FORMATION OF BURST CHEMILUMINESCENCE, EXCITED ALDEHYDES, AND SINGLET OXYGEN IN MODEL REACTIONS AND FROM CARCINOGENIC COMPOUNDS IN RAT LIVER S9 FRACTIONS

It is shown that in physiological circumstances (T=298 K, pH=7.4) various aldehydes (formaldehyde, acetaldehyde, glyoxal, methyl-glyoxal, etc.) can be activated by hydrogen peroxide (H202) in the presence of the ε-amino group of L-lysine, with simultaneous formation of singlet oxygen (1O2 ) and chemiluminescence. The activated aldehydes are in an excited state and have radical structure causing extremely high reactivity and a possible attack of cellular components like proteins, amino acids, RNA and DNA. In the reactions methylated, formylated, acetylated, etc. compounds are formed as well. Activated aldehydes can also be formed during the biological oxidation of different nitrosamines (DMN, DEN, N-nitroso-morpholine) and formaldehyde-hydrazine adduct. It is proved that in rat liver S9 fractions these activated (excited) aldehydes, especially formaldehyde, have been formed with a simultaneous burst chemiluminescence emission and appearance of singlet oxygen. In rat liver S9 fractions excited formaldehyde can be liberated only after 30 min preincubation time from dimethyl-nitrosamine (DMN) and monomethyl-hydrazine (MMH). On the other hand, excited formaldehyde is liberated immediately from hydrazine-formaldehyde-adduct (HZ/FORM) and isonicotinic acid-hydrazide-formaldehyde adduct (INH/FORM), i.e. no preincubation is necessary

Role of Cytotoxicity Experiments in Pharmaceutical Development

Through the twentieth century, the road from synthetizing a new drug molecule to become an actual product got longer than ever before. Cytotoxicity assays are a quick way to assess a certain chemical compound’s effects on a given human cell line. The most well-known techniques are the MTT- and the LDH-assays. These tests are cheap, easy to execute, but not very precise and dependent on various environmental factors and also, they show no detail about the time-dependency of the toxic effect. Cytotoxicity experiments are a crucial part of a modern pharmaceutical development process. They are a cheap and safe way to get vital information about a new molecule’s biological attributes focusing on its basic tolerability. These studies not only save human lives and test animals, but they save the time and resources to be spared on a test molecule which is a complete failure having no in vitro safety

Cyclodextrins in Drug Delivery Systems and Their Effects on Biological Barriers

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Preformulation studies and bioavailability enhancement of curcumin with a ‘two in one’ PEG-β-cyclodextrin polymer

Drug delivery systems are used to improve the biopharmaceutical properties of curcumin. Our aim was to investigate the effect of a water-soluble ‘two in one’ polymer containing covalently bonded PEG and βCD moieties (βCPCD) on the solubility and bioavailability of curcumin and compare it to a polymeric β-cyclodextrin (βCDP) cross-linked with epichlorohydrin. Phase-solubility and dynamic light scattering (DLS) experiments showed that the solubility of curcumin increased significantly in 10 m/m % βCPCD and βCDP solutions, but βCPCD–curcumin particles had higher hydrodynamic volume. The formation of the βCPCD–curcumin complex in solution and sedimented phase was confirmed by NMR spectroscopy. Biocompatibility and permeability experiments were performed on Caco-2 cells. Polymers did not show cytotoxicity up to 10 m/m % and βCPCD significantly increased the permeability of curcumin. DLS measurements revealed that among the interaction of polymers with mucin, βCPCD formed bigger aggregates compared to βCDP. Curcumin complexes were lyophilized into capsules and structurally characterized by micro-CT spectroscopy. Drug release was tested in a pH 1.2 medium. Lyophilized complexes had a solid porous matrix and both βCPCD and βCDP showed rapid drug release. βCPCD provides an opportunity to create a swellable, mucoadhesive matrix system for oral drug delivery

Protective Effect of Pure Sour Cherry Anthocyanin Extract on Cytokine-Induced Inflammatory Caco-2 Monolayers

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Pharmacokinetic Properties of Fluorescently Labelled Hydroxypropyl-Beta-Cyclodextrin

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