Complexation of Doxorubicin with β and γ-Cyclodextrins

Abstract

The binding of β and γ-cyclodextrins with the anti-cancer drug doxorubicin has been examined with the use of fluorescence and absorbance spectroscopy, circular dichroism measurements, and proton NMR spectroscopy. The stoichiometry of the complexes formed and their apparent formation constants have been estimated with the use of various approaches. The stoichiometrics for both the β-cyclodextrin-doxorubicin complex and the γ-cyclodextrin-doxorubicin complex have been determined to be predominantly 1:1. The strength of the interaction of the drug with γ-cyclodextrin is stronger than that with β-cyclodextrin. The effect of varying the pH on the calculated formation constants of the complexes has also been investigated.

Effects of γ- and Hydroxypropyl-γ-cyclodextrins on the Transport of Doxorubicin across an in Vitro Model of Blood-Brain Barrier

“…The ␥-or HP-␥-CD has been used to modify the transport of DOX across the BBB. In aqueous medium, ␥-CD forms an inclusion complex with DOX as proved by NMR (Djedaïni et al, 1990), fluorescence (Husain et al, 1992), and absorbance spectroscopy (Bekers et al, 1990). The stoichiometry has been determined to be 1:1, and the association constant value differed according to experimental technique varying between 200 and 1000 M Ϫ1 .…”

DMEM (Dulbecco’s Modified Eagle’s Medium)

“…The γ-or HP-γ-CD has been employed in order to modify the transport of DOX across the BBB. In aqueous medium, γ-CD forms an inclusion complex with DOX as proved by NMR (Djedaïni et al, 1990), fluorescence (Husain et al, 1992) and absorbance spectroscopy (Bekers et al, 1990). The stoichiometry has been determined to be 1:1 and the association constant value differed according to experimental technique varying between 200 and 1000 M -1…”

Soluble cyanine dye/β-cyclodextrin derivatives: Potential carriers for drug delivery and optical imaging

“…As a consequence, the emission intensity of Dox during titrations with derivatives of 1 (or 2) was corrected to remove their fluorescence and/or to take into account the fact that a fraction of the incident light is absorbed by βCyD derivatives at the Dox excitation wavelength of (470 nm). Although Dox's complexation with native βCyD usually causes a decrease in intensity with [βCyD], [29], an increase takes place in this case as a consequence of the overlap of the emission spectra of Dox and 1. It was thus necessary to perform a correction which was carried out using a fraction of M A N U S C R I P T…”

“…[28] The stabilization of anthracycline drugs can also be achieved via their complexation with CyD carriers. [29][30][31][32][33] However, one of the main restrictions on the use of CyD as an anthracycline carrier is the fact that the complexes formed show lower stability constants than the drug−DNA complex. [34] CyD chemical modification, by covalently attaching the appropriate moieties, can substantially increase the stability of the CyD-drug complex and such measures have been taken as a means for making complex-controlled target drug carriers.…”