Upregulation of endogenous neurotrophin levels in the brain by intranasal administration of carnosic acid.

The potential of intranasally administered carnosic acid to enhance the endogenous levels of neurotrophins [nerve growth factor and brain-derived neurotrophic factor] in the brain was investigated. Hydroxypropyl-β-cyclodextrin (HP-β-CD) was used to enhance the aqueous solubility of carnosic acid. The effect of different concentrations of chitosan on the permeation of carnosic acid was investigated across the bovine olfactory mucosa using Franz diffusion cell setup. The formulations were administered [intranasal (i.n.)/subcutaneous route] in Sprague-Dawley rats, and the neurotrophins were sampled from the brain by microdialysis after the treatment period and measured by enzyme-linked immunosorbent assay. Phase solubility studies revealed that the solubility of carnosic acid was enhanced significantly with increase in the concentration of HP-β-CD. The neurotrophin levels were enhanced significantly upon i.n. administration of carnosic acid with chitosan, which was approximately 1.5-2-fold more over the parenteral route. Nose-to-brain delivery of carnosic acid along with chitosan is a potential approach for treating disorders associated with depletion of neurotrophins.