Chitosan And Its Derivatives As Drug Delivery Carriers And Scaffolds

Chitosan is obtained by alkaline deacetylation of chitin, which is the second most abundant natural biopolymer derived from exoskeleton of crustaceans and also from cell walls of fungi and insect. Chitosan as a cationic natural polysaccharide has excellent biological activities, such as biocompatibility, biodegradability, antibacterial, and wound-healing activities, as well as physical-chemical properties. Therefore, chitin and chitosan are currently being explored intensively for their applications in agricultural, food, pharmaceutical, cosmetics, biotechnological, and other industries due to their unique physical and chemical properties. Chitosan and its derivatives are promising candidates as biomedical materials and receiving a great deal of interesting for biomedical applications such as drug, protein, and gene carriers, tissue engineering scaffold, wound dressing and so forth. However, chitosan is normally insoluble in both water and organic solvents due to its stable rigid crystalline structure, formed by intra-and/or intermolecular hydrogen bonding, and therefore limit their application. To exploit the unique properties and to realize full potential of versatile polysaccharide, attempts are being made to derivative it. To exploit the potential application of chitosan, two chitosan derivatives----polymerizable glycidyl methacrylate functionalized chitosan (CS-GMA) and water-soluble methoxy poly(ethylene glycol)-grafted chitosan (PEG-g-CS)----were prepared by epoxy ring opening reaction and Michael Addition reaction, respectively. Chitosan and its derivatives were utilized to fabricate various materials, which have potential application in biomedical field such as hydrogels, porous scaffolds, composites and nanofibers. The main contents and conclusions are described as follows.1. The polymerizable chitosan derivatives (CS-GMA) with different degree of substitution (DS) were synthesized by covalent attachment of glycidyl methacrylate (GMA) to chitosan via epoxy ring opening reaction. FT-IR and1H-NMR spectroscopes confirmed the incorporation of vinyl group onto chitosan backbones. The incorporation of GMA changed chitosan state from semi-crystallization to amorphous demonstrated by XRD results. TGA results implied thermal stability of CS-GMA was lower than that of chitosan for its lower decomposition temperature. A series of hybrid polymer network (HPN) hydrogels based on glycidyl methacrylated chitosan and N-isopropylacrylamide were designed and prepared via photopolymerization. Hybrid hydrogel exhibited combined pH-and temperature-sensitivities and could be used as drug carriers. The drug release profiles depended on hydrogel component ratio, environment (pH and temperature) and the interaction between hydrogel and model drug molecule.2. Porous scaffolds composed of alginate (AG) and chitosan (CS) were prepared by combining the formation of polyelectrolyte complex (PEC) with freeze-drying. Uncrosslinked alginate scaffold and Ca2+crosslinked alginate scaffold were also prepared for comparison. Porosity, microstructure, mechanical strength, thermal stability and surface element of various scaffolds were investigated. PEC scaffold exhibited better mechanical strength and thermal stability, compared with Ca2+crosslinked alginate scaffold. Besides, the porosities of various scaffolds exceeded70%and therefore would be used as tissue engineering materials.3. Water-soluble chitosan oligosaccharide (CSO) and methyl methacrylate were utilized to prepare chitosan oligosaccharide/poly(methyl methacrylate)(CSO/PMMA) composites by combining freeze-drying with radial polymerization. The composites are promising candidate as partially degradable and bioactive acrylic bone cements. The compression modulus, dynamic mechanical property, thermal stability and crystalline state of composites were investigated. The CSO is water-soluble and therefore would be extracted gradually from the composites. After the CSO extracted from the composites, porous PMMA could be obtained. The microstructures of porous PMMA were observed by SEM and the results suggested that PMMA exhibited interconnected but irregular pore structure. Moreover, the compression modulus of initial composites and porous materials after immerged in PBS solution for eight weeks were investigated.4. Methoxy poly(ethylene glycol)-grafted chitosan (PEG-g-CS) derivatives were synthesized by mild Michael Addition reaction of chitosan with methoxy polyethylene glycol monoacrylate. The physical and chemical properties of the derivatives were studied by FT-IR,1H-NMR, XRD and TG. The degradability of PEG-g-CS were also investigated. Biocompatible PEG-g-CS/poly(ethylene oxide)(PEO) nanofibers were successfully prepared by electrospinning. The effect of polymer composition on the fiber formation, morphology, diameter distribution, microstructure and crystalline state were investigated. Besides, the water or solvent resistances of crosslinked or uncrosslinked electrospun membrane were studied. The results showed that the content of PEG-g-CS decreased below80%, continuous and smooth nanofibers with uniform diameter distribution could be obtained.