Experimental Study On The Prevension And Cure Of Cerebral Vasospasm By Intracisternal Infusion Of Polymer Microspheres Of Nicardipine

Part One: The preparation of NC-PLGA microspheres and experimentalstudy on the pharmacokinetics in vivo and vitro with microspheresObjective:Preparation of biodegradable NC-PLGA microspheres.Investigate the technology of preparation and release in vivo and vitro with microspheres.Methods: NC-PLGA microspheres were made by oil/water solvent evaporation method. Study the release speed in artifical cerebrospinal fluid by ultraviolet spectrophotometry, NC-PLGA microspheres were injected through the cisterna magna of rabbits to investigate releasing in vivo by HPLC.Results:The average particle size of the NC-PLGA microspheres was 31.3±3.2μm, the drug-loading ratio was 13.7%, and the entrapment efficiency was 89.2%.Studies on the release in vitro showed that nearly on the first tow days initial burst release about 30% could be seen, drug could release slowly in 20 days.CSF concentration time profiles have shown that nicardipine released from the microspheres slowly and steadily after the initial burst effect, and it's Carbinoxamine Compound Drops density retains about 7.6 X 10^-8mol/L everyday. Conclusions: NC-PLGA microspheres were made by oil/water solvent evaporation method. Studies on it showed that NC-PLGA microspheres is a local slow release drug in cranial. Part Two: Experimental study on the therapy of cerebral vasospasm by intracisternal infusion of NC-PLGA microspheresObjective:To study the therapeutic effects of intracisternal infusion of NC-PLGA microspheres solution on rabbits cerebral vasospasm(CVS) models. Methods:The primary SAH rabbit models were produced by injecting -blood two times through the cisterna magna.The CVS rabbit models were treated by intracisternal infusing of NC-PLGA microspheres and Nicardipine solution.The basal arteriospasm was observed with Transcranial Doppler.The diameter of basilar arteries were measured by cerebral angiography to evaluate the severity of CVS .The pathological changes of basilar artery walls were examined. Results: Intracisternal infusion both NC-PLGA microspheres and Nicardipine can reduce the severity of CVS.And they can reduce the obvious morphological changes in the artierial wall of BA also.Compared with intracisternal infusion Nicardipine, using 25% dose of intracisternal infusion NC-PLGA microspheres canget the same effective.Conclusions: The intracisternal infusion NC-PLGA microspheres can reverse the severity of CVS and reverse the pathologic changement in the arterial wall.The therapy course is simple and reducing complication.The technique with polymer should guide the therapy of cerebral vascular disease to some extent.