title: Upregulation of endogenous neurotrophin levels in the brain by intranasal administration of carnosic acid.
abstract: 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.
authors.affiliation: Department of Pharmaceutics, The University of Mississippi School of Pharmacy.
authors.forename: Siva Ram Kiran
authors.initials: SRK
authors.lastname: Vaka
authors.affiliation: Department of Pharmaceutics, The University of Mississippi School of Pharmacy. Electronic address: murthy@olemiss.edu.
authors.forename: S Narasimha
authors.initials: SN
authors.lastname: Murthy
authors.affiliation: Department of Pharmaceutics, The University of Mississippi School of Pharmacy; The National Center for Natural Products Research, The University of Mississippi, Mississippi 38677.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Repka
authors.affiliation: Department of Pathology, College of Veterinary Medicine, University of Georgia, Athens, Georgia 30602.
authors.forename: Tamas
authors.initials: T
authors.lastname: Nagy
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D045784:Abietanes / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D000281:Administration, Intranasal; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis*; D002417:Cattle; D048271:Chitosan / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry; D005079:Excipients / Q000737:chemistry; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D066298:In Vitro Techniques; D017551:Microdialysis; D015394:Molecular Structure; D020932:Nerve Growth Factor / Q000096:biosynthesis*; D009831:Olfactory Mucosa / Q000378:metabolism*; D010936:Plant Extracts / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D015854:Up-Regulation; D047392:beta-Cyclodextrins / Q000737:chemistry
chemical_list: D045784:Abietanes; D019208:Brain-Derived Neurotrophic Factor; D004337:Drug Carriers; D005079:Excipients; D010936:Plant Extracts; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D048271:Chitosan; D020932:Nerve Growth Factor; C018381:salvin