Formulation and characterization of 6,6′-dihydroxythiobinupharidine and phloroglucinol nanoemulsion for intranasal approach to neurodegenerative disorders

Neurodegenerative diseases involve complex pathological mechanisms, including oxidative stress and neuroinflammation, which are not adequately addressed by single-target therapies. Therefore, a dual-targeted strategy is to be employed by combining phloroglucinol, a potent antioxidant, with 6,6′-dihydroxythiobinupharidine, a selective protein kinase C inhibitor. Thus, the present study aimed to formulate and evaluate phloroglucinol and 6,6′-dihydroxythiobinupharidine nanoemulsion (NE) for intranasal administration and a dual-targeted approach. NE was formulated using coconut oil, Span80, Tween80 and PEG400 in the ratio of 4.5:4.5:5.5:5.5. After formulation, it was evaluated for size, shape, drug release and stability. NE was homogenously opaque white and clear i.e., without any visible drug particles. It was an oil-in-water type of NE with a circular shape and size of <150 nm. It possessed a polydispersity index of 0.238, a zeta potential of -26.2 mV and was stable for more than 90 days. It was readily dispersible upon addition of water and showed no separation of oil and water. There was no sign of precipitation or cracking and exhibited a percentage transmittance of 93.4 ± 0.67. Nanoemulsified phloroglucinol and 6,6′-dihydroxythiobinupharidine had a cumulative release rate of 88.79 ± 1.92 and 90.39 ± 1.26, respectively, after 2 hr and 1 hr. Over 90 days, an increase in the particle size and a faint odor were observed. Therefore, these results indicate that the NE of phloroglucinol and 6,6′-dihydroxythiobinupharidine enables efficient and targeted delivery of drugs directly to the brain and improves treatment effectiveness for neurodegenerative disorders.