Co-solvation effect on the binding mode of the α-mangostin/β-cyclodextrin inclusion complex

Abstract

SummaryCyclodextrins (CDs) have been extensively utilized as host molecules to enhance the solubility, stability and bioavailability of hydrophobic drug molecules through the formation of inclusion complexes. It was previously reported that the use of co-solvents in such studies may result in ternary (host:guest:co-solvent) complex formation. The objective of this work was to investigate the effect of ethanol as a co-solvent on the inclusion complex formation between α-mangostin (α-MGS) and β-CD, using both experimental and theoretical studies. Experimental phase-solubility studies were carried out in order to assess complex formation, with the mechanism of association being probed using a mathematical model. It was found that α-MGS was poorly soluble at low ethanol concentrations (0–10% v/v), but higher concentrations (10–40% v/v) resulted in better α-MGS solubility at all β-CD concentrations studied (0–10 mM). From the equilibrium constant calculation, the inclusion complex is still a binary complex (1:1), even in the presence of ethanol. The results from our theoretical study confirm that the binding mode is binary complex and the presence of ethanol as co-solvent enhances the solubility of α-MGS with some effects on the binding affinity with β-CD, depending on the concentration employed.

Metadynamics supports molecular dynamics simulation-based binding affinities of eucalyptol and beta-cyclodextrin inclusion complexes

“…The structures of bCD and its derivatives complexed with eucalyptol in aqueous solution were simulated with three different initial velocities by MD simulations utilizing the standard procedure applied to biomolecular systems [55][56][57][58] using the AMBER14 soware package. 59 bCD and its dimethyl and hydroxypropyl derivatives were treated using the Glycam-06h carbohydrate force eld.…”

<p>Nanoparticle Drug Delivery Systems for α-Mangostin</p>

“…[6][7][8][9][10][11][12][13][14][15][16][17][18] However, αmangostin has low solubility in water (2.03 x 10 −4 mg/L at 25ºC), and many efforts have been made to improve it: structure modification, co-solvation, solid dispersion, emulsion, complexation and nanoparticle drug delivery systems. [19][20][21] Additionally, αmangostin and other cytotoxic drugs generally have limitations that influence their effectiveness, including a first fast metabolism reaction, an efflux reaction induced by transporter intercellular, fast drug release and a non-specific target site. [22][23][24] Drug bioavailability is an important parameter to determine how successful the drug molecules pass through in pharmacological phases such as biopharmaceutics, pharmacokinetics, and pharmacodynamics.…”

“…Several types of nanoparticles have been formulated for the α-mangostin compound, including nanolipids, nanopolymerics, nanomicelles, nanoliposomes, nanofibers and metal nanoparticles. 19,20,[30][31][32][33][34] The results are substantial, with significantly improved solubility for α-mangostin. Therefore, controlled and targeted drug delivery systems can be created by modified nanoparticle technology.…”

Effect of Cyclodextrin Types and Co-Solvent on Solubility of a Poorly Water Soluble Drug

“…However, a destabilizing effect on CDs complexation, caused by co-solvents, has also been reported [18]. Two mechanisms have been discussed: firstly, the co-solvent can influence the polarity of the medium [19].…”