Remdesivir interactions with sulphobutylether-β-cyclodextrins: A case study using selected substitution patterns

Aggregation versus inclusion complexes to solubilize drugs with cyclodextrins. A case study using sulphobutylether-β-cyclodextrins and remdesivir

“…The same three different representative structures of SBE-b-CD with a single substitution in the primary side and 4, 5 or 6 substitutions in the secondary size of the CD employed in our previous work (5SBE, 6SBE and 7SBE, Fig. 1) [24] were selected for the current simulations. For remdesivir, the previously employed neutral and protonated structures were used.…”

“…For remdesivir, the previously employed neutral and protonated structures were used. The parameterizations of the molecules and the employed general simulation methods were also identical to those of our previous publications [20,24,25]. Briefly, GROMACS 2020 package [26][27][28] was used to run the simulations in the NPT ensemble at 298 K and 1 bar with the 54a7 parameterization of the GROMOS force field [29] and the SPC water model [30], the v-rescale thermostat [31] and the Parrinello-Rahman barostat [32], the PME algorithm [33,34] for the long range interactions and a cutoff of 1.2 nm for the short range interactions.…”

“…It was observed that the drug remains solubilized upon the addition of NaOH at the proposed concentrations, thus allowing the administration of the formulation at neutral pH into the human body. We have recently reported a detailed thermodynamic and structural characterization on the formation of inclusion complexes between SBE-b-CD (considering different number and location of substitutions) and remdesivir at two different pH values by ITC measurements and molecular dynamics (MD) simulations [24]. Our results indicate that the association constant for the formation of the inclusion complexes is moderate ($10 4 M À1 ) at low pH and even lower ($10 2 M À1 ) at neutral pH.…”

Comparative bioavailability study following a single dose intravenous and buccal administration of remdesivir in rabbits

“…The role of SBECD is to improve both the solubility and stability of remdesivir via inclusion complex formation ( Pipkin et al, 2020 ). Molecular dynamic study proved the interaction between remdesivir and SBECD of various DS ( Garrido et al, 2020 ; Piñeiro et al, 2021 , Piñeiro et al, 2022 ). Recent NMR investigations suggested that the protonation state of the aminopyrrolo-triazine moiety of remdesivir can play a key role in the cyclodextrin-remdesivir interaction ( Várnai et al, 2022 ).…”

Entropy-Driven Inclusion of Natural Protoberberine Alkaloids in Sulfobutylether-β-Cyclodextrin

“…Despite the many applications of sulfobutylated βCD, few isothermal titration calorimetry studies have been performed to gain deeper insight into the factors controlling the strength of guest binding in its cavity [ 10 , 17 , 18 , 19 , 20 , 21 , 22 , 23 ]. The effect of systematic molecular structure variation on the thermodynamics of the inclusion of aromatic compounds in this macrocycle has not been examined.…”