Preparation And Properties Of Chitosan-based In Situ Gels

The biocompatibility and biodegradability of these materials used as injectables for drug delivery are crucial important in the field of in situ gels.For the natural macromolecular materials,physical crosslinking is the command method to prepare in situ gels,but the low strength is easily subjected to external force,irreversible deformation leads to the instability of drug release.Chitosan is a natural macromolecule with good biocompatibility and biodegradability that can be implanted into human body but is insoluble in water.Therefore,various water-soluble chitosan derivatives have been developed and gradually applied to in situ gels.Thioglycated chitosan has good bioadhesion because these thiolated macromolecules could interact with the cysteine enrichment subdomain of mucosal glycoproteins by the disulfide substitution reaction.In addition,mercapto groups react with alkynyl groups to form covalent bonds.In order to improve the biocompatibility and stability of chitosan-based in situ gels,the CS-SH and Alkynyl-PEG monomer were prepared and characterized by FT-IR and 1H NMR.A series of characterizations were conducted for the poly(CS-SH-co-Alkynyl-PEG)/Collagen hydrogels.The gelation process was characterized by rheological test and the gel structure was observed by SEM.The proliferation of L929 cells on the surface of the material indicates that the gel possessed excellent biocompatibility.Coagulation test and erythrocyte platelet adhesion test showed that these poly(CS-SH-co-Alkynyl-PEG)/Collagen hydrogels exhibited good coagulation performance and was expected to be a bioadhesive for wound repair.Subsequently,in order to improve the mechanical properties of chitosan-based in-situ gels,the prepared Alkynyl-?-CD monomer and CS-SH solution were mixed in different ratio to obtain high crosslink density and excellent degradability of poly(CS-SH-co-Alkynyl-?-CD)in situ gel.The chemical structure of Alkynyl-?-CD was confirmed by FT-IR and 1H-NMR.The chemical structures of CS-SH and Alkynyl-?-CD were unambiguously characterized by FT-IR,1H-NMR and the content of mercapto groups was quantitatively determined.The gelation process was characterized by a rheological test,DTSEM showed the pore size,the gel modulus was close to human soft tissue and the hydrogel showed good recovery after circulating compression.Subsequently,the inclusion complex was prepared by grinding with Alkynyl-?-CD and BH,and the macroscopic morphology was observed by SEM,characterization of XRD and DSC further illustrates the formation of complexes.Finally,the release test of BH in vitro in PBS buffer was conducted by using the formed in situ gels as carriers,which showed sustained release effect remarkably.Moreover,the in situ hydrogel made by chitosan and ?-CD exhibited excellent degradation performance.As stated above,the in-situ mutual-crosslinking poly(CS-SH-co-Alkynyl-?-CD)hydrogels were promising to be used as an efficient medical preparation with minimally invasive surgery applied on the treatment of solid tumors.