In present investigation, AND-2-HyP-
β
-CYD (Andrographolide-2-Hydroxypropyl-
β
-cyclodextrin) complex was synthesized and characterized for antiviral and pharmacokinetic profile. The linear host-guest relation suggested synthesis of a 1:1 complex of AND with 2-HyP-
β
-CYD by inclusion mode. The Kc, stability constant of the two phase system of AND with 2-HyP-
β
-CYD computed to be 38.60.x10
-3
M.
1
H NMR spectrum of AND indicated the presence of triplet at 6.63-ppm which was up-fielded in AND-2-HyP-
β
-CYD complex at 6.60-ppm (doublet) confirmed the insertion of AND in cavity of 2-HyP-
β
-CYD through lactone ring. AND-2-HyP-β-CYD complex exhibited the IC
50
of 0.1-
μ
g.mL
-1
(E gene) and 0.29-
μ
g.mL
-1
(N gene) against SARS-CoV-2 infected Vero6 cells. Moreover, a 1.5-fold increment in extent of absorption of AND was noticed post complexation.The bioavailability was estimated to be 15.87±3.84% and 23.84±5.46%, respectively for AND and AND-2-HyP-
β
-CYD complex. AND-2-HyP-
β
-CYD complex may be a prospective candidate for further studies to evolve as a clinically viable formulation against SARS-CoV-2.
Objective. Acute and subacute toxicity analysis of AND-2-HyP-β-CYD complex was conducted in Sprague-Dawley (SD) rats following oral and inhalation routes of administration. Methods and Results. Single dose acute toxicity was carried out at 2000 mg/kg of AND-2-HyP-β-CYD complex, while the doses of 200, 400, and 666 mg/kg were administered, over a period of 28 days under repeated dose oral toxicity study. Hence, LD50 (lethal dose) was found to be >2000 mg/kg in addition to NOAEL (no observed adverse effect level) of 666 mg/kg. Correspondingly, single dose acute inhalation toxicity of AND-2-HyP-β-CYD complex was carried out at 5 mg/L/4 h/day and subacute inhalation toxicity at 0.5, 1, and 1.66 mg/L/4 h/day over a period of 28 days. The NOAEL and LOAEL (lowest observed adverse effect level) were estimated to be 0.5 mg/L/4 h/day and 1 mg/L/4 h/day, respectively. Conclusion. The findings of the present study would further be useful in assessing and utilizing the medicinal and therapeutic benefits of AND-2-HyP-β-CYD complex.
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