The Research Of The Effect Of Local Delivery Of Biodegradable Polymeric Glucocorticosteroid On Traumatic Brain Edema

Traumatic brain edema (TBE) is the most capital reason for the death of traumatic brain injury. There is no way for radical treatment right now. Earlier and recent studies showed that there is significant effection for the reduction of traumatic brain edema of severe head injury and decreasing of the mortality and morbidity with the use of high steroid-dose treatment. But it is clear that there is the risk of inducing severe systematic side-effect with a high steroid-dose treatment. So it is restricted greatly to use it in clinic. Local administration of high dose giucocorticosteroid can provide high concentration on the site of delivery by using a low steroid-dose and avoid the side-effect caused by bodily using highdose glucocorticosteroid. The objective of this study was to minimize the side effects by local delivery of dexamethasone sodium phosphate(DSP), and to find a better therapeutic way for TBE. We used Polylactide-co-glycolide (PLGA) as the polymer to deliver dexamethasone (DXM) in the brain of animal and test the biological effects of the complex in virto and in vivo.In part one, microspheres containing 6.1% DSP were synthesized by the solvent evaporation method. The average particle size of the microspheres was 29.93 m 4.10 m. The release kinetics of DSP from the DSP-PLGA microspheres were studied. The in-vitro release time was 48h in pH 7.4 37 PBS. However it can be extended to 1 week by compressing the complex into tablets. There is an initial peak effect in the release course. For the in-vivo studies, the release kinetic of DXM from the DSP-PLGA tablets that be implanted into the normal rat brains shows that the higher the DXM level in the brain tissue closer to the tablets. The average concentration of DXM in the implanted brain tissue is 38.49 g/g, 11.52 g/g, 6.31 g/g and 0.51 g/grespectively, at 1 hour, 1 day, 3 day and 1 week after the implantation. The DXM average levels in the ipsilateral hemispheres is from 20 g /g to 4 g /g during the first 3 days.In part two, to observe the effects of the DSP-PLGA tablets treatment on the rat TBE model, we used the doubled-blind test. The rats were divided into four groups: the intracranial DSP-PLGA implantation, the intraperitoneal DSP-PLGA implantation, the vein DSP injection and the control. The result showed that water content and Evans blue effusion in the ipsilateral hemispheres were significantly reduced in the intracranial DSP-PLGA implantation when compared to other groups(P<0.01). The pathologiclal observation showed that the intracranial DSP-PLGA implantation can protect the cell and cytoarchitecture form damage.The studies show that local administration of biodegradable DXM is safe and effective to treat TBE. The DSP-PLGA is a kind of ideal sustained-releasing steroid and deserved to be investigatedand use broadly.