Breaking Barriers: Intranasal Microemulsions for the Efficient Nose-to-brain Delivery of Glycyrrhetinic Acid

Abstract

Herbal drugs have been investigated for multiple neurodegenerative diseases because of their multi-targeted mechanisms of action and relatively low toxicity profile. However, due to their unfavorable physicochemical properties that limit their action, nanocarriers are warranted to enhance their delivery and hence their therapeutic effect. In this study, an intranasal microemulsion (ME) of the lipophilic molecule glycyrrhetinic acid (GA), a triterpenoid derived from licorice root that is widely known for its antioxidant and anti-inflammatory properties, was developed for the treatment of Alzheimer's disease (AD). Pseudo-ternary phase diagrams were constructed and the prepared ME systems were optimized using Simplex lattice mixture experimental design. The selected loaded lauroglycol MEs (GA-ME LG) were of droplet size 5.61 ± 0.01 nm and PDI of 0.521 ± 0.032. They showed a significantly high physical stability up to 3 months at room temperature and in the refrigerator. The ex vivo permeation study across sheep nasal mucosa revealed that GA-loaded ME LG exhibited a significant increase in steady-state flux after 8 h compared to GA suspension by 5.67-fold (p < 0.05). SCOP-induced memory impairment in rats was ameliorated by intranasal injection of GA ME LG at a concentration of 1 mg/kg, in a comparable way to the oral route (at a dosage 50 times higher than MEs) (p < 0.05). Additionally, GA ME LG counteracted SCOP-induced oxidative damage (p < 0.05). Collectively, GA-loaded MEs can deliver GA to the brain efficiently and might offer potential treatment for AD patients.