Nanocarrier Aided Nasal Vaccination: An Experimental and Computational Approach

Abstract

In the present study, an experimental and theoretical investigation on the nasal vaccine delivery is reported. Poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs) containing a model antigen, i.e., ovalbumin (OVA), and an adjuvant, i.e., monophosphoryl lipid A (MPLA), were prepared for nasal vaccine delivery. The nanoparticles, prepared by the double emulsion method, had an average particle size in the range of 296−401 nm and a zeta potential value of −14.3 to −23.2 mV. Depending on the initial OVA and MPLA concentrations in the recipe, the corresponding loadings varied from 1.07 to 10.16 wt % and from 0.177 to 1.081 wt %, respectively. The PLGA nanoparticles were found to be stable during their storage in a 9 wt % sucrose solution at 4 °C for 4 weeks. Examination of the OVA release profile from the PLGA nanoparticles in a physiological buffer solution (PBS) at 37 °C revealed an initial fast release of OVA located in the nanoparticles external surface area, followed by a lag phase of minimum release and a subsequent continuous release profile. The delivery and deposition of carrier droplets, containing PLGA nanoparticles, to the nasal cavity was determined using computational fluid dynamics (CFD) for steady-state inspiration and inlet velocities (vin) in the range of 1−20 m/s. Deposition efficiencies and spatial deposition distributions were found to be strongly dependent on the droplet size and volumetric flow rate. A nanoparticle release model was developed to determine the amount of nanoparticles delivered from the deposited carrier droplets to the nasal cavity surface by taking into account the droplet formation size and the residence time of deposited droplets in the nasal cavity. It was found that the average droplet size increased when the viscosity of the liquid droplet increased or the surface tension decreased, leading to longer residence times and, thus, to higher nanoparticle release rates from the deposited droplets.