Preliminary Study On Inner Ear Targeted Drug Delivery By Postauricular Hypodermic Injection

Blood labyrinth barrier is a focus in auristics research in recent years. The tissue of inner ear is separated from blood by BLB, which could maintain the stability of composition of fluid in inner ear. Not simply, BLB keeps IE away from invasion and destruction by various toxic substances,microorganisms,autoimmune disease as far as possible. Curatives consisting of large molecules could not get into inner ear easily because of the baffle of BLB, besides, some curatives consisting of small molecules could not overcome the obstacle either for they possess incorrect electric charge. So theoretically local application is safer and more effective than systemic administration because the former could get round BLB. However, due to the special structure and anatomical position of IE, there are respective shortages in all the local application methods. It is urgent to find a new administration route in order to make medicine get into IE more safely,effectively and persistently.Objective:To verify the feasibility of inner ear targeted drug delivery by postauricular hypodermic injection. To find out if there is a direct lymph-channel between the inner ear and hypodermia of postauricular mastoidea, through which the curatives could bypass BLB and get into endolymph or perilymph. To analyze and expound its characteristics if there is indeed such a channel.Methods:(1) The guinea pigs were randomly allocated into two groups: EB-vein shot group, EB-postauricular hypodermic injection group. EB-Saline solution was injected through vein and postauricular hypodermia respectively. The level of blue-stain in skin and mucous membrane were observed. The EB in endolymph and endolymph was absorbed by using dimethylformamide( DMF ). Amount of EB in DMF was detected by spectrofluorophotometer.(2) Serum was isolated from guinea pig's blood. The fluorescence of EB-serum solution was observed by the method of smear. The guinea pigs were randomly allocated into two groups: EB-vein shot group, EB-postauricular hypodermic injection group. EB-serum solution was injected through vein and postauricular hypodermia respectively. Perilymph was collected from cochlea and observed carefully with fluorescent microscope if there were EB-albumin fluorescent particles in it. Distribution of EB-albumin fluorescent particles in frozen cochlea section was observed.Results:(1) The level of blue-stain of skin and mucous membrane in EB-vein shot group was higher than which in EB-postauricular hypodermic injection group. The amount of EB in inner ear was not detected in the two groups reliably.(2) There were fluorescent particles emitting bright red flourescence in EB-serum solution smear. However, there were not fluorescent particles in EB-saline solution smear. EB-serum fluorescent particles were not detected in perilymph,membrana vestibularis,basal membrane,Corti's organ or other parts in the two groups.Conclusions:The amount of EB in perilymph was not detected in the two groups. Abundant EB molecules could gather into fluorescent particles complexed with albumin. And the fluorescence intensity will enhance remarkably accordingly, which could be easily observed with fluorescence microscope. EB-serum fluorescent particles were not detected in inner ears of two groups. To sum up: there is no evidence to prove that there is a direct lymph-channel between the inner ear and hypodermia of postauricular mastoidea .