Polyelectrolyte Coating Hollow Hydroxyapatite Preparation And Controllable Drug Delivery Property

Hydroxylapatite (HAP), which is major inorganic component of human teethand bone, has been widely used in biomedical area because of its good biologicalactivity, biocompatibility. The CHI/SA-HAP hollow hybrid microparticles, whichexhibited excellent pH-dependent and sustained drug release properties, wereachieved by combining HAP hollow microparticles and chitosan/sodium alginate(CHI/SA) multilayers through the layer-by-layer self-assembly technique (LbL). Thedrug delivery carrier not only enriches the application of HAP as drug delivery carrierbut also provides a new way to obtain the potential drug carrier with high drugloading efficiency and good drug release properties. This thesis includes two majorsections：Firstly, the paper explored the synthesis conditions of HAP microparticles usedas an excellent inorganic template for the preparation of CHI/SA-HAP hollow hybridmicroparticles. Calcium carbonate microparticles were prepared by fast precipitationmethod used PSS, EG as regulators, and converted to HAP by hydrothermal method.The results were characterized by such techniques as SEM, EDX and FT-IRspectrometer, which were used to determine the optimal conditions for the synthesisof HAP microparticles. Characterization and experimental results showed that, withPSS as modifier, calcium carbonate microparticles could be prepared, andtransformed into spherical hydroxyapatite in0.93M disodium hydrogen phosphatesolution.Secondly, HAP microparticles were fabricated in disodium hydrogen phosphatesolutions by hydrothermal method using PSS–doped vaterite CaCO3microparticles astemplate. The CHI/SA-HAP hollow hybrid microparticles were achieved bycombining HAP hollow microparticles and chitosan/sodium alginate CHI/SAmultilayers via the LbL self-assembly technique. The prepared CHI/SA-HAP hollowhybrid microparticles with a hollow HAP core and polymer multilayer shell werecharacterized by such techniques as SEM, TEM and FT-IR spectrometer. The drugloading and release investigation indicated that the drug loading efficiency of CHI/SA-HAP hollow hybrid microparticles was90.0%, which was much higher thanthat of HAP microparticles (39.6%); it is clear that the inner hollow space plays animportant role in enhancing the drug loading efficiency of hybrids. Additionally, theCHI/SA-HAP hollow hybrid microparticles exhibited outstanding pH-dependent andsustained drug release properties. Compared to the HAP microparticles, theintroduction of polymer multilayer coating could avoid the direct contact betweenhollow HAP microparticles and the outside medium, which would reduce the drugrelease and assuage the initial burst release of DOX. The pH-sensitive drug deliverycould be attributed to the different electrostatic interaction in the CHI/SA multilayersat different pH values and the dissolution of hollow HAP core at acid condition. Thekinetics of DOX release from the CHI/SA-HAP hollow hybrid microparticles hadbeen analyzed by plotting the cumulative release data versus time by fitting them tothe Ritger-Peppas equation. The result indicates that the introduction of CHI/SAmultilayer and the change of pH have evidently changed the release kinetics of DOX.