Studies On Chitosan Nanoparticles Modified With Glycyrrhetinic Acid By Targeting Drug Delivery

Multifunctional drug delivery system of organelle targeting is the research focusof the preparation. how to achieve the grading and successive function ofmulti-functional drug delivery system to avoid the interaction between variousfunctionsof the drug delivery system is one of the difficulties.The aim of this thesis isto design, synthesis and characterization of pH-sensitive chitosan derivatives of thelysosomal environment, as well as lysosomal escape of chitosan derivatives, anddelivery of the two materials to build multi-functional drug system. Choosing thebrucine as a model drug, we expected that the new nanoparticle can increase theconcentration in mitochondria of liver cells and reduce its toxicity.In the first part of this thesis, the novel polymer material was synthesized andcharacterized with1H-NMR and FT IR, and they all showed the peaks ofglycyrrhetinic acid. And we also investigated the pH-sensitive and solubility of thesenovel polymers,it still showed the different properties.Optimal formulation of Brucine nanoparticle MNP modified with NGPC andNQC were determined using composite design. Response variables selected in theresearch were entrapment efficiency (%), particle size (nm) and drug loading. Thedata were transformed into desirabilities. The observed values agreed well with modelpredicted values. Central composite design-response surface methodology wassuccessfully used to optimize the formulation of MNP. Then compared with NGPCand NQC in vitro physical and chemical, the accumulated release and storage stabilitywere better than them. The MNP was found that it was round or oval structure andsurrounded by a thin layer of material may be due to the long chain of the polymerusing transmision electron microsocopy.To evaluate the pharmacokinetics and the parameters of these preparations, westudy the pharmacokinetics, tissue distribution and animal imaging in rat in the fourthof this thesis, respectively. The result showed that the MNP was able to improve the liver targeting of brucine compare with NQC, the AUC of MNP was much higher thanthat of NQC.The concentration of drugs was significantly increased in the liver, theresidence time was prolonged and the concentration of drugs in the brain wasdiscreased greatly.