235
Thomas Mavromoustakos et al. (eds.), Supramolecules in Drug Discovery and Drug Delivery: Methods and Protocols,
Methods in Molecular Biology, vol. 2207, https://doi.org/10.1007/978-1-0716-0920-0_18,
© Springer Science+Business Media, LLC, part of Springer Nature 2021
Chapter 18
2D DOSY NMR: A Valuable Tool to Confirm the Complexation
in Drug Delivery Systems
Christos M. Chatzigiannis, Sofia Kiriakidi, Andreas G. Tzakos,
and Thomas Mavromoustakos
Abstract
Many bioactive substances face the problem of limited bioavailability, mainly due to low aqueous solubility
and poor metabolic stability. Their complexation with drug delivery systems offers a more optimum pharmacological profile. Some of these drug delivery systems that have promising potential form complexes
with bioactive compounds such as cyclodextrins and calixarenes. The monitoring of the success and the
type of the complexation are of great importance and two-dimensional diffusion-ordered NMR spectroscopy (2D DOSY) is a valuable tool for the studying of these complexes and described as “NMR chromatography.” Herein we report the procedure for the complexation of the natural product quercetin in
2-hydroxypropyl-β-cyclodextrin and the anticancer drug temozolomide in p-sulfonatocalix[4]arene and
the determination of the complexation with 2D DOSY spectroscopy.
Key words Cyclodextrins, 2-Hydroxypropyl-β-cyclodextrin, Quercetin, Temozolomide, pSulfonatocalix[4]arene, Complex, Bioavailability, Diffusion-ordered NMR spectroscopy, 2D DOSY,
NMR spectroscopy
1 Introduction
Quercetin (QUE) is a flavonoid with low aqueous solubility
responsible for its poor absorption through the gastrointestinal
tract after oral administration. Besides, its extensive metabolism
through enzymatic processes such as glucuronidation, sulfation,
and methylation that take place mainly in the liver and the small
intestine leads to the formation of metabolites, characterized by
less bioactivity. During intravenous injection, quercetin may cause
local toxicity and other side effects that limit the administered
dose. To circumvent these problems is encapsulated in cyclodextrins [1–4] (Fig. 1).
Cyclodextrins and especially 2-hydroxypropyl-β-cyclodextrin
(HP-β-CD) (Fig. 1) have been widely used to protect drugs against
conjugation and metabolic inactivation as well as to enhance the
Thomas Mavromoustakos et al. (eds.), Supramolecules in Drug Discovery and Drug Delivery: Methods and Protocols,
Methods in Molecular Biology, vol. 2207, https://doi.org/10.1007/978-1-0716-0920-0_18,
© Springer Science+Business Media, LLC, part of Springer Nature 2021
Chapter 18
2D DOSY NMR: A Valuable Tool to Confirm the Complexation
in Drug Delivery Systems
Christos M. Chatzigiannis, Sofia Kiriakidi, Andreas G. Tzakos,
and Thomas Mavromoustakos
Abstract
Many bioactive substances face the problem of limited bioavailability, mainly due to low aqueous solubility
and poor metabolic stability. Their complexation with drug delivery systems offers a more optimum pharmacological profile. Some of these drug delivery systems that have promising potential form complexes
with bioactive compounds such as cyclodextrins and calixarenes. The monitoring of the success and the
type of the complexation are of great importance and two-dimensional diffusion-ordered NMR spectroscopy (2D DOSY) is a valuable tool for the studying of these complexes and described as “NMR chromatography.” Herein we report the procedure for the complexation of the natural product quercetin in
2-hydroxypropyl-β-cyclodextrin and the anticancer drug temozolomide in p-sulfonatocalix[4]arene and
the determination of the complexation with 2D DOSY spectroscopy.
Key words Cyclodextrins, 2-Hydroxypropyl-β-cyclodextrin, Quercetin, Temozolomide, pSulfonatocalix[4]arene, Complex, Bioavailability, Diffusion-ordered NMR spectroscopy, 2D DOSY,
NMR spectroscopy
1 Introduction
Quercetin (QUE) is a flavonoid with low aqueous solubility
responsible for its poor absorption through the gastrointestinal
tract after oral administration. Besides, its extensive metabolism
through enzymatic processes such as glucuronidation, sulfation,
and methylation that take place mainly in the liver and the small
intestine leads to the formation of metabolites, characterized by
less bioactivity. During intravenous injection, quercetin may cause
local toxicity and other side effects that limit the administered
dose. To circumvent these problems is encapsulated in cyclodextrins [1–4] (Fig. 1).
Cyclodextrins and especially 2-hydroxypropyl-β-cyclodextrin
(HP-β-CD) (Fig. 1) have been widely used to protect drugs against
conjugation and metabolic inactivation as well as to enhance the