Abstract
Nose-to-brain (N2B) drug delivery is a promising technique for the treatment of brain diseases. It allows a drug to enter the brain without passing through the blood-brain barrier. However, the nasal cavity and nasal mucosa can restrict the amount of drug absorbed. Recent studies of non-thermal plasma (NTP) have shown improvement in in vitro drug delivery to cells and tissues. However, whether NTP treatments can enhance the in vivo delivery of drugs for neurodegenerative disease like Alzheimer's disease (AD) into the brain via the N2B technique remains unclear. The drug used in this study was galantamine hydrobromide. Galantamine is used to treat patients with mild to moderate AD. Based on the principle of NTP, a type of dielectric barrier discharge (DBD) plasma, which we called spiral DBD microplasma, was designed. It was inserted into the nose of a rat to a depth of 2 mm. The spiral DBD microplasma was driven by a sinusoidal voltage for 4 min, followed by the immediate administration of galantamine. The effect of the microplasma treatment on the distribution of galantamine in the brain was evaluated using matrix-assisted laser desorption/ionization-imaging mass spectrometry (MALDI-IMS). The results showed a high distribution of galantamine in the left and right brain hemispheres of the rat treated with plasma discharge compared to a control treated without plasma discharge. The spiral DBD microplasma is a novel contribution to DBD plasma designs. In addition, this technique for drug delivery has also created a novel approach with potential for becoming a non-invasive method of enhancing drug distribution in the brain for the treatment of neurological disorders.