Amine bridges grafted mesoporous silica, as a prolonged/controlled drug release system for the enhanced therapeutic effect of short life drugs.

Hybrid mesoporous silica SBA-15, with surface incorporated cross-linked long hydrophobic organic bridges was synthesized using stepwise synthesis. The synthesized materials were characterized by elemental analysis, infrared spectroscopy, nuclear magnetic resonance spectroscopy, nitrogen adsorption, X-rays diffraction, thermogravimetry and scanning and transmission electron microscopy. The functionalized material showed highly ordered mesoporous network with a surface area of 629.0m2g-1. The incorporation of long hydrophobic amine chains on silica surface resulted in high drug loading capacity (21% Mass/Mass) and prolonged release of ibuprofen up till 75.5h. The preliminary investigations suggests that the synthesized materials could be proposed as controlled release devices to prolong the therapeutic effect of short life drugs such as ibuprofen to increase its efficacy and to reduce frequent dosage.

Preparation and characterization of glycidyl methacrylate organo bridges grafted mesoporous silica SBA-15 as ibuprofen and mesalamine carrier for controlled release.

Mesoporous silica SBA-15 was synthesized and functionalized with bridged polysilsesquioxane monomers obtained by the reaction of 3-aminopropyltriethoxy silane with glycidyl methacrylate in 2:1 ratio. The synthesized mesoporous silica materials were characterized by elemental analysis, infrared spectroscopy, nuclear magnetic resonance spectroscopy, nitrogen adsorption, X-ray diffraction, thermogravimetry and scanning electron microscopy. The nuclear magnetic resonance in the solid state is in agreement with the sequence of carbon distributed in the attached organic chains, as expected for organically functionalized mesoporous silica. After functionalization with organic bridges the BET surface area was reduced from 1311.80 to 494.2m(2)g(-1) and pore volume was reduced from 1.98 to 0.89cm(3)g(-1), when compared to original precursor silica. Modification of the silica surface with organic bridges resulted in high loading capacity and controlled release of ibuprofen and mesalamine in biological fluids. The Korsmeyer-Peppas model better fits the release data indicating Fickian diffusion and zero order kinetics for synthesized mesoporous silica. The drug release rate from the modified silica was slow in simulated gastric fluid, (pH1.2) where less than 10% of mesalamine and ibuprofen were released in initial 8h, while comparatively high release rates were observed in simulated intestinal (pH6.8) and simulated body fluids (pH7.2). The preferential release of mesalamine at intestinal pH suggests that the modified silica could be a simple, efficient, inexpensive and convenient carrier for colon targeted drugs, such a mesalamine and also as a controlled drug release system.

The applicability of ordered mesoporous SBA-15 and its hydrophobic glutaraldehyde-bridge derivative to improve ibuprofen-loading in releasing system.

The mesoporous SBA-15 silica with uniform hexagonal pore, narrow pore size distribution and tuneable pore diameter was organofunctionalized with glutaraldehyde-bridged silylating agent. The precursor and its derivative silicas were ibuprofen-loaded for controlled delivery in simulated biological fluids. The synthesized silicas were characterized by elemental analysis, infrared spectroscopy, (13)C and (29)Si solid state NMR spectroscopy, nitrogen adsorption, X-ray diffractometry, thermogravimetry and scanning electron microscopy. Surface functionalization with amine containing bridged hydrophobic structure resulted in significantly decreased surface area from 802.4 to 63.0 m(2) g(-1) and pore diameter 8.0-6.0 nm, which ultimately increased the drug-loading capacity from 18.0% up to 28.3% and a very slow release rate of ibuprofen over the period of 72.5h. The in vitro drug release demonstrated that SBA-15 presented the fastest release from 25% to 27% and SBA-15GA gave near 10% of drug release in all fluids during 72.5 h. The Korsmeyer-Peppas model better fits the release data with the Fickian diffusion mechanism and zero order kinetics for synthesized mesoporous silicas. Both pore sizes and hydrophobicity influenced the rate of the release process, indicating that the chemically modified silica can be suggested to design formulation of slow and constant release over a defined period, to avoid repeated administration.

Free amino and imino-bridged centres attached to organic chains bonded to structurally ordered silica for dye removal from aqueous solution.

Ordered mesoporous SBA-15 type silica was synthesized by sol gel polymerization and reacted with 3-aminopropyltriethoxysilane (AP) or triethylenetetramine (TE), to attach pendant chains or bridging molecules, with basic centres. The materials were characterized by elemental analysis, infrared spectroscopy, and nuclear magnetic resonance in the solid state, X-ray diffractometry, scanning and transmission electron microscopy. The nitrogen sorption/desorption data for SBA-15 and the organofunctionalized SBA-15AP and SBA-15TE silicas resulted in IV type isotherms with hysteresis loops of the H1 type, surface areas of 800; 213 and 457 m(2) g(-1) and average pore diameters of 8.0; 3.2 and 6.8 nm, respectively. The ordered structural features of the mesoporous silica remained preserved after post-functionalization with pendant and bridged organic chains. Sorption data for organofunctionalized silicas gave highly selective sorption capacities for anionic water soluble Reactive Blue dye, with 0.064 and 0.072 mmol g(-1). Negligible sorption was observed with the unmodified mesoporous silica. The results suggest that organofunctionalized silica can be a simple, efficient, inexpensive and suitable method for the effective and selective removal of anionic organic dye pollutants from aqueous solutions.

L-tryptophan transport through a hydrophobic liquid membrane using AOT micelles: dynamics of the process as revealed by small angle X-ray scattering.

Hydrophobic liquid membranes have a high technological potential in many fields of separation science. The dynamics of these systems is very complex and still not fully understood. In this work we studied the effect of the incorporation of cationic and anionic L-tryptophan at pH 1.8 and 10.0, respectively, in Aerosol-OT reverse micelles performing small angle X-ray scattering experiments. The use of a synchrotron radiation source allowed efficient in situ data acquisition. Several insights on L-tryptophan transport dynamics through hydrophobic membranes containing AOT could be obtained from these SAXS experiments, such as amino acid site localization and changes in the reverse micelle sizes.

An investigation of chlorophenol proton affinities and their influence on the biological activity of microorganisms.

The proton affinities of 15 chlorophenols are calculated by ab initio methods. Straight correlation between proton affinities and changes in the electronic structure is observed. The proton affinities decrease linearly with the electronic density gain on the chlorine atoms, as the liberation of the proton increases. To confirm the importance of the proton affinities on the toxicity of chlorophenols, calorimetric responses of these molecules and related ones where the acid proton is changed to a methyl group (anisol and its chlorinated derivatives) were used to verify their effects on Chromobacterium violaceum. The results confirmed that the chlorophenols are more toxic than the respective chloroanisols and suggest that high proton affinities are associated with low toxic activity. The toxicity of the chlorophenols can be associated with the respiratory mechanism in some microorganisms.

The use of violacein to study biochemical behaviour of Saccharomyces cerevisiae cells.

Violacein, a biochemical compound produced by Chromobacterium violaceum which has antichagasic properties, was used to study biochemical behaviour of Saccharomyces cerevisiae cells. At 20 microM and 40 microM, violacein did not alter the membrane potential (deltapsi) of S. cerevisae cells, which means that the integrity of the cell membrane was maintained. On the other hand, at 60 microM and 80 microM, violacein produced significant alterations in the membrane potential. This information will be very useful in using S. cerevisiae cells as a model to test the toxicity of new drugs before using in animals or human beings.

Flow microcalorimetric studies of phenol and its chlorinated derivatives and a theoretical evaluation of their possible inhibition mode on Chromobacterium violaceum respiration.

The general belief that chemical structure determines the biological effect of drugs has led to several techniques to establish structure-activity relationships (SAR) that is useful in the development of more active compounds. Predicting toxic effects based on SAR, one can obtain toxicological data with a low cost-benefit ratio. Chlorophenols that represent a class of toxic agents frequently used in industrial processes are not satisfactorily described in the literature in relation to their toxicity. The main objective of this work is to relate the microbial activities of phenol, anisole and their chlorinated derivatives on Chromobacterium violaceum respiration with their physicochemical properties. Anisole and its chlorinated derivatives were used to evaluate the influence of phenol acidity on biological activity. The calculations were carried out at the semi-empirical AM1 and ab initio DFT levels employing the basis sets CEP-31G, CEP-31+Ge CEP-31G** that were parameterized using the continuum-solvation model COSMO for solvent contribution. Both empirical and theoretical properties were evaluated by chemometric analyses (hierarchical cluster analysis (HCA) and principal component analysis (PCA)), to correlate the physicochemical properties of the phenol, anisole and their chlorinated derivatives with their biological activities. The results obtained for the current work indicate that the biological activities of these compounds increase as the n-octanol/water (logP) partition coefficients, ionization energies (IP), melting points (mp) and dissociation constants increase and the solvent effects (SE), enthalpies of formation (DeltafH degrees ) and proton affinities (PA) decrease.