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基于液体预聚物原位形成可降解的聚(乙二醇)-聚(己内酯)-聚(甲基丙烯酸2-二甲基氨基乙酯)两亲性互穿网络凝胶,呈现极性驱动凝胶化和生物粘附性

Liquid Prepolymer-Based in Situ Formation of Degradable Poly(ethylene glycol)--Poly(caprolactone)--Poly(2-dimethylaminoethyl)methacrylate Amphiphilic Conetwork Gels Showing Polarity Driven Gelation and Bioadhesion.

作者信息

Nutan Bhingaradiya, Chandel Arvind K Singh, Jewrajka Suresh K

机构信息

Membrane Science and Separation Technology Division, Academy of Scientific and Innovative Research, CSIR-Central Salt and Marine Chemicals Research Institute G. B. Marg, Bhavnagar, Gujarat 364002, India.

出版信息

ACS Appl Bio Mater. 2018 Nov 19;1(5):1606-1619. doi: 10.1021/acsabm.8b00461. Epub 2018 Oct 24.

Abstract

Amphiphilic conetwork (APCN) gels suffer from lack of direct injectability due to use of organic solvent, prolonged crosslinking/polymerization process and immiscibility between hydrophilic and hydrophobic prepolymers. On the basis of prepolymers compatibility and polarity, we report the use of an advanced prepolymer liquid system for in situ construction of APCN gels. Solid elastic poly(ethylene glycol)--poly(ε-caprolactone)--poly(2-dimethylaminoethyl)methacrylate (PEG--PCL--PDMA) APCN gels were formed upon addition of an appropriate amount of PDMA diluted in nonreactive sacrificial liquid PEG into a compatible blend of activated halide terminated PEG and PCL liquids. Compatibility among the prepolymers allowed favorable gelation. The polarity of the prepolymer liquid greatly influenced the gelation time. PEG--PCL--PDMA APCN gels were cytocompatible/biodegradable and showed storage modulus in the range of 50-200 kPa and bioadhesive strength of 40-90 kPa. The fluorescence experiments showed that the hydrophobic probe, pyrene was distributed in both hydrophilic and hydrophobic phases of the APCN gels. These APCNs exhibited sustained release of hydrophobic and hydrophilic drugs. Effects of polarity, composition, and molecular weight of the liquid prepolymers on the gelation time, rheological property, and swelling behavior of the APCN gels have been investigated in details.

摘要

两亲性互穿网络(APCN)凝胶由于使用有机溶剂、交联/聚合过程延长以及亲水性和疏水性预聚物之间的不混溶性而缺乏直接可注射性。基于预聚物的相容性和极性,我们报道了一种用于原位构建APCN凝胶的先进预聚物液体体系。当将适量稀释在非反应性牺牲液体聚乙二醇(PEG)中的聚(2-二甲基氨基乙基)甲基丙烯酸酯(PDMA)添加到活化卤化物封端的PEG和聚己内酯(PCL)液体的相容共混物中时,形成了固体弹性聚(乙二醇)-聚(ε-己内酯)-聚(2-二甲基氨基乙基)甲基丙烯酸酯(PEG-PCL-PDMA)APCN凝胶。预聚物之间的相容性有利于凝胶化。预聚物液体的极性极大地影响了凝胶化时间。PEG-PCL-PDMA APCN凝胶具有细胞相容性/可生物降解性,其储能模量在50-200 kPa范围内,生物粘附强度在40-90 kPa范围内。荧光实验表明,疏水性探针芘分布在APCN凝胶的亲水相和疏水相中。这些APCNs表现出疏水性和亲水性药物的持续释放。已详细研究了液体预聚物的极性、组成和分子量对APCN凝胶的凝胶化时间、流变性能和溶胀行为的影响。

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