Ex vivo and in vivo evaluation of an in situ nanogel composite loaded with carmustine: implications for efficient nose-to-brain delivery.

Abstract

In this study, the efficacy of a Nanogel Composite was evaluated and compared to the conventional drug carmustine (BCNU) through ex vivo and in vivo studies using New Zealand White rabbits. The Nanogel Composite is a thermosensitive, electro-responsive, and mucoadhesive gel containing BCNU-loaded paramagnetic nanoparticles known as Nano-co-Plex (NCP). Following intranasal administration, electrical stimulation (ES) was applied to the rabbit's nasal cavity, initiating the release of BCNU-NCP. Subsequently, a magnetic headband placed on the rabbit's head rapidly attracted the released nanoparticles toward the brain. The in vivo results showed high amount of BCNU in cerebrospinal fluid (CSF) and the brain of the rabbit for Nanogel Composite compared to the conventional drug with BCNU concentration values in the CSF, brain and plasma being 0.2571 µg/mL, 0.199 µg/g and 0.0078 µg/mL, respectively, after 30 min of administration with the application of ES and MF; and 0.0087 µg/mL, 0.0076 µg/g and 0.0078 µg/mL without the application. The system enabled a pulsatile 'on-off' release profile, improving drug localization in the brain while minimizing systemic exposure. The applied ES and MF conditions (5 V and 0.4 Tesla) were found to be safe and well-tolerated, indicating the potential of this dual-stimuli-responsive platform for effective, non-invasive, and controlled nose-to-brain drug delivery.