Dependence of Viscosity and Diffusion on β-Cyclodextrin and Chloroquine Diphosphate Interactions

Aleš Mráček,Lenka Musilová,Miguel A. Esteso,M. Melia Rodrigo,Artur J. M. Valente,Eduarda F. G. Azevedo,Ana C. F. Ribeiro

doi:10.3390/pr9081433

Abstract

Mutual diffusion coefficients of chloroquine diphosphate (CDP) in aqueous solutions both without and with β-cyclodextrin (β-CD) were measured at concentrations from (0.0000 to 0.0100) mol dm−3 and 298.15 K, using the Taylor dispersion technique. Ternary mutual diffusion coefficients (Dik) measured by the same technique are reported for aqueous CDP + β-CD solutions at 298.15 K. The presence of β CD led to relevant changes in the diffusion process, as showed by nonzero values of the cross-diffusion coefficients, D12 and D21. β-CD concentration gradients produced significant co-current coupled flows of CDP. In addition, the effects of β-CD on the transport of CDP are assessed by comparing the binary diffusion coefficient of aqueous CDP solutions with the main diffusion coefficient (D11) measured for ternary {CDP(1) + β-CD(2)} solutions. These observations are supported by viscosity analysis. All data allow to have a better interpretation on the effect of cyclodextrin on the transport behavior of CDP.

Highlights

The values found for D22 are similar to those of the binary diffusion coefficients reported for β-CD in aqueous solution [27]. These results indicate that while the addition of Chloroquine diphosphate (CDP) produces relatively small changes in the diffusion coefficient of β-CD (D22 ), the addition of β-CD leads to important changes in that of CDP (D11 )
We can conclude that the diffusion of the CDP is influenced by the presence of this macromolecular cyclodextrin (β-CD), suggesting that at low concentrations of this drug there is a very weak interaction between these solutes (which is supported by the small value that can be estimated for the equilibrium constant of the complexation between both solutes, CDP and β-CD, K = (30 ± 0.8) mol−1 dm3 )
This result is consistent with weak chloroquine binding to cyclodextrin, in contrast to a recent report of anomalously large-chloroquine binding constants

Summary

Introduction

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Chloroquine diphosphate (CDP) is a 4-aminoquinoline-based drug with a broad spectrum of applications, including all types of malaria infections and averse to cell growth and/or inducing cell death in human leukemia K562 cell [1,2,3]. CDP is indicated for the treatment of inflammatory diseases and rheumatoid arthritis [4,5]. CDP has been highly cited as a consequence of its potential, though not confirmed, to treat severe acute respiratory syndrome coronavirus 2 [6]

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Discussion

Conclusion