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Chapter 4
Chitosan-Based Drug Delivery Systems

Excerpt

Crosslinking of biodegradable polymers is potentially important to control swelling and degradation rates. The earliest work in chitosan nanostructures predominantly involved chemical cross-linking reactions to the polymer chain. Watzke et al. formed chitosan-silica nanocomposites by reacting tetramethoxysilane to the hydroxyl groups on the chitosan monomer [48]. However, attempts were not made to associate active agents to the polymer network. Ohya et al. was the first to present data involving chitosan nanospheres for the drug 5-fluorouracil (5- FU) delivery applications, using a water-in-oil emulsion method followed by glutaraldehyde cross-linking of the chitosan amino groups [49]. Yao et al. have prepared an inverse emulsion of 5-FU, or its derivative solution of hydrochloric acid, of chitosan in toluene containing surfactant (span 80). Chitosan was cross-linked with Schiff's salt formation by adding glutaraldehyde into toluene solution [50]. At the same time, the amino derivatives of 5-FU were immobilized, obviously resulting in an increase in the amount of drug within the microspheres. The microspheres were coated with anionic polysaccharides (e.g. carboxymethyl chitin, etc.) through a polyion complex formation reaction. In the case of lipid coated microsphere, the microspheres along with dipalmitoyl phosphalidyl choline (DPPC) were dispersed in chloroform. After evaporation of the solvent, microspheres were obtained coated with a DPPC lipid multilayer, which exhibited a transition temperature of a liquid crystal phase at 41.4°C. A comparative study on the release of 5-FU and its derivatives from polysaccharide coated microspheres was carried out in physiological saline at 37°C. Data indicated that the 5-FU release rate decreased in the order: free-5-FU>carboxymethyl type 5-FU>ester type 5-FU. The results revealed that the coating layers on the microspheres were effective barriers to 5-FU release. The lipid multilayer with a homogeneous composition generally shows a transition of gel-liquid crystal. When the temperature was raised to 42°C, which is higher than the phase transition of 41.4°C, the release amount of 5-FU increased. The amount of drug delivered decreased at 37°C, which is lower than the transition temperature. Due to the improved recognition function of polysaccharide chains for animal cell membranes, it is reasonable to develop targeting delivery systems from polysaccharide coated microspheres.

  • 4.1 Chitosan microspheres
  • 4.2 Chemically modified chitosan
  • 4.3 Graft Copolymerized chitosan
  • 4.4 Chitosan-based stimuli-responsive hydrogels
  • 4.5 Chitosan-ligand conjugates for active target drug delivery

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