Ultraschall-gesteuerte Freisetzung von an Nanopartikeln gebundenem Nimodipin und deren Anwendung zur Therapie von experimentell erzeugten Vasospasmen an der Chorioallantoismembran des embryonalen Eis

by Katja Döring née Döring
Doctoral thesis
Date of Examination:2022-12-13
Date of issue:2022-12-05
Advisor:PD Dr. Vesna Malinova
Referee:PD Dr. Vesna Malinova
Referee:Prof. Dr. Thorsten Roland Döppner
Persistent Address: http://dx.doi.org/10.53846/goediss-9606

 

 

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Abstract

English

Nimodipine prevents cerebral vasospasm and improves functional outcome after aneurysmal subarachnoid hemorrhage (aSAH). The beneficial effect is limited by low oral bioavailability of nimodipine, which resulted in an increasing use of nanocarriers with sustained intrathecal drug release in order to overcome this limitation. However, this approach facilitates only a continuous and not an on-demand nimodipine release during the peak time of vasospasm development. In this study, we aimed to assess the concept of controlled drug release from nimodipine-loaded copolymers by ultrasound application in the chicken chorioallantoic membrane (CAM) model. Nimodipine-loaded copolymers were produced with the direct dissolution method. Vasospasm of the CAM vessels was induced by means of ultrasound (Physiomed, continuous wave, 3MHz, 1.0W/cm2). The ultrasound-mediated nimodipine release (Physiomed, continuous wave, 1MHz, 1.7W/cm2) and its effect on the CAM vessels were evaluated. Measurements of vessel diameter before and after ultrasound-induced nimodipine release were performed using ImageJ. The CAM model could be successfully carried out in all 25 eggs. After vasospasm induction and before drug release, the mean vessel diameter was at 57% (range 44–61%) compared to the baseline diameter (set at 100%). After ultrasound-induced drug release, the mean vessel diameter of spastic vessels increased again to 89% (range 83–91%) of their baseline diameter, which was significant (p = 0.0002). We were able to provide a proof of concept for invivo vasos-pasm induction by ultrasound application in the CAM model and subsequent resolution by ultrasound-mediated nimodipine release from nanocarriers. This concept merits further evaluation in a rat SAH model.
Keywords: vasospam, SAB, chorioallantoic membran, aneurysm
 
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