光聚合型pH敏感水凝胶的制备及药物缓释性能
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摘要
以四臂聚乙二醇(4-arm-PEG,M_n=4000)、ε-己内酯(ε-CL)及丙烯酰氯(AC)为原料合成了大分子单体4-arm-PEG-PCL-AC,在紫外光照射及光引发剂作用下与单体甲基丙烯酸(MAA)共聚交联制备了可生物降解、pH敏感水凝胶。通过红外光谱、核磁共振对大分子单体的结构进行了表征,使用扫描电子显微镜对干胶的微观形态进行观察,并对水凝胶的溶胀、体外降解及药物缓释性能进行了系统的研究。实验结果表明,随着水凝胶中MAA含量的增加及缓冲介质pH值的升高,水凝胶的pH敏感性增强,溶胀率增大;药物释放速率及释放量随pH值的升高而增加;在pH=7.4时,MAA含量越大,水凝胶的药物缓释速率及降解速率越快。该类型的pH敏感水凝胶具有良好的生物相容性、pH敏感性及降解、药物缓释可控性,可应用于药物传送系统,提高水凝胶应用于生物医疗领域时的功能性及疗效。
In this paper, a novel biodegradable pH sensitive hydrogel was prepared by ultraviolet-induced free radical polymerization using 4-arm-poly(ethylene glycol)-poly(ε-caprolactone)-acrylate(4-arm-PEG-PCL-AC) and methacrylic acid(MAA) as crosslinking monomer. The chemical structure of the macromonomer was characterized by IR and ~1H-NMR. The morphologies of the dried pH sensitive hydrogels were observed by scanning electron microscope, and the swelling ratio, in vitro degradation and drug release properties of the hydrogels were systematically studied. The results show that the pH sensitivity, equilibrium swelling ratio, drug release rate increase with the increment of medium pH value, and the pH sensitivity and equilibrium swelling ratio also increase with the increment of MAA content in hydrogel. At pH=7.4, the drug release rate and in vitro degradation rate increase with the increment of MAA content. The pH sensitive hydrogels possess a good biocompatibility, pH sensitivity, biodegradability and controlled drug release, which allow it to be used in drug delivery system and improve the application of hydrogels in biomedical field.
In this paper, a novel biodegradable pH sensitive hydrogel was prepared by ultraviolet-induced free radical polymerization using 4-arm-poly(ethylene glycol)-poly(ε-caprolactone)-acrylate(4-arm-PEG-PCL-AC) and methacrylic acid(MAA) as crosslinking monomer. The chemical structure of the macromonomer was characterized by IR and ~1H-NMR. The morphologies of the dried pH sensitive hydrogels were observed by scanning electron microscope, and the swelling ratio, in vitro degradation and drug release properties of the hydrogels were systematically studied. The results show that the pH sensitivity, equilibrium swelling ratio, drug release rate increase with the increment of medium pH value, and the pH sensitivity and equilibrium swelling ratio also increase with the increment of MAA content in hydrogel. At pH=7.4, the drug release rate and in vitro degradation rate increase with the increment of MAA content. The pH sensitive hydrogels possess a good biocompatibility, pH sensitivity, biodegradability and controlled drug release, which allow it to be used in drug delivery system and improve the application of hydrogels in biomedical field.
引文
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[18] 彭辉,罗彦凤,孙姣霞,等.新型可生物降解两性pH敏感水凝胶的制备与性能研究[J].材料导报,2010,24(14):48-51.Peng H,Luo Y F,Sun J X,et al.Synthesis and characterization of a novel biodegradable amphoteric pH-sensitive hydrogel [J].Materials Review,2010,24(14):48-51.
[19] Zhen W,Zhu Y,Wang W,et al.Synthesis and properties of amphipathic poly(D,L-lactide-co-glycolide)-polyethylene glycol-poly(D,L-lactide-co-glycolide) triblock copolymers[J].Aust.J.Chem.,2015,68:1593-1598.
[2] 李艳丽.生物高分子水凝胶的制备与表征[D].南京:东南大学,2016.Li Y L.The preparation and characterization of biopolymer hydrogels[D].Nanjing:Dissertation for Doctoral Degree of Southeast University,2016.
[3] 潘玉妹,徐坚,陈强,等.智能水凝胶在生物载药领域的研究进展[J].化工进展,2016,35(S1):202-208.Pan Y M,Xu J,Chen Q,et al.Research progress of intelligent hydrogels in biological drug carrying[J].Chemical Industry and Engineering Progress,2016,35(S1):202-208.
[4] Bai H,Li C,Wang X,et al.A pH-sensitive graphene oxide composite hydrogel [J].Chem.Commun.,2010,46:2376-2378.
[5] 李钒,张金龙,尹玉姬.生物医用高强度水凝胶的研究进展[J].化工进展,2012,31(11):2511-2519.Li F,Zhang J L,Yin Y J.Research progress of high mechanical strength hydrogels for biomedical application [J].Chemical Industry and Engineering Progress,2012,31(11):2511-2519.
[6] Nesrinne S,Djamel A.Synthesis,characterization and rheological behavior of pH sensitive poly(acrylamide-co-acrylic acid) hydrogels [J].Arab.J.Chem.,2017,50:1916-1918.
[7] Gao C,Ren J,Zhao C,et al.Xylan-based temperature/pH sensitive hydrogels for drug controlled release[J].Carbohydr.Polym.,2016,151:189-197.
[8] Rizwan M,Yahya R,Hassan A,et al.pH sensitive hydrogels in drug delivery:brief history,properties,swelling,and release mechanism,material selection and applications [J].Polymers,2017,9:DOI:10.3390/polym9040137.
[9] Gattás-Asfura K M,Zheng Y J,Micic M,et al.Immobilization of quantum dots in the photo-cross-linked poly(ethylene glycol)-based hydrogel [J].J.Phys.Chem.B,2003,107:10464-10469.
[10] Jain E,Hill L,Canning E,et al.Control of gelation,degradation and physical properties of polyethylene glycol hydrogels through the chemical and physical identity of the crosslinker [J].J.Mater.Chem.B,2017,5:2679-2691.
[11] Zheng Y J,Gattás-Asfura K M,Li C Q,et al.Design of a membrane fluorescent sensor based on photo-cross-linked PEG hydrogel [J].J.Phys.Chem.,B,2003,107:483-488.
[12] Wu D Q,Sun Y X,Xu X D,et al.Biodegradable and pH-sensitive hydrogels for cell encapsulation and controlled drug release [J].Biomacromolecules,2008,9:1155-1162.
[13] Tally M,Atassi Y.Synthesis and characterization of pH-sensitive superabsorbent hydrogels based on sodium alginate-g -poly(acrylic acid-co-acrylamide) obtained via an anionic surfactant micelle templating under microwave irradiation [J].Polym.Bull.,2016,73:3183-3208.
[14] Shabir F,Erum A,Tulain U R,et al.Preparation and characterization of pH sensitive crosslinked linseed polysaccharides-co-acrylic acid/methacrylic acid hydrogels for controlled delivery of ketoprofen [J].Des.Monomers Polym.,2017,20:485-495.
[15] Ghorbanloo M,Heidary A.pH sensitive hydrogel based acrylic acid for controlled drug release [J].Phys.Chem.Res.,2017,5:185-193.
[16] Clara I,Lavanya R,Natchimuthu N.pH and temperature responsive hydrogels of poly(2-acrylamido-2-methyl -1-propanesulfonic acid-co-methacrylic acid):synthesis and swelling characteristics [J].J.Macromol.Sci.,A,2016,53:492-499.
[17] Hou P,Zhang N,Wu R,et al.Photo-cross-linked biodegradable hydrogels based on n-arm-poly(ethylene glycol),poly(ε-caprolactone) and/or methacrylic acid for controlled drug release [J].J.Biomater.Appl.,2017,32:511-523.
[18] 彭辉,罗彦凤,孙姣霞,等.新型可生物降解两性pH敏感水凝胶的制备与性能研究[J].材料导报,2010,24(14):48-51.Peng H,Luo Y F,Sun J X,et al.Synthesis and characterization of a novel biodegradable amphoteric pH-sensitive hydrogel [J].Materials Review,2010,24(14):48-51.
[19] Zhen W,Zhu Y,Wang W,et al.Synthesis and properties of amphipathic poly(D,L-lactide-co-glycolide)-polyethylene glycol-poly(D,L-lactide-co-glycolide) triblock copolymers[J].Aust.J.Chem.,2015,68:1593-1598.