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Published on: November 14, 2018
Brain delivery of vasoactive intestinal peptide (VIP) following nasal administration to rats
Christine Dufes1, Jean-Christophe Olivier, Frédéric Gaillard
1Equipe émergente Médicaments Anti-infectieux et Barrière Hématoencéphalique, Laboratoire de Pharmacie Galénique et Biopharmacie, Faculté de Médecine et de Pharmacie, 34 rue du Jardin des Plantes, BP199, 86005 Poitiers Cedex, France.
Abstract:
The aim of this work was to study in rats the nasal route for the brain delivery of the vasoactive intestinal peptide (VIP) neuropeptide. After evaluating VIP stability in solutions obtained from nasal washes, the effect of formulation parameters (pH 4-9, 0-1% (w/v) lauroylcarnitine (LC), hypo- or isoosmolality) on the brain uptake of intranasally administered VIP (10(-8)M)/125I-VIP (300,000 cpm/ml) was studied, using an in situ perfusion technique. Brain radioactivity distribution was assessed by quantitative autoradiographic analysis. Results were compared to intravenously administered VIP. With a hypotonic formulation at pH 4 containing 0.1% LC and 1% bovine serum albumin, VIP stability was satisfactory and loss by adsorption was minimal. Using this formulation, around 0.11% of initial radioactivity was found in the brain after 30 min perfusion and was located in the olfactory bulbs, the midbrain and the cerebellum. HPLC analysis of brain and blood extracts demonstrated the presence of intact VIP in brain and its complete degradation in the blood compartment. By intravenous administration, no intact VIP was found either in brain or in blood. In conclusion, intact VIP could be delivered successfully to the brain using the intranasal route for administration.
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