Preparation And Properties Of Hyaluronic Acid/N-isopropylacrylamide Composite Hydrogels

Most of the drug controlled release smart hydrogels are injectable hydrogels,but the degradation rate is too fast,the drug release cycle is short,and it is not suitable as a medium and long-term drug release carrier.So,improving the stability of drug controlled release smart hydrogels has attracted much attention.The low critical phase transition temperature（LCST）of poly（N-isopropylacrylamide）（PNIPAM）is range from 30℃to 32℃,and it is a temperature stimulus responsive polymer.There are a large number of active groups in the molecular chain of hyaluronic acid（HA）for chemical modification,which can be grafted and modified toendue it more performance.In this thesis,modified hyaluronic acid and NIPAM are compounded to prepare a temperature-sensitive composite hydrogel with high stability and potential application in controlled drug release.Using HA and methacrylic anhydride as raw materials,under low-temperature alkaline conditions,the esterification reaction is used to obtain methacryloyl hyaluronic acid（HAMA）.Using HAMA and NIPAM as precursors,APS as initiator,and radical polymerization at 70℃,temperature-responsive HAMA/NIPAM-x hydrogels with HAMA as the main chain and NIPAM as the grafted side chain were prepared.Research on the microscopic morphology,swelling,degradation,rheological properties and in vitro drug release behavior of the hydrogels.The results indicate that the HAMA/NIPAM-x hydrogels have an obvious three-dimensional network porous structure;they can quickly absorb water and swelling,and achieve swelling equilibrium about 10 hours,swelling ratio is 15-23;Research on degradation behavior in PBS solution at different temperatures（p H 7.4）,the degradation percentages of 30 days are low,and the stability is good.For example,at 25℃,30℃,32℃and 37℃the degradation of HAMA/NIPAM-1 is 16%,6%,7%and 19%,respectively.Taking bovine serum albumin（BSA）as a model drugthe average drug loading ratio is about 76%;in the PBS solution（p H 7.4）at different temperatures,the hydrogel performs well controlled drug release ability;those hydrogels have good rheological properties.SiO₂ with an average 300 nm particle size are prepared by hydrolysis of ethyl orthosilicate.By introducing organic silicon source bis-[γ-（triethoxysilyl）propyl]-tetrasulfide（BTES）.Hollow organosilicon microspheres were prepared and blended with HAMA and NIPAM to obtain HOSM/HAMA/NIPAM-x composite hydrogels through radical polymerization.The microscopic morphology,swelling,degradation,and rheology of the series of hydrogels were obtained.The performance and in vitro drug release behavior were studied.The results show that the series of hydrogels have a three-dimensional network porous structure;they can quickly absorb water and swelling,reaching a swelling equilibrium about 12 hours,swelling ratio is 16～26;they have good stability in PBS solutions（p H 7.4）at different temperatures,30 d The degradation percentage is lower,such as HOSM/HAMA/NIPAM-1.The degradation percentages at 25℃,30℃,32℃and 37℃are about 20%,17%,21%and 17%,respectively.And the weight loss rate is faster than that of HAMA/NIPAM-x hydrogels;the average drug loading ratio of the HOSM/HAMA/NIPAM-x hydrogels is about 78%,which can achieve better controlled drug release.Compared with the HAMA/NIPAM-x hydrogels series of hydrogels all show good rheological properties and shear thinning properties.In summary,the prepared hydrogels have good stability and good drug controlled release ability,and have potential application value in the field of medium and long-term drug controlled release.