title: Influence of Ethanol as a Co-Solvent in Cyclodextrin Inclusion Complexation: A Molecular Dynamics Study.
abstract: Molecular dynamics (MD) simulations were used to investigate the dynamics and host-guest interactions of the inclusion complexes between a potent anti-HIV agent, UC781, and three different types of cyclodextrins (CDs) including βCD, 2,6-dimethyl-βCD (MβCD), and 2-hydroxypropyl-βCD (HPβCD) in aqueous solution with ethanol (EtOH) as a co-solvent. The MD simulation results revealed that EtOH as the co-solvent and the type of cyclodextrin affected the inclusion complex formation. From this study, UC781/MβCD provided the most stable inclusion complex. The competition for the cavity of βCD between UC781 and EtOH and the ensuing occupation of βCD cavities by EtOH resulted in a weaker interaction between βCD and UC781. In HPβCD, a supramolecular complex of UC781-HPβCD-EtOH was formed. The EtOH could easily fill the residual void space of the interior of unoccupied HPβCD due to the movement of UC781. In MβCD, the strong hydrogen bond interactions between the UC781 amide group and the secondary hydroxyl groups of MβCD significantly stabilized the inclusion complex in the presence of EtOH.
authors.affiliation: School of Bio-Chemical Engineering and Technology, Sirindhorn International Institute of Technology, Thammasat University, Pathum Thani 12121, Thailand.
authors.forename: Kanokthip
authors.initials: K
authors.lastname: Boonyarattanakalin
authors.affiliation: Department of Pharmaceutical Technology and Biopharmaceutics, Faculty of Life Sciences, University of Vienna, Althanstrasse 14, 1090 Vienna, Austria.
authors.forename: Helmut
authors.initials: H
authors.lastname: Viernstein
authors.affiliation: Department of Pharmaceutical Technology and Biopharmaceutics, Faculty of Life Sciences, University of Vienna, Althanstrasse 14, 1090 Vienna, Austria.
authors.forename: Peter
authors.initials: P
authors.lastname: Wolschann
authors.affiliation: School of Bio-Chemical Engineering and Technology, Sirindhorn International Institute of Technology, Thammasat University, Pathum Thani 12121, Thailand.
authors.forename: Luckhana
authors.initials: L
authors.lastname: Lawtrakul
keywords: Co-solvent; Cyclodextrin; Inclusion Complexation; Molecular Dynamics Simulation
references.citation: J Comput Chem. 2003 Dec;24(16):1999-2012
references.pmid: 14531054
references.citation: AAPS J. 2008 Dec;10(4):606-13
references.pmid: 19089644
references.citation: J Chem Theory Comput. 2007 Nov;3(6):2312-34
references.pmid: 26636222
references.citation: Eur J Pharm Sci. 2012 Nov 20;47(4):752-8
references.pmid: 22922099
references.citation: Biochemistry. 1997 Jun 24;36(25):7786-92
references.pmid: 9201921
references.citation: Mol Pharmacol. 1996 Aug;50(2):394-401
references.pmid: 8700148
references.citation: Antimicrob Agents Chemother. 2007 May;51(5):1608-15
references.pmid: 17353240
references.citation: Biochemistry. 1998 Oct 13;37(41):14394-403
references.pmid: 9772165
references.citation: Int J Pharm. 2013 Aug 30;453(1):167-80
references.pmid: 22771733
references.citation: Int J Pharm. 2002 Mar 2;234(1-2):113-9
references.pmid: 11839442
references.citation: AIDS. 1998 Jul 9;12(10):1129-38
references.pmid: 9677161
references.citation: Nat Rev Drug Discov. 2004 Dec;3(12):1023-35
references.pmid: 15573101
references.citation: J Virol. 1997 Apr;71(4):3023-30
references.pmid: 9060662
references.citation: Int J Pharm. 2003 Apr 30;256(1-2):85-94
references.pmid: 12695014
references.citation: Sex Transm Dis. 2008 Apr;35(4):414-9
references.pmid: 18362865
references.citation: Int J Pharm. 2007 Feb 1;329(1-2):1-11
references.pmid: 17137734