This study aimed to obtain and characterize an RU-β-CD complex in the context of investigating the possibility of changes in the solubility, stability, antioxidative and microbiological activity as well as permeability of complexated rutin as against its free form. The formation of the RU-β-CD complex via a co-grinding technique was confirmed by using DSC, SEM, FT-IR and Raman spectroscopy, and its geometry was assessed through molecular modeling. It was found that the stability and solubility of the so-obtained complex were greater compared to the free form; however, a slight decrease was observed inits antibacterial potency. An examination of changes in the EPR spectra of thecomplex excluded any reducing effect of complexation on the antioxidative activity of rutin. Considering the prospect of preformulation studies involving RU-β-CD complexes, of significance is also the observed possibility of prolongedly releasing rutin from the complex at a constant level over along period of 20 h, and the fact that twice as much complexated rutin was able topermeate compared to its free form.

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Graphene oxide (GO) was modified by two modified porphyrins (THPP and TCPP) to form GO–porphyrin hybrids. Spectroscopic measurements demonstrated the formation of stable supramolecular aggregates when mixing two components in solution. The Fourier transform infrared (FTIR) and Raman scattering measurements confirm π-stacking between hydrophobic regions of GO nanoflakes and porphyrin molecules. On the number and the kind of paramagnetic centers generated in pristine GO samples, which originate from spin anomalies at the edges of aromatic domains within GO nanoflakes. More significant changes in electronic properties have been observed in hybrid materials. This is particularly evident in the drastic increase in the number of unpaired electrons for the THPP-GO sample and the decrease in the number of unpaired electrons for the TCPP-GO. The difference of paramagnetic properties of hybrid materials is a consequence of π-stacking between GO and porphyrin rings. An interesting interplay between modifiers and the surface of GO leads to a significant change in electronic structure and magnetic properties of the designed hybrid materials. Based on the selection of molecular counterpart we can affect the behavior of hybrids upon light irradiation in a different manner, which may be useful for the applications in photovoltaics, optoelectronics, and spintronics.

A novel approach for drug design based on the oral carbapenem analog tebipenem pivoxil (TP) has been proposed. The formation of the tebipenem pivoxil-β-cyclodextrin (TP-β-CD) complex resulted in changes concerning physicochemical properties of TP, which is significant for planning the development of an innovative pharmaceutical formulation as well as in the modifications of biological activity profile of the studied delivery system. The inclusion of TP into β-cyclodextrin (β-CD) was confirmed by spectral (infrared and Raman spectroscopies) and thermal method (differential scanning calorimetry). Precise indications of TP domains responsible for interaction with β-CD were possible through a theoretical approach. The most important physicochemical modifications obtained as an effect of TP inclusion were changes in solubility and its rate depending on acceptor fluids, and an increase in chemical stability in the solid state. Biologically essential effects of TP and β-CD interactions were decreased TP permeability through Caco–2 cell monolayers with the use of efflux effect inhibition and increased antibacterial activity. The proposed approach is an opportunity for development of the treatment in resistant bacterial infections, in which along with physicochemical modifications induced by a drug carrier impact, a carrier synergy with a pharmacological potential of an active pharmaceutical substance could be used.

This study aimed to investigate changes in the solubility and antimicrobial efficacy of cefuroxime axetil (CA) when incorporated into cyclodextrin (CD). While choosing the CD, the validated in silico model was used. A theoretical model based on docking and molecular mechanics/generalized born surface area was validated using a curated dataset of API (active pharmaceutical ingredient)–CD stability constants. The library of commonly used cyclodextrins was virtually screened, indicating CA –hydroxypropyl-βCD (HPβCD) as the most thermodynamically favored system. Solid-state CA–HPβCD system was prepared and characterized by differential scanning calorimetry (DSC), Fourier-transform infrared (FT-IR), and X-ray diffraction (XRPD) methods. The dissolution profiles of the CA and its cyclodextrin system were evaluated. Microbiological activity of the CA–HPβCD inclusion system was studied based on changes in minimal inhibitory concentration (MIC) values and related to ones of the pure CA. The theoretical model was successfully validated, obtaining an average correlation with experimental data R = 0.7. The dissolution study showed significantly improved dissolution profiles of CA–HPβCD compared to CA. HPβCD increases the antimicrobial efficacy of CA up to 4-fold compared to pure CA.

The large amount of data that has been collected so far for G protein-coupled receptors requires machine learning (ML) approaches to fully exploit its potential. Our previous ML model based on gradient boosting used for prediction of drug affinity and selectivity for a receptor subtype was compared with explicit information on ligand-receptor interactions from induced-fit docking. Both methods have proved their usefulness in drug response predictions. Yet, their successful combination still requires allosteric/orthosteric assignment of ligands from datasets. Our ligand datasets included activities of two members of the secretin receptor family: GCGR and GLP-1R. Simultaneous activation of two or three receptors of this family by dual or triple agonists is not a typical kind of information included in compound databases. A precise allosteric/orthosteric ligand assignment requires a continuous update based on new structural and biological data. This data incompleteness remains the main obstacle for current ML methods applied to class B GPCR drug discovery. Even so, for these two class B receptors, our ligand-based ML model demonstrated high accuracy (5-fold cross-validation Q2 > 0.63 and Q2 > 0.67 for GLP-1R and GCGR, respectively). In addition, we performed a ligand annotation using recent cryogenic-electron microscopy (cryo-EM) and X-ray crystallographic data on small-molecule complexes of GCGR and GLP-1R. As a result, we assigned GLP-1R and GCGR actives deposited in ChEMBL to four small-molecule binding sites occupied by positive and negative allosteric modulators and a full agonist. Annotated compounds were added to our recently released repository of GPCR data.

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The study focused on the pharmacological action of sumatriptan, in particular its antiallodynic and antihyperalgesic properties, as an effect of cyclodextrinic inclusion of sumatriptan, resulting in changes of its physicochemical qualities such as dissolution and permeability through artificial biological membranes, which had previously been examined in vitro in a gastro-intestinal model. The inclusion of sumatriptan into β-cyclodextrin and 2-hydroxylpropylo-β-cyclodextrin by kneading was confirmed with the use of spectral (fourier-transform infrared spectroscopy (FT-IR); solid state nuclear magnetic resonance spectroscopy with magic angle spinning condition, 1H and 13C MAS NMR) and thermal (differential scanning calorimetry (DSC)) methods. A precise indication of the domains of sumatriptan responsible for its interaction with cyclodextrin cavities was possible due to a theoretical approach to the analysis of experimental spectra. A high-performance liquid chromatography with a diode-array detector method (HPLC-DAD) was employed to determine changes in the concentration of sumatriptan during dissolution and permeability experiments. The inclusion of sumatriptan in complex with cyclodextrins was found to significantly modify its dissolution profiles by increasing the concentration of sumatriptan in complexed form in an acceptor solution compared to in its free form. Following complexation, sumatriptan manifested an enhanced ability to permeate through artificial biological membranes in a gastro-intestinal model for both cyclodextrins at all pH values. As a consequence of the greater permeability of sumatriptan and its increased dissolution from the complexes, an improved pharmacological response was observed when cyclodextrin complexes were applied.