Preparation And Characterization Of Chitosan Hydrogel For Localized Drug Delivery System

Chitosan is widely used for localized drug delivery system because of itsexcellent biodegradability and biocompatibility, however chitosan could not directlysoluble in water. Chemical modifcation is important and necessary to improve itssolubility. During the modification, photosensitive functional groups could begrafted on the chitosan, which can be photo-crossslinked to create hydrogels.Photo-crosslinked hydrogels has many advantages, such as: gentle reactionconditions, short gelation time, injectable hydrogels with different shapes and sizes.However, the current approaches to synthesis water-soluble and photo-crosslinkablechitosan have some challenges, such as complex steps, long term of UV irradiation.In the paper, one step reaction was used to prepare the water-soluble andphoto-crosslinkable chitosan mathacrylamide(CM).~1H NMR, FTIR, XRD, ESEMwere used to characterize the molecular structure, degree of substitution(DS). Theeffect of DS on the solubility, water content, swelling ratio and degradation ratewere investigated, the drug release behavior and mechanism of and rifampin(RFP),one of first line clinical drug, in vitro were studied.With increasing reaction temperature and C=C/-NH2, the solubility and DSincreased, the degree of crystalline decreased. When DS increasing from17.3%to52.1%, the solubility significantly increase from1.6mg/ml to10mg/ml, it is a5.25times. CM was photo-crosslinked to form CM Hydrogel(CMH) by UV irradiation.The crosslinking time increased from30s to80s with the varying DS from52.1%to17.3%. The degradation rate and equilibrium swelling ratio of CMH scaffoldincreased with the decreasing DS. With the varying DS from52.1%to17.3%, theequilibrium swelling ratio increased from9.1times to13.6times, the degradationrate increased from50.6%to68.2%by3weeks.CMH loaded with RFP released over90%after6hour, and the drug releaseperformance depended on the combination between RFP and CMH. With theincreasing of RFP concentration and the addition of hydroxyapatite, the binding freeenergy decreased, leading to a slower drug released. RFP released slower fromCMH scaffold than from CMH. CM hydrogel had many advantages, such as: in situgelation, in situ trapped drug in gentle condition and homogeneously with a100%uploading efficiency, RPF/CMH would have potential applications in localized drugdelivery system to treat bone defect due to tuberculosis.Concentric Layered Chitosan Hydrogel scaffold loaded with RFP had the drugreleasing properties of burst release and short release time. The addition of chitosansealing layer or CMH sealing layer could overcome the above shortcomings with a decreased drug release rate of51.2%and46.9%after1h and30.0%and63.3%after50h, respectively. The release was controlled by the Fickian diffusion. The additionof CMH sealing layer out chitosan/apatite played a certain sealing effect with slowrelease and long-term release.