title: Interaction of artesunate with β-cyclodextrin: Characterization, thermodynamic parameters, molecular modeling, effect of PEG on complexation and antimalarial activity.
abstract: Inclusion of artesunate in the cavity of β-cyclodextrin (β-CD) as well as its methyl and hydroxypropyl derivatives was investigated experimentally and by molecular modeling studies. The effect of PEG on the inclusion was also studied. A 1:1 stoichiometry was indicated by phase-solubility studies both in the presence and absence of PEG and suggested by the mass spectrometry. The mode of inclusion was supported by 2D NMR and results were further verified by docking studies utilizing Fast Rigid Exhaustive Docking acronym. The thermodynamic parameters were determined for both binary and ternary systems using solution calorimetry and were found to be best for the methyl-β-cyclodextrin (Me-β-CD) system. However, the presence of PEG improves the complexation ability as evident from elevation in the numerical value of the stability constant (K). Solubility and dissolution profile of binary complex is enhanced in the presence of PEG, which is approximately at par with drug Me-β-CD complexes. In vivo studies showed 100% survivability in artesunate-Me-β-CD complexes.
authors.affiliation: University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160014, India.
authors.forename: Renu
authors.initials: R
authors.lastname: Chadha
authors.affiliation: University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160014, India.
authors.forename: Sushma
authors.initials: S
authors.lastname: Gupta
authors.affiliation: Department of Microbiology, Panjab University, Chandigarh 160014, India.
authors.forename: Geeta
authors.initials: G
authors.lastname: Shukla
authors.affiliation: Department of Chemistry, Panjab University, Chandigarh 160014, India.
authors.forename: D V S
authors.initials: DV
authors.lastname: Jain
authors.affiliation: Department of Pharmaceutical Chemistry, Bombay College of Pharmacy, Mumbai 400098, India.
authors.forename: Raghuvir R S
authors.initials: RR
authors.lastname: Pissurlenkar
authors.affiliation: Department of Pharmaceutical Chemistry, Bombay College of Pharmacy, Mumbai 400098, India.
authors.forename: Evans C
authors.initials: EC
authors.lastname: Coutinho
keywords: Artesunate; In vivo studies; Inclusion complexes; Molecular modeling; Thermodynamic parameters; β-Cyclodextrin and its derivatives