15. Sustained Agrin Nanoparticle Delivery Improves Neuromuscular Junction Reinnervation and Functional Recovery after Chronic Denervation

Abstract

by their duration of effect, necessitating frequent redosing. We aim to develop a nanoparticle-based delivery system to extend BoNT release and characterize its release profile. METHODS:Botulinum toxin A (BoNTa) neuromodulators were encapsulated within polymeric nanoparticles (NPs) using a kinetically controlled microfluidic assembly method. Dynamic light scattering was used to measure particle size and uniformity. ELISA was used to quantify the protein release profile. RESULTS:Particle sizes were uniform with most particles centered at 100nm and nearly all particles between 50-200nm. A tunable release profile was achieved, in which BoNTa could be released linearly or with an initial bolus followed by sustained release at the desired rate. Reproducibility of NP performance was demonstrated in 3 independent trials. Our early in-vivo and mechanistic studies have demonstrated preservation of toxin bioactivity and extended therapeutic effect in a rat model. CONCLUSIONS:We developed a novel nanoparticle-based Botox formulation capable of providing long-acting release of neuromodulator with tunable kinetics at designated dosage. This sustained release delivery modality enables superior therapeutic outcomes with less frequent re-dosing.