Nose-to-brain transport of melatonin from polymer gel suspensions: a microdialysis study in rats

R. Jayachandra Babu1, Pankaj Patrick Dayal2, Kasturi Pawar1, and Mandip Singh3, 1Department of Pharmacal Sciences, Harrison School of Pharmacy, Auburn University Auburn, AL, USA, 2Valeritas LLC, Research and Development, Shrewsbury, MA, USA, 3College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL, USA

PURPOSE: 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.


Intranasal administration, TEER, EpiAirway, nasal drug delivery, MTT

Materials Tested

PEG400, Carbopol, carboxymethyl cellulose, melatonin

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