Effects of ultraviolet radiation on 3,4-benzpyrene and other polycyclic aromatic hydrocarbons; carcinogenic activity of aqueous extracts from irradiated 3,4-benzpyrene.
It was shown in preceding papers (2, 3) that when 3,4-benzpyrene dissolved in benzene was irradiated with monochromatic radiation of wave length 2,537 A. in the presence of oxygen, at least two water-soluble substances were included in the products and that these could be recognized, and some of their properties deduced, by spectrophotometric methods. The first, substance A, was characterized at pH 8 by an absorption band whose maximum intensity was at 3,600 A. It was labile, readily taking up atmospheric oxygen irreversibly when its aqueous solutions were allowed to stand at room temperature; but it could be stabilized by cooling them to 0 ~ C. and storing them in an atmosphere of nitrogen. The second substance, B, absorbed at 2,760 A. and was more stable to oxygen, but it was destroyed by strong alkali. It reacted readily with glutathione and with other compounds containing sulfhydryl groups. Water-soluble oxidation products of 3,4-benzpyrene are of course well known. A monohydroxy derivative is excreted as a metabolite when the hydrocarbon is fed to rats (8, 13); and a photoderivative has been described that has the power to inhibit respiratory enzymes (6, 7). None of them, however, has been reported to have any carcinogenic activity. Rideal and Schulman have shown (12) that materials very similar to, if not identical with, substances ,4 and B are readily adsorbed onto protein monolayers, and so might be expected to pass more readily than the unadsorbed hydrocarbon through cell membranes. By analogy with hemolytic substances, which they showed to possess this property to a high degree, substances ,4 and B might thus be expected to be biologically active. Other observations recorded in the literature, which were summarized in the introduction to Part I, seem to support this view. Since the absorption bands of ,4 and B do not accord with those of any derivative
Reactions with Monolayers and their Biological Analogies
THE film technique permits us not only to examine the progress of chemical and enzyme reactions in monolayers but also to investigate mixed films, for example, lipo proteins, and the effects of injecting various reactants beneath monolayers. It has been found1 that the reactions of monolayers of lipoids such as cholesterol with substances injected into the substrate are dependent both on the nature of the polar group and on that of the hydrocarbon ‘tail’ of the injected reactant. Similar conclusions can be drawn as to the extent of reaction with monolayers of proteins. The possibilities in this case are somewhat more complex, for the protein monolayer must be regarded as a triplex system, the extended polypeptide chains separating an upper hydrophobic layer from a lower hydrophilic one, the latter containing the polar groups of the side chains of the protein.
Rational Design, Synthesis and Evaluation of γ-CD-Containing Cross-Linked Polyvinyl Alcohol Hydrogel as a Prednisone Delivery Platform
This study describes the in-silico rational design, synthesis and evaluation of cross-linked polyvinyl alcohol hydrogels containing γ-cyclodextrin (γ-CDHSAs) as platforms for the sustained release of prednisone (PDN). Through in-silico studies using semi-empirical quantum mechanical calculations, the effectiveness of 20 dicarboxylic acids to generate a specific cross-linked hydrogel capable of supporting different amounts of γ-cyclodextrin (γ-CD) was evaluated. According to the interaction energies calculated with the in-silico studies, the hydrogel made from PVA cross-linked with succinic acids (SA) was shown to be the best candidate for containing γ-CD. Later, molecular dynamics simulation studies were performed in order to evaluate the intermolecular interactions between PDN and three cross-linked hydrogel formulations with different proportions of γ-CD (2.44%, 4.76% and 9.1%). These three cross-linked hydrogels were synthesized and characterized. The loading and the subsequent release of PDN from the hydrogels were investigated. The in-silico and experimental results showed that the interaction between PDN and γ-CDHSA was mainly produced with the γ-CDs linked to the hydrogels. Thus, the unique structures and properties of γ-CDHSA demonstrated an interesting multiphasic profile that could be utilized as a promising drug carrier for controlled, sustained and localized release of PDN.