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Ultrasound-induced drug release from nimodipine-loaded nanoparticles – in-vivo analysis using the chicken chorioallantoic membrane model
Ultraschall-induzierte Medikamentenfreisetzung von mit Nimodipin geladenen Nanopartikel – in vivo Analysen am CAM-Modell
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Published: | June 4, 2021 |
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Objective: Nimodipine has been demonstrated to reduce ischemic complications following subarachnoid hemorrhage (SAH). In order to overcome the fist-pass effect of nimodipine, nanocarrier systems with sustained local drug delivery have gained increasing interest. The aim of this study is to produce nimodipine-loaded polymers and to evaluate the possibility of controlled drug release by applying ultrasound in the chicken chorioallantoic membrane (CAM) model.
Methods: Nimodipine-loaded nanoparticles were produced with Pluronic® F127 by the direct dissolution method. Vasospasm was induced by direct ultrasound-application (Physioson, 3 MHz, 1.0 W/cm2) for 60 seconds. The drug release from was performed by means of ultrasound (1 MHz, 1.7 W/cm²). The effect on the vessels was evaluated with the CAM-model. Nimodipine-loaded nanoparticles were applied in the control group without and in the treatment group with ultrasound application. The vessel diameter before and after treatment was visualized and measured using ImageJ.
Results: The ultrasound-induced nimodipine-release was evaluated on 20 embryo eggs (10 treatment group, 10 control). We found no change in the vessel diameter over time in the control group. The mean relative reduction in vessel diameter after vasospasm induction was 46% (range 44-56%). Eight minutes after ultrasound-induced nimodipine-release in the treatment group the mean vessel diameter of spastic vessels increased again to 90% (range 83-91%) of the initial diameter, which was statistically significant (t-test, p=0.0002).
Conclusion: A controlled drug release from nimodipine-loaded nanoparticles could be reliably induced by applying low frequency continuous wave ultrasound, which resulted in a significant vasospasm reduction in the CAM-model. These results are encouraging further evaluation of this treatment concept with intrathecal application of nimodipine-loaded nanoparticles in an animal SAH-model for controlled vasospasm resolution.