Gold Nanoparticles: Tunable Characteristics and Potential for Nose to Brain Drug Delivery (NTBDD)

A general procedure to prepare gold nano-urchins (GNUs) via a seed-mediated method was followed using dopamine hydrochloride as a reducing agent and silver nitrate salt (AgNO3) as a shape-directing agent. The novelty of the present study comes from the successful incorporation of the prepared gold urchins in a form of an aqueous suspension in a nasal pressurized metered dose inhaler (pMDI) formulation and the potential of olfactory targeting for a direct nose-to-brain drug delivery (NTBDD) was investigated. The developed pMDI formulation is composed of 0.025 w//w GNUs, 2% w/w Milli-Q water, and 2% w/w EtOH of the total formulation with the balance of HFA134a propellant. The particle integrity and aerosolization performance using an aerosol exposure system, whereas the nasal deposition profile was tested in a sectioned anatomical replica of human nasal airways. The compatibility of the gold dispersion with the nasal epithelial cell line RPMI 2650 was also presented in this study. The gold colloidal was found to be stable following six-month storage at 4 °C and during the lyophilisation process utilising a pectin matrix for complete re-dispersibility in water. The GNUs were intact and discrete following atomization via a pMDI and 13% of the delivered particles were detected beyond the nasal valve, the narrowest region in the nasal cavity, out of which 5.6% was recovered from the olfactory region. Moreover, the formulation was found to be compatible with the human nasal epithelium cell line RPMI 2650 and excellent cell viability was observed. The formulated GNPs-HFA-based pMDI is a promising approach for a variety of NTBDD applications.