Pharmacokinetic of nasal curcumin:An approach for asthma medication

OBJECTIVE The study aims to evaluate intranasal(i.n.)curcumin at 5mg·kg-1,its absorption through nasal mucosa reaching blood and lungs and investigate its anti-allergic and anti-asthmatic potentiality in ameliorating ovalbumin induced asthma in mouse model.METHODS A simple and sensitive high performance liquid chromatography method using UV detection(HPLC-UV)was developed and validated for the determination of nasal curcumin 5mg·kg-1 in nasal mucosa,plasma and lungs from 15min-6hof post dosing and further applied to determine the pharmacokinetics parameter.Further,for the anti-asthmatic study,BALB/c mice were sensitized(day 1,7and 14)and challenged with ovalbumin(day 19-22)and treated with intranasal curcumin 5mg·kg-1(in the form of nasal drops)before an hour of challenge(day 19-22)to investigate its therapeutic effect on various parameters of airway inflammation as detected in the bronchoalveolar lavage fluid,serum and lung tissue.Serum was also used to study the liver kidney function test for the toxicity.RESULTS The validated method of HPLC was sensitive with a lower limit of quantitation of 5μg·mL-1 and the calibration curve represented good linearity(r2≥0.999)over the linear range of 5-50μg·mL-1.HPLC study reveals,absorption and quantification of curcumin as 1.9μg·mL-1 in the nasal mucosal scrapping at 15 min elevating to 4.9μg·mL-1 till 1h and declining to 3.2μg·mL-1 till 3h after intranasal administration of curcumin(5mg·kg-1).The plasma showed 0.9μg·mL-1 after 15 min spiking upto 1.5μg·mL-1 till 3h while lung homogenate retained up to 3.6μg·mL-1 of curcumin till 3h,which was detectable from 15min(0.27μg·mL-1)and was on higher side as compared to earlier studies.The same pharmacological dose(5mg·kg-1,i.n.)has shown anti-asthmatic potential by inhibiting airway inflammation(eosinophilic inflammation),bronchoconstriction and modulation in cytokines level of Th2(IL-4,IL-5),Th1(IFN-γ)and proinflammatory(TNF-α)cytokines in ovalbumin induced asthma without having any side effect as det