RT Journal Article
T1 Remdesivir interactions with sulphobutylether-β-cyclodextrins: a case study using selected substitution patterns
A1 Piñeiro Guillén, Ángel
A1 Pipkin, James
A1 Antle, Vince
A1 García Fandiño, Rebeca
K1 Cyclodextrins
K1 Remdesivir
K1 ITC
K1 PMF
K1 Molecular dynamics
K1 Association constant
AB Modified cyclodextrins (CDs) consist of a distribution of different structures with different number and location of the substituted groups. Among the most important applications of these molecules is their use as an enabling excipient in pharmaceutical formulations to provide the necessary solubility, stability and bioavailability for a drug to be effectively used. The most typical interaction mechanism of small molecular groups with CDs is the formation of host–guest inclusion complexes. The thermodynamic affinity constant between CDs and drugs should not be too strong, since then the biological activity could be negated by the formation of the complex. In the opposite scenario, if the affinity constant is too weak, the complex is barely formed and the amount of CD required in the formulation may become too great. Thus, a balance between the affinity of the CD and the drug is necessary for an optimal formulation. Additionally in the case of modified CDs and specific drug complexes there are further questions concerning the effect that the locations and number of substitutions plays in complexation. In the present work, this question is explored by using sulphobutylether-β-cyclodextrin and remdesivir, the only antiviral medication currently approved by the United States Food and Drug Administration for treating COVID-19, as a case study. This paper presents results from an orthogonal study using isothermal titration calorimetry measurements and biased molecular dynamics simulations that provide complementary information. Isothermal titration calorimetry delves into the global impact of the species distribution while molecular dynamics simulations deals with specific chemical structures. The goal is to provide useful information to optimize pharmaceutical formulations based on modified CDs, specifically in the case of remdesivir, used to treat SARS-CoV-2 infection, although the main conclusions could be extended to the interaction of other drugs with modified cyclodextrins
PB Elsevier
YR 2022
FD 2022
LK http://hdl.handle.net/10347/27680
UL http://hdl.handle.net/10347/27680
LA eng
NO Journal of Molecular Liquids 346 (2022) 117157. https://doi.org/10.1016/j.molliq.2021.117157
NO R.G.-F thanks to the Spanish Agencia Estatal de Investigación (AEI) and the ERDF (RTI2018-098795-A-I00) and for a “Ramón y Cajal” contract (RYC-2016-20335), to Xunta de Galicia (ED431F 2020/05) and Centro singular de investigación de Galicia accreditation 2019-2022, ED431G 2019/03) and the European Union (European Regional Development Fund - ERDF). Á. P. thanks to the Ministerio de Ciencia e Innovación (PID2019-111327GB-I00). We thank the “Centro de Supercómputo de Galicia” (CESGA) for computing time as well as for their exceptional technical support
DS Minerva
RD 24 abr 2026