Nasal Administration Of Recombinant Hirudin Liposomes

The recombinant hirudin-2 (rHV2) as a model drug of protein andpeptides was studied in the thesis, and nasal rHV2 liposome deliverysystem was investigated in present study. The rHV2 liposome was prepared,and then the physical-chemical properties and the primary stabilitiesof it were evaluated. Pharmacodynamic and pharmacokinetic studies onthe formulation were also carried out in rats. In the end, the toxicityof the preparation was studied in this work.Part one: literatures and summarizations Documents summarize the present research situation in the proteinand peptides,the liposomes and nasal delivery system, especially nasalliposome delivery system.Part two: Experiment studies in rHV2 liposome1. The rHV2 liposome was prepared by the modified reverse phase evapo-ration method. By the way of one-way ANOVA and orthogonal test , withthe target of encapsulation efficiency, the impact factor were reviewedto get the best prescription. Finally, the validating test showed thatthe technics of rHV2 liposome are simple and stability.2. Study on the physical-chemical properties and stability of the rHV2liposome. The research of the form, size distribution of rHV2 liposomedescribed briefly properties of the formulation, and ensured qualityand stability of it. At the same time, physical and chemical stabilitiesof rHV2 liposome were primarily studied. 3. Pharmacokinetic study on the formulation was carried out in rats.Compared to subcutaneous administration of rHV2 solution, the relativebioavailabilities (Fr) of rHV2 solution nasal administration and rHV2liposome nasal administration were determined and the pharmacokineticparameters were calculated by the software 3P87. The results showed thatthe Fr were 2.44% and 19.55% respectively, and obvious sustain-releaseattribute of rHV2 liposome and rHV2 liposome improved greatly the Fr.4. Pharmacodynamic study on the formulation was primarily investigatedin rats. With the target of APTT, the anticoagulation of rHV2 liposomeafter nasal administration was demonstrated.5. The toxicity of the nasal rHV2 liposome preparation was evaluatedin irritation and pathology. The results showed that the preparationhardly has irritation and ciliotoxicity. The mucosa morphology wouldrecover after the halt of administration.Part three: Analysis and discussion of experiments The results of the experiments are summed up, analyzed anddiscussed.