Real-time observation of aortic vessel dilation through delivery of sodium nitroprusside via slow release mesoporous nanoparticles

Abstract

Spherical mesoporous nanoparticles (MNPs) with a diameter of ∼100nm were synthesised via a sol-gel method in the presences of organic template (with and without fluorescein dye encapsulation). The template molecules were removed by acidic extraction to form a regular pore lattice structure. The nanoparticle size and morphology were analysed using transmission electron microscopy and dynamic light scattering analysis. The MNPs were further characterised by zeta potential, nitrogen adsorption measurements and infra-red spectroscopy. The interior pores had an average diameter of ∼3nm and were loaded with an endothelial-independent vasodilator, sodium nitroprusside (SNP). The optimal drug loading and drug release was determined in high potassium physiological salt solution using dialysis and atomic absorption spectroscopy. We demonstrate that the initial instantaneous release is due to the surface desorption of the drug followed by diffusion from the pores. Furthermore, these drug loaded MNPs (with and without fluorescein dye encapsulation) were added to viable aortic vessels and release in real-time was observed, ex vivo. MNPs and loaded with and without SNP were incubated with the vessel (at 1.96×1012NPmL−1) over a 3h time period. The real-time exposure to unloaded MNPs resulted in a small attenuation in constriction that occurred after approximately 1h. In contrast, MNPs loaded with SNP led to a rapid relaxation of aortic vessels that was sustained over the 3h period (p<0.001).