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.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.

Tenofovir antiviral drug solubility enhancement with β-cyclodextrin inclusion complex and in silico study of potential inhibitor against SARS-CoV-2 main protease (Mpro)

“…Additionally, the PatchDock and FireDock servers were used to research the protein and small molecule interactions of the β-CD:TFR inclusion complex with SARS-CoV-2 (M Pro ) protease inhibitors [52] , [53] , [54] , [55] , [56] . The results are shown in Fig.…”

Andrographolide/Phospholipid/Cyclodextrin Complex-Loaded Nanoemulsion: Preparation, Optimization, <i>in Vitro</i> and <i>in Vivo</i> Evaluation

“…The synthesized AHPC significantly enhanced the solubility of AG in the solutions with different pH. Ren et al 30) and Singh et al 31) have prepared AG-CD complex and noted that the solubility of AG has a linear relationship with the concen-tration of CD, the lineal host-guest correlativity with slope (<1) advised synthesis of a 1 : 1 ratio complex of AG with CD. Zhang et al 32) have prepared AG-CD complex with an increased solubility of AG by approximately 31 folds.…”

Acute and Subacute Toxicity Assessment of Andrographolide-2-hydroxypropyl-β-cyclodextrin Complex via Oral and Inhalation Route of Administration in Sprague-Dawley Rats

“…Three female rats with average age of 6-7 weeks were used for single dose acute oral toxicity analysis. In brief, AND-2-HyP- β -CYD complex [ 10 ] at the dose of 2000 mg/kg was administered to female rats through the oral route of administration according to OECD guideline 423 [ 13 ]. Animals were closely observed initially every 4 h, followed by once a day for a period of 14 days for any signs of toxicity or mortality, such as occurrence of lacrimation, changes in pupil size, and presence of an unusual respiratory pattern along with response to handling, as well as presence of clonic or tonic movements, stereotypes, or bizarre behaviour [ 14 ].…”

“…Previously, we have synthesized and characterized andrographolide-2-hydroxypropyl- β -cyclodextrin (AND-2-HyP- β -CYD) complex to augment the bioavailability of phytomolecules [ 10 ]. Thus, the evaluation of toxicity profile of AND-2-HP- β -CYD complex through oral and inhalation routes seems to be important and needs to be further studied.…”