Carboxymethyl Chitosan Based Hydrogels:Synthesis,Characterization And As Carriers For Sustained Release Of Cisplatin

Cisplatin is a common cell-cycle nonspecific antineoplastic agent in clinical.It can be used for the treatment of solid cancer such as ovarian cancer,testicular cancer,gastrointestinal cancer,head and neck cancer,bladder cancer,small cell lung cancer,esophageal cancer and cervical cancer.Cisplatin lost its activity soon after clinical injection as cisplatin combine with protein.Moreover,cisplatin has a very long half-life.Unfortunately,because of the severe side-effects like nephrotoxicity,neurotoxicity,bone marrow suppression,etc.,it is limited in clinical.In this work,we develop a new cisplatin delivery system which is safe and nontoxic,can be used in local lesions,and prolong the release of cisplatin.In the present materials,hydrogels which have good biocompatibility,biodegradability and biological activity were widely favored by researchers.Carboxymethyl chitosan is a natural polymer with good biocompatibility,adhesion and a variety of biological activity.With the properties of non-toxic,non-immunogenic,may be biodegradable by a variety of enzymes,degradations of non-toxic products and can be fully absorbed by the organism,its based hydrogel is always designed for drug delievery system for controlled release.N-isopropylacrylamide is a temperature sensitive material and there is hydrophilic amide group and hydrophobic isopropyl on its poly(N-isopropylacrylamide)based hydrogel.As a result,N-isopropylacrylamide is often introduced to different biomedical hydrogels as a temperature-sensitive portion in drug release.In this work,poly(N-isopropylacrylamide)/carboxymethyl chitosan hydrogels(pNIPAAm/CMCS)were prepared by using NIPAAm and CMCS as monomer,BIS as crosslinker,APS as initiator and TEMED as accelerant by chemical cross-linking.Scanning electronic microscopy images showed that the hydrogels exhibited a cross-linked structure with the average pore size from 111 to 206 ?m.It can be seen that the hydrogels has good swelling abilities as the highest equilibrium swelling ratio at 100 min was 1470%.Part of CDDP molecules were conjugated with carboxyl group of CMCS moieties in the pNIPAAm/CMCS hydrogels,the other CDDP molecules were encapsulated by penetration pathway into the network of the hydrogels.The cumulative release percentage of CDDP from pNIPAAm/CMCS hydrogels was studied.In vitro release experiment demonstrated that the release of CDDP was controllable and sustained over a long period.Moreover,Fickian behaviors may suggest that the CDDP release process was controlled by drug diffusion only.By testing the released cisplatin solution inhibition rates of A549 cells,it could be seen that the released cisplatin showed good inhibition.The released CDDP retained its anticancer activity on A549 cells,for MTT assays showed that the A549 human lung cancer cells were significantly inhibited.The MTT assays also implied that the hydrogels had good biocompatibility as the NIH3T3 cell viability was higher than 84%for all kinds of hydrogel.The hydrogels are promising carriers for sustained release of cisplatin.