Preparation And Characterization Of Hyaluronic Acid Hydrogel For Cancer Treatment

As a main way to treat cancer,targeted therapy needs carriers with specific functions.The carriers should have the functions both of targeting and controlled releasing.Hydrogels with three-dimensional porous structure have good biocompatibility and controllable microstructure,which are important to used in tissue engineering,drug delivery,drug delivery and other fields.Hyaluronic acid（HA）is a kind of natural linear polysaccharide with biodegradability and biocompatibility.Due to its special spatial structure,HA can achieve targeted recognition by hydrogen bond shearing with the overexpressed CD44 protein on the surface of cancer cells and can be used to treat cancer.In this paper,the preparation technique and behavior of controlled drug release of HA/Fe₃O₄/Ag⁺,HA/Fe₃O₄/MSNs and CS/HA/Fe₃O₄ hydrogels are studied.The main works and conclusions are as follows:（1）Magnetic Fe₃O₄ nanoparticles are prepared and modified to be used as cross-linking sites of HA gels.HA-SH is synthesized and crosslinking polymerized with surface modified magnetic nanoparticles by Michael addition reaction.The effects of different degradation time and molecular weight of HA are discussed.The effect of monomer contents on the properties of the HA/Fe₃O₄/Ag⁺hydrogels are also discussed.The results show that the storage modulus of the gels can achieve 221 Pa when the HA degradation time is 7 days,the HA molecular weight is 10000,the mass ratio of Ag⁺,HA-SH and Fe₃O₄ magnetic nanoparticles is 1:10:1.The HA/Fe₃O₄/Ag⁺gels can be used in injectable hydrogel materials due to the property of shear thinning.（2）Mesoporous silica nanoparticles（MSNs）are prepared to realize the controlled drug release property of HA hydrogels as crosslinking sites.The effect of MSNs concentration on the HA/Fe₃O₄/MSNs hydrogels properties is explored.The results show that the specific surface area,pore volume and pore size of the MSNs decreased.The pore size is 33.4nm,the high specific surface area is 342m²/g and the large pore volume is 0.65 cm3/g.When the mass ratio of MSNs,HA-SH and Fe₃O₄ magnetic nanoparticles is 1:10:1,the mechanical property of HA/Fe₃O₄/MSNs gels are the best.With increasing the content of MSNs,the gel network tends to be dense.Therefore,the content of drug remaining in gel increases,and the drug release tends to linear.（3）Chitosan（CS）are add to the gel systems to reduce the biological toxicity and nanoparticles content,improve the drug controlled release capacity and mechanical properties.The effects of different monomer contents on the properties of the CS/HA/Fe₃O₄ hydrogels are explored.The swelling and drug release properties of the gels are also studied.The results show that the tensile strength and the elongation of Fe₃O₄/HA/CS hydrogels are 254kPa and 490%when the content of CS and HA is 3wt%and 2 wt%.At the same time,the swelling property of the hydrogel is also the best.