Anionic Nanoparticle Carriers for Neuron-targeting of Synthetic and Protein Drugs

Nanoparticles (NPs) frequently are selected to deliver therapeutic agents due to their unique properties, which improve systemic delivery. Notably, the properties of NPs are highly tunable and enable cell-specific targeting of their payload in addition to protecting the therapeutic agent from clearance. For example, recent work demonstrated that anionic NPs selectively target neurons. This charge-based selectively enables several applications such as delivery therapeutics to peripheral neurons after organophosphorus exposure. To address the need for neuron-selective nanoparticles, we will synthesize and characterize anionic, monodisperse small unilamellar liposomes as potential vehicles to deliver therapeutics. Specifically, these liposomes will consist of neutral and negatively charged lipids. The wide selection of available lipids enables modification to achieve the desired zeta potential, between 0 and -40 mV. The nanoparticles’ hydrodynamic radius and zeta-potential will be measured to quantify intra- and inter-batch variation. Notably, therapeutic agents will be encapsulated in the liposome’s lumen during formation. The therapeutic loading efficiency will be measured using UV-HPLC, while a colorimetric assay will quantify the reaction kinetics of entrapped enzymes. Finally, the effects of temperature on liposome stability will be assessed by comparing metrics such as size, size distribution, and enzymatic activity at room temperature and 37°C.