A single-step aerosol process for in-situ surface modification of nanoparticles: Preparation of stable aqueous nanoparticle suspensions

• Single-step gas phase process for synthesis and in-situ surface modification of lipid nanoparticles.
• Surface modified nanoparticles exhibited improved suspension stability for an observed period of 30 days.
• Surface modified nanoparticles showed spherical morphology with layered structure and mobility diameters of 130–150 nm.
• Combination of electrostatic and steric effects in surface-modified nanoparticles gave maximum suspension stability.

HypothesisSurface modification of nanoparticles during aerosol or gas-phase synthesis, followed by direct transfer into liquid media can be used to produce stable water-dispersed nanoparticle suspensions.ExperimentThis work investigates a single-step, aerosol process for in-situ surface-modification of nanoparticles. Previous studies have used a two-step sublimation–condensation mechanism following droplet drying, for surface modification, while the present process uses a liquid precursor containing two solutes, a matrix lipid and a surface modifying agent. A precursor solution in chloroform, of stearic acid lipid, with 4 %w/w of surface-active, physiological molecules [1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1,2-dipalmitoyl-sn-glycero-3-phospho-(1′-rac-glycerol)-sodium salt (DPPG) or 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy (polyethylene glycol) 2000]-ammonium salt (DPPE-PEG)] was processed in an aerosol reactor at a low gas temperatures. The surface modified nanoparticles were characterized for morphology, surface composition and suspension properties.FindingsSpherical, surface-modified lipid nanoparticles with median mobility diameters in the range of 105–150 nm and unimodal size distributions were obtained. Fourier transform infra-red spectroscopy (FTIR) measurements confirmed the presence of surface-active molecules on external surfaces of modified lipid nanoparticles. Surface modified nanoparticles exhibited improved suspension stability, compared to that of pure lipid nanoparticles for a period of 30 days. Lowest aggregation was observed in DPPE-PEG modified nanoparticles from combined electrostatic and steric effects. The study provides a single-step aerosol method for in-situ surface modification of nanoparticles, using minimal amounts of surface active agents, to make stable, aqueous nanoparticle suspensions.

In-situ surface modification using an aerosol process, suppressed nanoparticle agglomeration, and consequent hydrodynamic diameter (HDD) increase, in aqueous suspension during 30-day period.Figure optionsDownload high-quality image (106 K)Download as PowerPoint slide