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

Shashi Chandrama Singh; Dharmendra Kumar Khatri; Kulbhaskar Singh; Vinay Kumar Kanchupalli; Jitender Madan; Shashi Bala Singh; Harshpal Singh

doi:10.1016/j.heliyon.2021.e07741

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

Heliyon. 2021 Aug;7(8):e07741. doi: 10.1016/j.heliyon.2021.e07741. Epub 2021 Aug 9.

Authors

Shashi Chandrama Singh¹, Dharmendra Kumar Khatri², Kulbhaskar Singh¹, Vinay Kumar Kanchupalli³, Jitender Madan⁴, Shashi Bala Singh², Harshpal Singh¹

Affiliations

¹ Research and Development Centre, Ambe Phytoextracts Private Limited, Pauri Garhwal, Uttarakhand, India.
² Department of Biological Sciences, National Institute of Pharmaceutical Education and Research, Hyderabad, India.
³ Department of Chemical Sciences, National Institute of Pharmaceutical Education and Research, Hyderabad, India.
⁴ Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, Hyderabad, India.

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; Antiviral; Bioavailability; Cyclodextrin; Pharmacokinetic; SARS-CoV-2.