The Preration Of Hydrogels Based On Recation Of N-maleoyl Alanine

Hydrogel is a kind of excellent biological materials and it is biocompatible andbiodegradable. Recently, hydrogel has been used as drug-controlled release materials.Click chemistry is a fast and efficient method for preparing of various kinds ofcompounds. So click chemistry has been applied widely in lots of fields, such asmacromolecule chemistry, biological coupling technology, biomedicine and so on.In this paper, maleic anhydride and L–alanine were used as the raw materials, andN-maleoyl alanine (AMI) was synthesed through two steps. Then hydroxyethyl-beta-cyclodextrin (HCD) and polyethylene glycol (PEG) were modified by AMI, soHCD-AMI and PEG-AMI were prepared respectively. On this basis, the hydrogelwas prepared through click reaction between HCD-AMI, PEG-AMI and thecopolymer containing azide groups and the copolymer containing furan groups,respectively. The experimental method and results are as follows:1. The hydrogels were prepared through1,3-dipolar cycloaddition clickreaction between HCD–AMI and copolymer containing azide groups. Firstly,binary copolymer (PMADA-n) was prepared through free radical polymerizationreaction with acrylic acid (MA) and N, N-dimethyl acrylamide (DA). AIBN wasused as the initiator in this reaction. And monomer mole ratio (MA/DA) was1:5,1:10,1:15, and1:20respectively. Then the copolymer containing azide group(PMADA-AZ-n) was prepared through coupling reaction of2-Azidoethanol (AZ)and binary copolymer carboxyl with dicyclohexylcarbodiimide (DCC) asdehydrating agent. With water as the solvent, the chemical crosslinked hydrogel wasprepared by1,3-dipolar cycloaddition reaction between HCD-AMI and PMADA-AZ–n. The characteristics of the hydrogels and the results are as follows：Thegelation time was shorter and the yield of the hydrogel was higher when the contentof azide group in the copolymer was increasing；the swelling degrees of the differentmonomer ratio hydrogel were different and responsive to temperature. Whentemperature was lower than47℃, the hydrogel constantly absorbed water and swelled, when the temperature was higher than47℃, the swelling degree waslower as temperature increased; the release rate of the hydrogel for daidzein was fastin the beginning, then gradually was balanced；The SEM shows that pore size of thehydrogel was larger when the content of azide group in the copolymer was less.2. The hydrogels were prepared through Diels-Alder click reaction betweenPEG-AMI and the copolymer containing furan ring. The method of preparing thecopolymer containing furan ring is as follows: firstly, four kinds of binary copolymer(PNIPAMA-n) methyl was prepared through radical polymerization reaction withN-Isopropyl acrylamide (NIPA) and maleic anhydride (MA). And the mole ratio(NIPA/MA) was10:1,15:1,20:1, and25:1, respectively. Then the PNIPMA-n wasmodified with furfuryl amine (FA) and we could get the copolymer containing dienegroups (PNIPAMA-FA-n). With water as the solvent, the chemical crosslinkedhydrogel was prepared by Diels-Alder reaction of PNIPAMA-FA-n and PEG–AMI. Then the characteristics of intermediate and hydrogels were carried out and theresults are as follows: the lowest critical solution temperature of different monomercontent of the binary copolymer increased with the increasing of the monomercontent of maleic anhydride; the lowest critical solution temperature of polymericdienes was between37.5~48.5℃; when the temperature was25℃, the swellingdegree of the hydrogel was balanced after3.5hours; the hydrogel possessestemperature sensitivity and pH sensitivity.