In vivo study of light-driven naproxen release from gated mesoporous silica drug delivery system.

A drug delivery system based on mesoporous particles MCM-41 was post-synthetically modified by photo-sensitive ligand, methyl-(2E)-3-(4-(triethoxysilyl)-propoxyphenyl)-2-propenoate (CA) and the pores of MCM-41 particles were loaded with Naproxen sodium salt (NAP). The CA was used as a photoactive molecule that can undergo a reversible photo-dimerization by [2π + 2π] cycloaddition when irradiated with UV light of specific wavelengths. Thus, it has a function of gate-keeper that is responsible for opening/closing the pores and minimizing premature release of NAP. The physicochemical properties of the prepared system were studied by infrared spectroscopy (IR), nitrogen adsorption measurements, thermogravimetric analysis (TGA), scanning transmission electron microscopy (STEM) and energy dispersive X-ray spectroscopy (EDX). The mechanism of the opening/closing pores was confirmed by UV measurements. In vitro and in vivo drug release experiments and the concentration of released NAP was determined by UV spectroscopy and high-performance liquid chromatography (HPLC). In vivo drug release in the blood circulatory system of rats has demonstrated the effective photo-cleavage reaction of CA molecules after UV-light stimulation. The localization and morphological changes of the particles were studied in the blood and liver of rats at different time intervals. The particles in the blood have been shown to retain their original rod-like shape, and the particles in the liver have been hydrolysed, which has resulted in spherical shape with a reduced size.

Mesoporous Silica as a Drug Delivery System for Naproxen: Influence of Surface Functionalization.

In this work we describe the relationship between surface modification of hexagonally ordered mesoporous silica SBA-15 and loading/release characteristics of nonsteroidal anti-inflammatory drug (NSAID) naproxen. Mesoporous silica (MPS) was modified with 3-aminopropyl, phenyl and cyclohexyl groups by grafting method. Naproxen was adsorbed into pores of the prepared MPS from ethanol solution using a solvent evaporation method. The release of the drug was performed in buffer medium at pH 2 and physiological solution at pH 7.4. Parent MPSs as well as naproxen loaded MPSs were characterized using physicochemical techniques such as nitrogen adsorption/desorption, thermogravimetric analysis (TG), Zeta potential analysis, Fourier transform infrared spectroscopy (FT-IR), and elemental analysis. The amount of naproxen released from the MPSs into the medium was determined by high-performance liquid chromatography (HPLC). It was shown that the adsorption and desorption characteristics of naproxen are dependent on the pH of the solution and the surface functionalization of the host.

Doxorobicin as cargo in a redox-responsive drug delivery system capped with water dispersible ZnS nanoparticles.

In this work, we have prepared and investigated a redox-responsive drug delivery system (DDS) based on a porous carrier. Doxorubicin (DOX), a chemotherapy medication for treatment of different kinds of cancer, was used as a model drug in the study. DOX was loaded in ordered hexagonal mesoporous silica SBA-15, a nanoporous material with good biocompatibility, stability, large pore size and specific surface area (S BET = 908 m2 g-1, V P = 0.79 cm3 g-1, d = 5.9 nm) and easy surface modification. To prepare the redox-responsive system, cystamine derivative ligands, with redox active disulphide linkers were grafted onto the surface of SBA-15. To ensure no significant premature release of DOX from the porous system, thioglycolic acid modified ZnS nanoparticles (ZnS-COOH NPs) were used as pore capping agents. The grafted redox-responsive cystamine derivative ligand containing disulphide linkers was bonded by a peptide bond to the thioglycolic acid groups of ZnS-COOH NPs, capping the pores. Once the disulphide bond was cleaved, the ZnS-COOH NPs caps were released and pores were opened to deliver the DOX cargo. The dithiol bond was cleavable by redox active molecules such as dithiothreitol (DTT) or glutathione, the concentration of which in cancer cells is 4 times higher than in healthy cells. The redox release of DOX was studied in two different media, physiological saline solution with DTT and saline without DTT. The prepared DDS proved the concept of redox responsive release. All samples were characterised by powder X-ray diffraction (XRD), transition electron microscopy (TEM), nitrogen adsorption/desorption at 77 K, Fourier-transform infrared spectroscopy (FTIR), thermal analysis and zeta potential measurements. The presence of semiconducting ZnS nanoparticle caps on the pore openings was detected by magnetic measurements using SQUID magnetometry showing that such cargo systems could be monitored using magnetic measurements which opens up the possibilities of using such drug delivery systems as theranostic agents.

A Study of 5-Fluorouracil Desorption from Mesoporous Silica by RP-UHPLC.

In cancer treatment, the safe delivery of the drug to the target tissue is an important task. 5-fluorouracil (5-FU), the well-known anticancer drug, was encapsulated into the pores of unmodified mesoporous silica SBA-15, as well as silica modified with 3-aminopropyl and cyclohexyl groups. The drug release studies were performed in two different media, in a simulated gastric fluid (pH = 2) and in a simulated body fluid (pH = 7) by RP-UHPLC. The simple and rapid RP-UHPLC method for quantitative determination of 5-fluorouracil released from unmodified and modified mesoporous silica SBA-15 was established on ODS Hypersil C18 column (150 × 4.6 mm, 5 µm) eluted with mobile phase consisted of methanol: phosphate buffer in volume ratio of 3:97 (v/v). Separation was achieved by isocratic elution. The flow rate was kept at 1 mL/min, the injection volume was set at 20 µL and the column oven temperature was maintained at 25 °C. The effluent was monitored at 268 nm. This paper provides information about the quantitative determination of the released 5-FU from silica. It was found out that larger amount of the drug was released in neutral pH in comparison with the acidic medium. In addition, surface functionalisation of silica SBA-15 influences the release properties of the drug.

Lipid Peroxidation Process in Meat and Meat Products: A Comparison Study of Malondialdehyde Determination between Modified 2-Thiobarbituric Acid Spectrophotometric Method and Reverse-Phase High-Performance Liquid Chromatography.

The aim of this work was to compare the methods of malondialdehyde detection, as the main secondary product of the lipid peroxidation process, in meat and meat products. Malondialdehyde measurements were performed by two modified methods, the 2-thiobarbituric acid spectrophotometric method and the reverse-phase high-performance liquid chromatography in raw, mechanically-deboned chicken meat and in manufactured frankfurters. The malondialdehyde concentrations measured by the 2-thiobarbituric acid spectrophotometric method were found to be overestimated by more than 25% in raw meat and more than 27% in frankfurters in comparison to the results of reverse-phase high-performance liquid chromatography (p < 0.05). The achieved results showed that the presented modified reverse-phase high-performance liquid chromatography method was more applicable and more accurate for the quantification of malondialdehyde in samples of meat and meat products.

The Determination of Food Dyes in Vitamins by RP-HPLC.

Reversed-phase high performance liquid chromatography (RP-HPLC) for the determination of five synthetic food dyes (Quinoline Yellow E104, Sunset Yellow E110, Ponceau 4R E124, Tartrazine E102 and Carmine E120) in vitamins was used. The dyes were analyzed within 10 min using a column with stationary phase C 18 (250 mm × 4.6 mm, 5 µm) at 40 °C with isocratic elution, and the mobile phase contained acetonitrile and a mixture of CH3COONa:CH3OH (85:15, v/v) in a ratio of 10:90 (v/v) for yellow-colored capsules and 20:80 (v/v) for red-colored capsules, respectively. A diode-array detector was used to monitor the dyes between 190 and 800 nm. It was established that the analyzed samples contained synthetic dyes in a concentration range from 79.5 ± 0.01 µg/capsule of Ponceau 4R, E124 to 524 ± 0.01 µg/capsule of Tartrazine, E102. The obtained results were compared with existing acceptable daily intakes (ADIs) for individual dyes. This paper provides information about the content of dyes in samples of vitamins. This information is not generally available to consumers.