title: Nose-to-brain transport of melatonin from polymer gel suspensions: a microdialysis study in rats.
abstract: OBJECTIVE
  Exogenous melatonin (MT) has significant neuroprotective roles in Alzheimer's and Parkinson's diseases. This study investigates the delivery MT to brain via nasal route as a polymeric gel suspension using central brain microdialysis in anesthetized rats.
  
  
  METHODS
  Micronized MT suspensions using polymers [carbopol, carboxymethyl cellulose (CMC)] and polyethylene glycol 400 (PEG400) were prepared and characterized for nasal administration. In vitro permeation of the formulations was measured across a three-dimensional tissue culture model EpiAirway(™). The central brain delivery into olfactory bulb of nasally administered MT gel suspensions was studied using brain microdialysis in male Wistar rats. The MT content of microdialysis samples was analyzed by high performance liquid chromatography (HPLC) using electrochemical detection. The nose-to-brain delivery of MT formulations was compared with intravenously administered MT solution.
  
  
  RESULTS
  MT suspensions in carbopol and CMC vehicles have shown significantly higher permeability across Epiairway(™) as compared to control, PEG400 (P < 0.05). The brain (olfactory bulb) levels of MT after intranasal administration were 9.22, 6.77 and 4.04-fold higher for carbopol, CMC and PEG400, respectively, than that of intravenous MT in rats. In conclusion, microdialysis studies demonstrated increased brain levels of MT via nasal administration in rats.
authors.affiliation: Department of Pharmacal Sciences, Harrison School of Pharmacy, Auburn University, Auburn, AL, USA. rjbabu68@gmail.com
authors.forename: R
authors.initials: R
authors.lastname: Jayachandra Babu
authors.forename: Pankaj Patrick
authors.initials: PP
authors.lastname: Dayal
authors.forename: Kasturi
authors.initials: K
authors.lastname: Pawar
authors.forename: Mandip
authors.initials: M
authors.lastname: Singh
mesh_terms: D000180:Acrylic Resins; D000281:Administration, Intranasal; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001692:Biological Transport; D002266:Carboxymethylcellulose Sodium / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D005782:Gels; D007275:Injections, Intravenous; D008297:Male; D008550:Melatonin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D017551:Microdialysis; D009830:Olfactory Bulb / Q000378:metabolism*; D010539:Permeability; D011092:Polyethylene Glycols / Q000737:chemistry; D011145:Polyvinyls / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000180:Acrylic Resins; D000975:Antioxidants; D005782:Gels; D011145:Polyvinyls; C006912:carboxypolymethylene; D011092:Polyethylene Glycols; D008550:Melatonin; D002266:Carboxymethylcellulose Sodium