Ultrasound-induced release of nimodipine from drug-loaded block copolymers: In vitro analysis

Abstract Rationale Administration of nimodipine has been demonstrated to prevent secondary ischemic complications following subarachnoid hemorrhage and to improve functional outcome. Nanocarriers have been increasingly used for intrathecal nimodipine delivery with sustained drug release. However, no technique for an on-demand drug release at the time of vasospasm development has been established yet. The aim of this in vitro study was to produce nimodipine-loaded copolymers and to evaluate the possibility of on-demand drug release by means of ultrasound. Methods The copolymers were produced using Pluronic® F-127, and then loaded with nimodipine by applying the direct dissolution method. The drug release profile of bound nimodipine to copolymers was assessed using the dialysis bag method. The spontaneous as well as the ultrasound-guided (1 MHz with 1.7 W/cm2) drug-release was evaluated. Results A significant increase in nimodipine-release could be induced on-demand by ultrasound application for 30 or 60 s. While the maximum induced drug-release rate 24 h post treatment compared to the spontaneous drug-release rate was higher in the 5% and 15%-solution (p = 0.004), this was not the case in the 10%-solution. Comparing the two treatment durations, a higher drug-release was found in the 5% and 10%-solution after 5 min (p = 0.0002), 15 min (p = 0.0005) and 30 min (p = 0.0003) in the group receiving 60 s sonication. Conclusions By using the direct dissolution method, small-sized block copolymers comprising Pluronic® F-127 and nimodipine were successfully produced. In vitro analyses revealed that a significant increase in nimodipine-release rate could be efficiently induced on-demand after application of ultrasound for 60 s.