Design of Dosage Forms with Improved Biopharmaceutical Properties.

The development of a pharmaceutical product consists of giving a drug an optimal dosage form (a certain state of aggregation, consistency, structural, mechanical, physicochemical, and functional properties), which ensure stability, the possibility of accurate dosage, the required pharmacological effect, and ease of administration with minimal side effects [...

β-Cyclodextrin Modified Hydrogels of Kappa-Carrageenan for Methotrexate Delivery.

This work is aimed at developing a kappa-carrageenan (kCR) gel with increased methotrexate (MTX) content. β-Cyclodextrin (βCD), which is able to inclusion complex formation with MTX, has been used to increase the drug concentration in the hydrogel. The rheological behavior of the designed gels was investigated and the influence of MTX and βCD on the viscoelastic properties of kCR gel was studied in detail.

Regularities of Encapsulation of Tolfenamic Acid and Some Other Non-Steroidal Anti-Inflammatory Drugs in Metal-Organic Framework Based on γ-Cyclodextrin.

Metal-organic frameworks based on cyclodextrins (CDs) have been proposed as promising drug delivery systems due to their large surface area, variable pore size, and biocompatibility. In the current work, we investigated an incorporation of tolfenamic acid (TA), a representative of non-steroidal anti-inflammatory drugs (NSAIDs), in a metal-organic framework based on γ-cyclodextrin and potassium cations (γCD-MOF). Composites γCD-MOF/TA obtained by absorption and co-crystallization methods were characterized using powder X-ray diffraction, low temperature nitrogen adsorption/desorption, scanning electron microscopy, and FTIR spectroscopy.

Entropy Effects in Intermolecular Associations of Crown-Ethers and Cyclodextrins with Amino Acids in Aqueous and in Non-Aqueous Media.

The analysis of the ratios of entropy and enthalpy characteristics and their contributions to the change in the Gibbs energy of intermolecular interactions of crown ethers and cyclodextrins with amino acids is carried out. Two different types of macrocycles were chosen for examination: crown ethers with a hydrophilic interior and cyclodextrins with a hydrophobic inner cavity and a hydrophilic exterior. The thermodynamics of complex formation of crown ethers and cyclodextrins with amino acids in water and aqueous-organic solvents of variable composition was examined.

Improvement of pharmacologically relevant properties of methotrexate by solid dispersion with Pluronic F127.

Solid dispersion with Pluronic F127 was proposed as alternative approach to modify the pharmacologically relevant properties of methotrexate (MTX). Solid dispersion of MTX with Pluronic F127 was prepared by fusion method and characterized by powder X-ray diffraction, thermal analysis, scanning electron microscopy and FTIR spectroscopy with the aim to elucidate the physical state of the dispersed MTX and the nature of the interactions occurring between MTX and the carrier. Effect of Pluronic F127 on solubility, dissolution rate, membrane permeability, and pharmacokinetic parameters was revealed in vitro and in vivo.

Selective Binding of Cyclodextrins with Leflunomide and Its Pharmacologically Active Metabolite Teriflunomide.

The selectivity of encapsulation of leflunomide and teriflunomide by native α-, β- and γ-cyclodextrins was investigated through H NMR and molecular modeling. Thermodynamic analysis revealed the main driving forces involved in the binding. For α-cyclodextrin, the partial encapsulation was obtained while deep penetration was characterized for the other two cyclodextrins, where the remaining polar fragment of the molecule is located outside the macrocyclic cavity.

Methotrexate-loaded metal-organic frameworks on the basis of γ-cyclodextrin: Design, characterization, in vitro and in vivo investigation.

In this work, metal-organic frameworks on the basis of γ-cyclodextrin (γCD-MOF) were proposed as carriers for methotrexate (MTX) which is widely used as chemotherapy agent and immune system suppressant. The synthesized γCD-MOF was loaded with MTX by impregnation and co-crystallization. The obtained composites were characterized using powder X-ray diffraction, N adsorption/desorption, FTIR spectroscopy, solid-state C MAS CP/TOSS NMR and scanning electron microscopy.

γ-Cyclodextrin-metal organic frameworks as efficient microcontainers for encapsulation of leflunomide and acceleration of its transformation into teriflunomide.

γ-Cyclodextrin-based metal-organic framework (γCD-MOF) crystals were successfully synthesized using a vapor diffusion method. An applicability of γCD-MOF for encapsulation of immunosuppressive disease-modifying antirheumatic drug leflunomide (LEF) was examined. Loading of LEF in γCD-MOF was performed by impregnation and co-crystallization.

Improved Biopharmaceutical Properties of Oral Formulations of 1,2,4-Thiadiazole Derivative with Cyclodextrins: in Vitro and in Vivo Evaluation.

The synthesized 1,2,4-thiadiazole derivative displaying biological activity has low aqueous solubility and dissolution rate. Novel oral formulations of thiadiazole with β- and hydroxypropyl-β-cyclodextrins were obtained by grinding and freeze-drying methods with the purpose to improve the aqueous solubility. Complex formation of 1,2,4-thiadiazole derivative with cyclodextrins was confirmed by means of solid-state C MAS CP/TOSS NMR.

Effects of Biorelevant Media Components on Dissolution Behaviour of 1,2,4-Thiadiazole Derivative Designed for Alzheimer's Disease Prevention.

In this study, dissolution behaviour of 1,2,4-thiadiazole derivative (1-[5-(3-chloro-phenylamino)-1,2,4-thiadiazol-3-yl]-propan-2-ol) displaying an anti-Alzheimer activity was examined in biorelevant media such as Simulated Gastric Fluid (SGF, pH 1.2), Fasted State Simulated Gastric Fluid (FaSSGF, pH 1.6) and Fasted State Simulated Intestinal Fluid (FaSSIF, pH 6.

Cocrystal formation, crystal structure, solubility and permeability studies for novel 1,2,4-thiadiazole derivative as a potent neuroprotector.

The cocrystallization approach has been applied to modify the poor solubility profile of the biologically active 1,2,4-thiadiazole derivative (TDZ). Extensive cocrystal screening with a library of coformers resulted in formation of a new solid form of TDZ with vanillic acid in a 1:1 molar ratio. The cocrystalline phase was identified and characterized by thermal and diffraction analyses including single-crystal X-ray diffraction.

Thermostability of photosystem I trimers and monomers from the cyanobacterium Thermosynechococcus elongatus.

The performance of solar energy conversion into alternative energy sources in artificial systems highly depends on the thermostability of photosystem I (PSI) complexes Terasaki et al. (2007), Iwuchukwu et al. (2010), Kothe et al.

Towards the rational design of novel drugs based on solubility, partitioning/distribution, biomimetic permeability and biological activity exemplified by 1,2,4-thiadiazole derivatives.

Novel 1,2,4-thiadiazole derivatives as potent neuroprotectors were synthesized and identified. Their ability to inhibit the glutamate stimulated Ca uptake was investigated. The solubility of thiadiazoles was measured in a buffer solution (pH 7.

Red chlorophyll excitation dynamics in Arthrospira platensis photosystem I trimeric complexes as studied by femtosecond transient absorption spectroscopy.

Femtosecond absorption spectroscopy was applied to study for the first time excitation dynamics in isolated photosystem I trimers from Arthrospira platensis, which display extremely long-wavelength absorption peaks. Pump-probe spectra observed at 77K in the timescale of dozens of picoseconds upon 70-fs excitation revealed two maxima near 710 and 730 nm, which correspond to red chlorophyll forms. Bleaching at 680 nm developed in ∼ 200 fs, whereas the bleaching kinetics at 710 and 730 nm exhibited two components with time constants of 1 and 5.

Cyclodextrin-benzoic acid binding in salt solutions: effects of biologically relevant anions.

Inclusion complex formation of benzoic acid with α-, β- and γ-cyclodextrins in water and in 0.2 M solutions of inorganic salts (KCl, KBr, KH2PO4 and K2SO4) has been studied by means of 1H NMR at 298.15 K.

Long-wavelength chlorophylls in photosystem I of cyanobacteria: origin, localization, and functions.

The structural organization of photosystem I (PSI) complexes in cyanobacteria and the origin of the PSI antenna long-wavelength chlorophylls and their role in energy migration, charge separation, and dissipation of excess absorbed energy are discussed. The PSI complex in cyanobacterial membranes is organized preferentially as a trimer with the core antenna enriched with long-wavelength chlorophylls. The contents of long-wavelength chlorophylls and their spectral characteristics in PSI trimers and monomers are species-specific.

α-Cyclodextrin/aminobenzoic acid binding in salt solutions at different pH: dependence on guest structure.

Influence of Na(+) and K(+) cations on α-cyclodextrin guest-host complex formation with isomeric aminobenzoic acids was examined at different pH and temperature of 298.15 K by (1)H NMR and calorimetry methods. More pronounced influence of Na(+) on inclusion complex formation of α-CD with aminobenzoic acid anions compare to the effects of Na(+) on α-CD complex formation with zwitterionic aminobenzoic acid molecules was revealed.

Selective Na(+)/K(+) effects on the formation of α-cyclodextrin complexes with aromatic carboxylic acids: competition for the guest.

We investigated the effects of K(+) and Na(+) ions on the formation of α-cyclodextrin complexes with ionized aromatic carboxylic acids. Using solution calorimetry and (1)H NMR, we performed the thermodynamic and structural investigation of α-cyclodextrin complex formation with benzoic and nicotinic acids in different aqueous solutions containing K(+) and Na(+) ions as well as in pure water. The experiments show that the addition of sodium ions to solution leads to a decrease in the binding constants of the carboxylic acids with α-cyclodextrin as compared to pure water and solutions containing potassium ions.

[Variability of light-induced circular dichroism spectra of photosystem I complexes of cyanobacteria].

Circular dichroism (CD) spectra of photosystem I (PSI) complexes of the cyanobacteria Thermosynechococcus elongatus, Arthrospira platensis and Synechocystis sp. PCC 6803 were studied. CD spectra of dark-adapted PSI trimers and monomers, measured at 77 K, show common bands at 669-670(+), 673(+), 680(-), 683-685(-), 696-697(-), 702(-) and 711(-) nm.

Investigation of the pH-dependent complex formation between beta-cyclodextrin and dipeptide enantiomers by capillary electrophoresis and calorimetry.

The effect of pH on complex formation between beta-CD and the enantiomers of the dipeptides Ala-Phe, Ala-Tyr and Asp-PheOMe was investigated at 298.15 K by CE and calorimetry. Beta-CD displayed a higher enantioselectivity toward the protonated peptides compared to their zwitterionic forms.

Calorimetric and X-ray studies of clathrate hydrates of tetraisoamylammonium polyacrylates.

The structure of clathrate hydrates with tetraisoamylammonium polyacrylate salt incorporated as guest has been studied in this work. Also, quantitative studies on the stability changes of the clathrate hydrates with different degrees of cross-linking of the guest polymer (varied from 0 to 3%) have been conducted. A single crystal X-ray diffraction study of a crystal of the hydrate with linear (uncross-linked) tetraisoamylammonium polyacrylate as guest reveals a hexagonal structure (space group P6m2, a = 12.

Quantum yield of P700+ photodestruction in isolated photosystem I complexes of the cyanobacterium Arthrospira platensis.

The photostability of P700 cation radical (P700+) was studied by evaluating the quantum yields of P700(+) photodestruction in photosystem I (PSI) complexes of the cyanobacterium Arthrospira platensis. The time courses of P700+ photodestruction in PSI trimers and monomers have been measured in aerobic conditions under selective excitation of far-red absorption band of P700+ by intense light of laser diodes. Long-term exposure of PSI complexes to 808 or 870 nm laser light caused destruction of P700+ and antenna chlorophylls.

Interactions of beta- and hydroxypropyl-beta-cyclodextrin with some purine alkaloids: thermodynamic study.

The effect of native and hydroxypropylated beta-cyclodextrin on the solubility and activity of some purine alkaloids was examined. For this purpose, the solubility of purine alkaloids in pure water and in aqueous solutions of mentioned beta-cyclodextrins was determined at 298.15 K.

Effects of oxygen and photosynthesis carbon cycle reactions on kinetics of P700 redox transients in cyanobacterium Arthrospira platensis cells.

Effects of oxygen and photosynthesis and respiration inhibitors on the electron transport in photosystem I (PSI) of the cyanobacterium Arthrospira platensis cells were studied. Redox transients of P700 were induced by illumination at 730 nm and monitored as kinetics of the absorption changes at 810 nm; to block electron influx from PSII, the measurements were performed in the presence of 30 microM 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU). Inhibitors of terminal oxidases (potassium cyanide and pentachlorophenol) insignificantly influenced the fast oxidation of P700 under aerobic conditions, whereas removal of oxygen significantly decelerated the accumulation of P700(+).