Preparation And Property Of Adamantane-and Cyclodextrin-modified Chitosan Hydrogels

Hydrogels are widely used in wound dressing,drug delivery and tissue engineering.And chitosan is an attractive material used in hydrogel preparation for its supreme biological functions.However,the bad water solubility of chitosan resulted from a large amount of interchain hydrogen bonds and compact aggregate structure limits its broader application in the field of medical care.In this thesis,chitosan was respectively chemically modified by adamantane and ?-cyclodextrin to hinder the formation of inter-chain hydrogen bonds and improve its water solubility.The chemically-modified chitosan was also cross-linked by genipin,which is of low toxicity.Firstly,adamantane was coupled to chitosan by amidation reaction between 1-adamantaneacetic acid and chitosan.And adamantane modified chitosan(AD-CS)with low substitution degree(2%)was obtained.Physically cross-linked chitosan hydrogel was prepared by directly adding a certain amount water to AD-CS.After 3 times of freezing-and-thawing process,the storage modulus at low frequency of AD-CS hydrogel raised from 50 Pa to 330 Pa.However,the adhesion strength to gelatin coating slightly declined from 29 kPa to 24 kPa.The hydrogel subjected to freezing-and-thawing process once was still of good self-healing property and this hydrogel showed a near-immediate recovery after being destroyed under high strain.But its injectability was significantly decreased after freezing-and-thawing process.Swelling tests showed that the hydrogel was not stable in weak acidic condition and it would totally dissolve after a long-term immersion.Secondly,chemically cross-linked hydrogels(AD-CS/GNP)were prepared by crosslinking AD-CS hydrogel with genipin to improve hydrogel's mechanical strength and stability.With the concentration of genipin increasing from 0.03 wt% to 0.09 wt%,the storage modulus of AD-CS hydrogels raised from 2000 Pa to 5000 Pa.Meanwhile,the start time of the modulus rapid growth was obviously shortened.Compared with CS/GNP hydrogels that prepared by dissolving chitosan in dilute acid,the mechanical strength of AD-CS/GNP hydrogels was 3~8 folds of CS/GNP hydrogels.And AD-CS/GNP hydrogels' start time of modulus rapid growth was shorter than CS/GNP hydrogels' gelation time.The swelling ratio of AD-CS/GNP hydrogel with genipin concentration of 0.09 wt% in water was approximately 4 g/g,higher than its swelling ratio in phosphate buffered saline(PBS).And the cumulative releasing amount of tetracycline hydrochloride in water was also higher than that in PBS.Finally,chitosan was chemically modified by ?-cyclodextrin and water-soluble chitosan(CD-CS)was obtained.Chemically cross-linked hydrogels were simply prepared by crosslinking CD-CS with genipin.The influence of the substitution degree of CD-CS on properties of the hydrogels was studied.With the substitution degree of CD-CS increasing from 5.2% to 9.8%,the gelation time increased from 170 min to 240 min and the mechanical strength decreased from 3000 Pa to 500 Pa.The swelling ratio of CD-CS/GNP hydrogels also obviously decreased with the increasing of substitution degree.Drug releasing property of AD-CS/GNP hydrogels was studied with hydrophobic 5-fluorouracil used as model drug.At the beginning of drug releasing,the releasing rate of 5-fluorouracil increased with the increasement of substitution degree.While the slow releasing process of high substitution degree hydrogel was more obvious and the total releasing amount of 5-fluorouracil was higher than hydrogel with lower substitution degree.