Molecular encapsulation of andrographolide in 2-hydroxypropyl-β-cyclodextrin cavity: synthesis, characterization, pharmacokinetic and in vitro antiviral activity analysis against SARS-CoV-2

Abstract

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 x 10−3M. 1H 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 IC50 of 0.1-μg.mL−1 (E gene) and 0.29-μg.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.

Keywords

• Andrographolide
• Cyclodextrin
• SARS-CoV-2
• Pharmacokinetic
• Bioavailability
• Antiviral