Investigation of Praziquantel/Cyclodextrin Inclusion Complexation by NMR and LC-HRMS/MS: Mechanism, Solubility, Chemical Stability, and Degradation Products

Špehar, Tatjana Kezele; Pocrnić, Marijana; Klarić, David; Bertoša, Branimir; Čikoš, Ana; Jug, Mario; Padovan, Jasna; Dragojević, Snježana; Galić, Nives

doi:10.1021/acs.molpharmaceut.1c00716

Cited by 12 publications

(2 citation statements)

References 39 publications

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“…This value is consistent with previous experimental results on a similar organic molecule (tryptophan) trapped in a clay-based material ( D ∼ 5 × 10 −11 cm 2 s −1 ) [46]. It is five orders of magnitude smaller than the diffusion coefficient of praziquantel dissolved in water [47,48].…”

Section: Drug Adsorbed In the Clay's Interlayer Spacesupporting

confidence: 92%

Kinetics of Drug Release from Clay Using Enhanced Sampling Methods

2022

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A key step in the development of a new drug, is the design of drug–excipient complexes that lead to optimal drug release kinetics. Computational chemistry and specifically enhanced sampling molecular dynamics methods can play a key role in this context, by minimizing the need for expensive experiments, and reducing cost and time. Here we show that recent advances in enhanced sampling methodologies can be brought to fruition in this area. We demonstrate the potential of these methodologies by simulating the drug release kinetics of the complex praziquantel–montmorillonite in water. Praziquantel finds promising applications in the treatment of schistosomiasis, but its biopharmaceutical profile needs to be improved, and a cheap material such as the montmorillonite clay would be a very convenient excipient. We simulate the drug release both from surface and interlayer space, and find that the diffusion of the praziquantel inside the interlayer space is the process that limits the rate of drug release.

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Section: Drug Adsorbed In the Clay's Interlayer Spacesupporting

confidence: 92%

Kinetics of Drug Release from Clay Using Enhanced Sampling Methods

2022

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“…CD complexes can be used to release biologically active compounds under specific conditions [ 31 , 32 , 33 ]. A recent study showed that the complexation with β-CD enhanced the therapeutic efficiency of praziquantel from 59% (for the plain drug) to 99% (for the β-CD complex) [ 34 ]. Moreover, studies with the essential oil of ocimum plant showed a low absorption giving a maximum % inhibition of edema equal to of 16%, while after its complexation with SBE-β-CD/HP-β-CD a higher absorption was observed achieving more than 50% inhibition of edema [ 35 ].…”

Section: Introductionmentioning

confidence: 99%

Comparative Interaction Studies of Quercetin with 2-Hydroxyl-propyl-β-cyclodextrin and 2,6-Methylated-β-cyclodextrin

et al. 2022

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Quercetin (QUE) is a well-known natural product that can exert beneficial properties on human health. However, due to its low solubility its bioavailability is limited. In the present study, we examine whether its formulation with two cyclodextrins (CDs) may enhance its pharmacological profile. Comparative interaction studies of quercetin with 2-hydroxyl-propyl-β-cyclodextrin (2HP-β-CD) and 2,6-methylated cyclodextrin (2,6Me-β-CD) were performed using NMR spectroscopy, DFT calculations, and in silico molecular dynamics (MD) simulations. Using T1 relaxation experiments and 2D DOSY it was illustrated that both cyclodextrin vehicles can host quercetin. Quantum mechanical calculations showed the formation of hydrogen bonds between QUE with 2HP-β-CD and 2,6Μe-β-CD. Six hydrogen bonds are formed ranging between 2 to 2.8 Å with 2HP-β-CD and four hydrogen bonds within 2.8 Å with 2,6Μe-β-CD. Calculations of absolute binding free energies show that quercetin binds favorably to both 2,6Me-β-CD and 2HP-β-CD. MM/GBSA results show equally favorable binding of quercetin in the two CDs. Fluorescence spectroscopy shows moderate binding of quercetin in 2HP-β-CD (520 M−1) and 2,6Me-β-CD (770 M−1). Thus, we propose that both formulations (2HP-β-CD:quercetin, 2,6Me-β-CD:quercetin) could be further explored and exploited as small molecule carriers in biological studies.

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