M,Shi L,Bagheri R,et al.Insitu forming interpenetrating hydrogels of hyaluronic acid hybridized withiron oxide nanoparticles.Biomaterials Science,2015,3(11):1466-1474.
发明内容
本发明所要解决的技术问题是提供一种基于互穿网络结构的载四氧化三铁纳米水凝胶的制备方法，该方法合成工艺简单易行、绿色环保；最终产物同时具有pH/温度/磁三重响应性，能在水中稳定存在，在水介质中分散良好；并且，该复合纳米凝胶的体积相转变温度(VPTT)不随亲水性单体的引入量以及磁性颗粒的增多而改变(改变量小于1℃)，始终维持在34℃，在药物负载和控制释放等领域具有广阔前景。
本发明的一种基于互穿网络结构的载四氧化三铁纳米水凝胶的制备方法，包括：
(1)将单体N-异丙基丙烯酰胺NIPAM、交联剂和乳化剂溶于去离子水中，氮气氛围下，搅拌，65～80℃保温30～50min，然后加入引发剂，继续反应0.5～4h，透析，得到聚N-异丙基丙烯酰胺PNIPAM；
(2)将交联剂加入到步骤(1)中PNIPAM的水溶液中，氮气氛围下，搅拌，冰浴条件下加入单体丙烯酸AA，搅拌，加入引发剂和催化剂，反应0.5～1.5h，透析，得到PNIPAM/PAA互穿网络结构纳米水凝胶；其中，PNIPAM与AA的质量比为100：2～20；
(3)将Fe2+与Fe3+加入到步骤(2)中PNIPAM/PAA互穿网络结构纳米水凝胶中，搅拌3～12h，室温下加入氨水，反应1～3h，透析，得到基于互穿网络结构的载四氧化三铁纳米水凝胶(载有Fe3O4的磁性纳米凝胶)；其中，Fe3+与PNIPAM/PAA互穿网络结构纳米水凝胶的质量比为0.01～0.8：100，Fe3+与Fe2+的质量比为0.01g～0.3g:0.0037g～0.11g。
所述Fe2+与Fe3+的来源优选为FeCl2·4H2O和FeCl3·6H2O。
所述步骤(1)中N-异丙基丙烯酰胺、交联剂、乳化剂和引发剂的质量比为100：1～3：2～5：3～6。
所述交联剂为N,N'-甲叉双丙烯酰胺MBA；乳化剂为十二烷基硫酸钠SDS；引发剂为过硫酸铵APS。
所述步骤(2)中PNIPAM的水溶液的质量浓度为1.36％。
所述步骤(2)中AA、交联剂、引发剂和催化剂的质量比为100：10～30：3～6：3～6。
所述交联剂为N,N'-甲叉双丙烯酰胺MBA；引发剂为过硫酸铵APS；催化剂为焦亚硫酸钠Na2S2O5。
所述步骤(3)中氨水浓度为25-30wt％，氨水与Fe3+的质量比为(0.01～0.3g：1～5g)。
所述氨水的用量为1～5g。
所述步骤(1)、步骤(2)和步骤(3)中透析的条件为：采用超纯水浸泡3-7天，每天换3次水；所用透析袋的截留分子量为8000-14000。
所述步骤(3)中基于互穿网络结构的载四氧化三铁纳米水凝胶的粒径为230～565nm。
本发明以制备温敏性高分子聚(异丙基丙烯酰胺)(PNIPAM)的单体异丙基丙烯酰胺(NIPAM)为单体，以亲水性的丙烯酸(AA)为功能单体，采用乳液聚合的方法，实现调节体积pH相转变的智能性。
本发明利用亲水性单体AA在碱性条件下，电离出COO-的特点，将铁离子与其络合作用引入IPN结构纳米水凝胶中，通过原位聚合，铁离子与氨水作用生成Fe3O4，成功制备载有Fe3O4的磁性纳米水凝胶。
有益效果
(1)本发明采用的方法工艺简单，原料易得，绿色环保，制备所得的互穿网络结构(IPN)纳米水凝胶，不仅比传统的PNIPAM有更良好的生物相容性，同时亲水性单体AA的加入赋予了纳米水凝胶pH敏感性；
(2)本发明将Fe3O4通过原位聚合载入互穿网络结构纳米水凝胶中，赋予纳米水凝胶磁性性能，在药物控释，蛋白质分离等领域有很大应用前景；
(3)本发明制备的复合纳米水凝胶，同时具备pH/温度/磁性三重响应性，其中，改变任一组成成分的用量，例如AA或Fe3O4，均不影响复合纳米水凝胶的体积相转变温度，始终保持在34℃左右，与人体温度相似，使其在生物医学有很大应用前景，尤其用于体内癌症治疗，药物传输等方面。
附图说明
图1是实施例2中载有Fe3O4的互穿网络结构纳米水凝胶XRD图；
图2是实施例2中载有Fe3O4的互穿网络结构纳米水凝胶的体积相转变的UV-vis图；
图3是实施例2中载有Fe3O4的互穿网络结构纳米水凝胶的pH响应性粒径图；
图4是实施例1,2,3中载有Fe3O4的互穿网络结构纳米水凝胶磁吸附图；其中，A，B，C分别代表实施例1、实施例2和实施例3。
具体实施方式
下面结合具体实施例，进一步阐述本发明。应理解，这些实施例仅用于说明本发明而不用于限制本发明的范围。此外应理解，在阅读了本发明讲授的内容之后，本领域技术人员可以对本发明作各种改动或修改，这些等价形式同样落于本申请所附权利要求书所限定的范围。
实施例1
取1.9027g NIPAM、0.0355g MBA、0.076g SDS溶于140ml去离子水中，并于室温下鼓入N2除氧，磁力搅拌100分钟；反应温度升至70℃，并在N2保护下保温30分钟；
然后将0.083g引发剂APS溶于10ml去离子水，加入上述溶液中，保持N2气氛，继续反应4小时；然后把所得反应物浸泡于去离子水中透析7天，每天换三次水，去除残留反应原料及反应体系中电解质；所用透析袋截留分子量为8000～14000，即得PNIPAM。
取15ml PNIPAM溶液，稀释十倍，加入0.3203g MBA，N2保护下磁力搅拌30min；冰浴下加入1.523g AA，磁力搅拌20min；然后将0.1023g APS和0.1023g Na2S2O5分别溶于5ml去离子水，依次加入上述溶液，保持氮气氛围，持续反应40min；
然后把所得反应物浸泡于去离子水中透析7天，每天换三次水，去除残留反应原料及反应体系中电解质；所用透析袋截留分子量为8000～14000，即得PNIPAM/PAA互穿网络纳米水凝胶(IPN结构纳米水凝胶)。
取50g IPN结构纳米水凝胶，室温下加入0.0288g Fe3+，N2保护下机械搅拌4h；加入0.086g Fe2+，N2保护下机械搅拌30min；然后加入3g氨水(25wt％)，保持氮气氛围，持续反应3h；然后把所得反应物浸泡于去离子水中透析7天，每天换三次水，去除残留反应原料及反应体系中电解质。所用透析袋截留分子量为8000～14000。即得载有Fe3O4的互穿网络结构纳米水凝胶。
实施例2
取1.9027g NIPAM、0.0355g MBA、0.076g SDS溶于140ml去离子水中，并于室温下鼓入N2除氧，磁力搅拌100分钟；反应温度升至70℃，并在N2保护下保温30分钟；
然后将0.083g引发剂APS溶于10ml去离子水，加入上述溶液中，保持N2气氛，继续反应4小时；然后把所得反应物浸泡于去离子水中透析7天，每天换三次水，去除残留反应原料及反应体系中电解质。所用透析袋截留分子量为8000～14000。即得PNIPAM。
取15ml PNIPAM溶液，稀释十倍，加入0.3203g MBA，N2保护下磁力搅拌30min；冰浴下加入2.5043g AA，磁力搅拌20min；然后将0.1023g APS和0.1023g Na2S2O5分别溶于5ml去离子水，依次加入上述溶液，保持氮气氛围，持续反应40min；然后把所得反应物浸泡于去离子水中透析7天，每天换三次水，去除残留反应原料及反应体系中电解质。所用透析袋截留分子量为8000～14000。即得PNIPAM/PAA互穿网络纳米水凝胶(IPN结构纳米水凝胶)。
取50g IPN结构纳米水凝胶，室温下加入0.0288g Fe3+，N2保护下机械搅拌4h；加入0.086g Fe2+，N2保护下机械搅拌30min；然后加入3g氨水(25wt％)，保持氮气氛围，持续反应3h；然后把所得反应物浸泡于去离子水中透析7天，每天换三次水，去除残留反应原料及反应体系中电解质。所用透析袋截留分子量为8000～14000。即得载有Fe3O4的互穿网络结构纳米水凝胶。
实施例3
取1.9027g NIPAM、0.0355g MBA、0.076g SDS溶于140ml去离子水中，并于室温下鼓入N2除氧，磁力搅拌100分钟；反应温度升至70℃，并在N2保护下保温30分钟；
然后将0.083g引发剂APS溶于10ml去离子水，加入上述溶液中，保持N2气氛，继续反应4小时；然后把所得反应物浸泡于去离子水中透析7天，每天换三次水，去除残留反应原料及反应体系中电解质。所用透析袋截留分子量为8000～14000。即得PNIPAM。
取15ml PNIPAM溶液，稀释十倍，加入0.3203g MBA，N2保护下磁力搅拌30min；冰浴下加入1.523g AA，磁力搅拌20min；然后将0.1023g APS和0.1023g Na2S2O5分别溶于5ml去离子水，依次加入上述溶液，保持氮气氛围，持续反应40min；然后把所得反应物浸泡于去离子水中透析7天，每天换三次水，去除残留反应原料及反应体系中电解质。所用透析袋截留分子量为8000～14000。即得PNIPAM/PAA互穿网络纳米水凝胶(IPN结构纳米水凝胶)。
取50g IPN结构纳米水凝胶，室温下加入0.0553g Fe3+，N2保护下机械搅拌4h；加入0.0184g Fe2+，N2保护下机械搅拌30min；然后加入3g氨水(25wt％)，保持氮气氛围，持续反应3h；然后把所得反应物浸泡于去离子水中透析7天，每天换三次水，去除残留反应原料及反应体系中电解质。所用透析袋截留分子量为8000～14000。即得载有Fe3O4的互穿网络结构纳米水凝胶。
Claims (9)
1.一种基于互穿网络结构的载四氧化三铁纳米水凝胶的制备方法，包括：
(1)将单体N-异丙基丙烯酰胺NIPAM、交联剂和乳化剂溶于去离子水中，氮气氛围下，搅拌，65～80℃保温30～50min，然后加入引发剂，继续反应0.5～4h，透析，得到聚N-异丙基丙烯酰胺PNIPAM；
(2)将交联剂加入到步骤(1)中PNIPAM的水溶液中，氮气氛围下，搅拌，加入单体丙烯酸AA，搅拌，加入引发剂和催化剂，反应0.5～1.5h，透析，得到PNIPAM/PAA互穿网络结构纳米水凝胶；其中，PNIPAM与AA的质量比为100：2～20；
(3)将Fe2+与Fe3+加入到步骤(2)中PNIPAM/PAA互穿网络结构纳米水凝胶中，室温下加入氨水，反应1～3h，透析，得到基于互穿网络结构的载四氧化三铁纳米水凝胶；其中，Fe3+与PNIPAM/PAA互穿网络结构纳米水凝胶的质量比为0.01～0.8：100，Fe3+与Fe2+的质量比为0.01～0.3：0.0037～0.11。
2.根据权利要求1所述的一种基于互穿网络结构的载四氧化三铁纳米水凝胶的制备方法，其特征在于，所述步骤(1)中N-异丙基丙烯酰胺、交联剂、乳化剂和引发剂的质量比为100：1～3：2～5：3～6。
3.根据权利要求2所述的一种基于互穿网络结构的载四氧化三铁纳米水凝胶的制备方法，其特征在于，所述交联剂为N,N'-甲叉双丙烯酰胺MBA；乳化剂为十二烷基硫酸钠SDS；引发剂为过硫酸铵APS。
4.根据权利要求1所述的一种基于互穿网络结构的载四氧化三铁纳米水凝胶的制备方法，其特征在于，所述步骤(2)中PNIPAM的水溶液的质量浓度为1.36％。
5.根据权利要求1所述的一种基于互穿网络结构的载四氧化三铁纳米水凝胶的制备方法，其特征在于，所述步骤(2)中AA、交联剂、引发剂和催化剂的质量比为100：10～30：3～6：3～6。
6.根据权利要求5所述的一种基于互穿网络结构的载四氧化三铁纳米水凝胶的制备方法，其特征在于，所述交联剂为N,N'-甲叉双丙烯酰胺MBA；引发剂为过硫酸铵APS；催化剂为焦亚硫酸钠Na2S2O5。
7.根据权利要求1所述的一种基于互穿网络结构的载四氧化三铁纳米水凝胶的制备方法，其特征在于，所述步骤(3)中氨水浓度为25-30wt％，氨水与Fe3+的质量比为0.01～0.3：1～5。
8.根据权利要求1所述的一种基于互穿网络结构的载四氧化三铁纳米水凝胶的制备方法，其特征在于，所述步骤(1)、步骤(2)和步骤(3)中透析的条件为：采用超纯水浸泡3-7天，每天换3次水；所用透析袋的截留分子量为8000-14000。
9.根据权利要求1所述的一种基于互穿网络结构的载四氧化三铁纳米水凝胶的制备方法，其特征在于，所述步骤(3)中基于互穿网络结构的载四氧化三铁纳米水凝胶的粒径为230～565nm。
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| CN108084624B (zh) * | 2018-01-05 | 2019-09-27 | 东华大学 | 一种具有缺陷的响应性光子晶体的制备方法 |
| CN111378068A (zh) * | 2018-12-29 | 2020-07-07 | 武夷学院 | 一种基于限进介质的磁性温敏分子印迹互穿聚合物网络的制备方法 |
| CN111378068B (zh) * | 2018-12-29 | 2022-04-05 | 武夷学院 | 一种基于限进介质的磁性温敏分子印迹互穿聚合物网络的制备方法 |
| CN109777017A (zh) * | 2019-01-30 | 2019-05-21 | 广东省石油与精细化工研究院 | 一种双网络磺化聚苯醚/丙烯酸脂类复合材料的制备方法 |
| CN109777017B (zh) * | 2019-01-30 | 2021-01-15 | 广东省石油与精细化工研究院 | 一种双网络磺化聚苯醚/丙烯酸脂类复合材料的制备方法 |
| CN109897198A (zh) * | 2019-03-12 | 2019-06-18 | 南京邮电大学 | 高机械性能的磁性纳米双网络复合水凝胶及其制备方法 |
| CN112831066A (zh) * | 2021-02-18 | 2021-05-25 | 四川大学 | 具有宽阈值和高灵敏的温敏光子晶体凝胶及制备方法 |
| CN112831066B (zh) * | 2021-02-18 | 2021-11-30 | 四川大学 | 具有宽阈值和高灵敏的温敏光子晶体凝胶及制备方法 |
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