Use of Materials Based on Polymeric Silica as Bone-Targeted Drug Delivery Systems for Metronidazole.

Mesostructured ordered silica-based materials are the promising candidates for local drug delivery systems in bone disease due to their uniform pore size and distribution, and high surface area which affect their excellent adsorption properties, good biocompatibility and bioactivity, and versatile functionalization so that their properties can be controlled. Ordered mesoporous silica (MCM-41 type) was synthesized by a surfactant-assisted sol-gel process using tetraethoxysilane as a silica precursor and hexadecyltrimethylammonium bromide as the structure-directing agent. Functionalized silica materials containing various types of organic groups (3-aminopropyl, 3-mercaptopropyl, or 3-glycidyloxypropyl groups) were synthesized by the post-grafting method onto pre-made mesoporous silica. Comparative studies of their structural characteristics, the surface mineralization activity and release properties for the model drug Metronidazole (MT) were then conducted. It has been found that porosity parameters, mineralization activity and adsorption/release of metronidazole from mesoporous channels of silica can be regulated using functional groups which are chemically bounded with an outer silica surface. The preferential mineral nucleation was found on negatively charged surfaces-MCM-41, and mercaptopropyl and glycidyloxypropyl functionalized silica (MCM-SH and MCM-epoxy, respectively) in simulated body fluid (SBF solution), as well as a sustained release of MT. In contrast to them, aminopropyl-functionalized samples (MCM-NH2) achieved a high MT release rate. These results confirm the potential of silica-based materials for local therapeutic applications (as drug carriers and bone substitutes) in bone disease.

Formulation and In Vitro Characterization of Bioactive Mesoporous Silica with Doxorubicin and Metronidazole Intended for Bone Treatment and Regeneration.

The purpose of this study was to evaluate the surface mineralization activity and in vitro drug behavior potential of two forms of mesoporous silica: powder and granulate. Ordered mesoporous SiO2 powder was synthesized by surfactant-assisted sol-gel process using tetraethoxysilane as a silica precursor and hexadecyltrimethylammonium bromide as the structure-directing agent. The granulate was prepared using silica powder and ethyl cellulose as a binding agent. Metronidazole (MT)-an anti-inflammatory substance and doxorubicin hydrochloride (ChD)-an anti-cancer drug were chosen as drug models for delivery studies. The results of structural characteristic studies, utilizing transmission electron microscope (TEM) and scanning electron microscope (SEM) images, powder X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and nitrogen adsorption-desorption (BET) measurements, show that obtained materials have two-dimensional hexagonal p6mm symmetry, high specific surface area, narrow pore size, and a satisfactory mineralization behavior in the simulated body solution (SBF, pH = 7.4). The release rate of drugs depends upon the structural features of the drug molecules and the form of the carrier material. Of both the drugs analyzed, faster release was observed for small MT molecules characterized by weaker interactions with the carrier. In addition, the slower drug release was observed with granulate form due to increased diffusion barrier for drugs. Obtained results prove that the MT/ChD-loaded silica formulations could be attractive materials for filling bone defects and for local delivery systems.

Preparation and in vitro characterisation of bioactive mesoporous silica microparticles for drug delivery applications.

The aim of this study was to evaluate the surface mineralization activity and in vitro drug behaviour potential of new mesoporous silica microparticles (MSM). The unmodified MSM (MSM-0%Ca) and calcium-modified MSM (MSM-5%Ca, MSM-15%Ca, MSM-25%Ca) were prepared using the self-assembling method. Calcium diethoxide was used as a calcium precursor. Doxorubicin hydrochloride (DOX), used as an anticancer model drug, was selected to the drug loading and release studies. The DOX loading into the microparticles was performed by liquid adsorption process. The self-formation of carbonate hydroxyapatite (C-Hap) on the MSM surface was examined under in vitro biomimetic conditions. The samples were characterised by means of scanning-transmission electron microscopy (STEM) and energy dispersive X-ray spectrometry, powder X-ray diffraction, Fourier transform infrared spectroscopy, and nitrogen adsorption-desorption measurements. The results indicated an inverse relationship--while increasing the total amount of calcium in the MSM composition the surface area and pore volume decrease with a simultaneous increase in the pore size. This was correlated with a progressive increase in the surface mineralization ability--especially its initial promotion, and in the decrease in MSM drug loading efficiency. The release rate of the DOX can be effectively tailored by varying the amount of calcium, where the elution rate of DOX increases with an increasing amount of the Ca precursor.

The Design of Nanostructured Metronidazole-Loaded HPC/Oxide Xerogel Composites: Influence of the Formulation Parameters on In Vitro Characterisation.

In this study, oxide and polymer/oxide xerogels with metronidazole were prepared and examined as carriers of drug for the local application to the bone. The nanoporous SiO2-CaO-P2O5 and HPC-SiO2-CaO-P2O5 xerogel materials with different amounts of the polymer [hydroxypropyl cellulose (HPC)] were prepared using the sol-gel technology, and their physicochemical properties were characterised with respect to chemical structure [by Fourier transform infrared spectroscopy (FTIR)], porosity and the specific surface area of solids (BET), crystallinity [by X-ray powder diffraction (XRD)], morphology [by scanning electron microscope (SEM)] and the in vitro release of the metronidazole over time (by UV-vis spectroscopy, in the ultraviolet light region). HPC-modified oxide xerogels as the carriers of drug showed slower release of metronidazole, due to the structure and stronger interactions with drug as compared with the pure oxide xerogel. Kinetic analysis indicated diffusional mechanism of drug release from all xerogel carriers. HPC addition to the oxide material resulted in a decrease in the porosity and improved the bioactive properties of xerogels. Obtained results for xerogel composites suggest that the metronidazole-loaded xerogels could be attractive candidates for local delivery systems particularly to a bone.

The Role of Polydimethylsiloxane in the Molecular Structure of Silica Xerogels Intended for Drug Carriers.

The aim of this study was to prepare and examine polymer/oxide xerogels with metronidazole (MT) as delivery systems for the local application of a drug to a bone. The nanoporous SiO2-CaO and PDMS-modified SiO2-CaO xerogel materials with different amounts of the polymer, polydimethylsiloxane (PDMS), were prepared by the sol-gel method. Characterization assays comprised the analysis of the composite materials by using Fourier transform infrared spectroscopy (FTIR), determining the specific surface area of solids (BET), using X-ray powder diffraction (XRD) and scanning electron microscope (SEM) techniques, and further monitoring in the ultraviolet and visible light regions (UV-Vis) of the in vitro release of the drug (metronidazole) over time. According to these results, the bioactive character and chemical stability of PDMS-modified silica xerogels have been proven. The release of MT from xerogels was strongly correlated with the composition of the matrix. In comparison with the pure oxide matrix, PDMS-modified matrices accelerated the release of the drug through its bigger pores, and additionally, on account of weaker interactions with the drug. The obtained results for the xerogel composites suggest that the metronidazole-loaded xerogels could be promising candidates for formulations in local delivery systems particularly to bone.

Influence of surfactants on the release behaviour and structural properties of sol-gel derived silica xerogels embedded with metronidazole.

The aim of this study was to obtain stable and controlled release silica xerogels containing metronidazole (MT) prepared with surfactants with different charges: cetyltrimethylammonium bromide (CTAB), sodium dodecyl sulphate (SDS) and hydroxypropyl cellulose (HPC), which could be the promising carrier materials used as the implantable drug delivery systems. The xerogels were prepared by the sol-gel method. The influence of various formulation precursors on porosity parameters and drug release were investigated. Addition of surfactants showed a promising result in controlling the MT release. Dissolution study revealed increased release of MT from silica modified SDS and CTAB, whereas the release of MT from silica modified HPC considerably decreased, in comparison with unmodified silica. The addition of surfactants showed slight changes in porosity parameters. All xerogels are characterized by a highly developed surface area (701-642 m(2) g(-1)) and mesoporous structure. The correlation between pore size obtained matrices and release rate of drug was also observed. Based on the presented results of this study, it may be stated that applied xerogel matrices: pure silica and surfactants-modified silica could be promising candidates for the formulation in local delivery systems.

The sol-gel prepared SiO2-CaO-P2O5 composites doped with Metronidazole for application in local delivery systems.

The aim of this study was to evaluate the physical properties, chemical structure and bioactivity of sol-gel processed oxide (SiO(2)-CaO-P(2)O(5)) composites used as controlled release materials for Metronidazole-drug applied in periodontal disease treatment. The obtained composite materials were characterized by Fourier transform infrared spectroscopy (FTIR), X-ray powder diffraction (XRD), the Brunauer-Emmet-Teller (BET) technique and further monitoring in the ultraviolet and visible light regions (UV-Vis) of the in vitro release of the drug over time. Using tetramethoxysilane (TMOS) as a precursor of silica matrix and calcium nitrate tetrahydrate (Ca(NO(3))(2) 4H(2)O), triethyl phosphite (P(OC(2)H(5))(3)) as precursors of CaO and P(2)O(5) respectively, xerogels with different morphology and physical properties were obtained. The applied modifications improved also the bioactivity and changed the profile of the drug release. Based on the presented results of this study, it may be concluded that applied xerogel matrices could be promising candidates for the formulation in local delivery systems.

Sol-gel processed porous silica carriers for the controlled release of diclofenac diethylamine.

Silica xerogels doped with diclofenac diethylamine were prepared by the sol-gel method from a hydrolysed tetraethoxysilane (TEOS) solution containing diclofenac diethylamine. Two different catalysts, drying conditions and levels of water content were used to alter the microstructure of the silica xerogels. The aim of this study was to determine the rate of Diclofenac release from the silica xerogels. This in vitro study showed that the sol-gel method is useful for entrapping Diclofenac in the pores of xerogels. It also showed that, in vitro, Diclofenac is released from the silica xerogel, through the pores, by diffusion. Base-catalysed gels proved to be much more effective than acid-catalyzed gels.

In vitro release of cisplatin from sol-gel processed organically modified silica xerogels.

SiO2, SiO2/PEG and SiO2/PDMS xerogels were examined as polymeric carriers for the controlled release of cisplatin--an antineoplasmic medicine. Drug/carrier systems were prepared by the sol-gel method. The effect of organic substitution of the silica xerogel matrix and drying conditions on the release of cisplatin was evaluated. Based on the presented results of the study it may be stated that sol-gel method is useful for entrapping a cisplatin in the pores of organically modified silica gels and for releasing cisplatin mainly in the way of diffusion from the pores of the lattice under the in vitro conditions. The use of organic impurities in silica gel increased the release of cisplatin from xerogel (from 62% to 97% within 7 days), and thermal treatment of all xerogels with cisplatin at the temperature of 80 degrees C resulted in the acceleration of the drug release (2 days) and increase of the released drug (89-98%).

The effect of PEG concentration on the release rate of cisplatin from PEG-modified silica xerogels.

Cisplatin-an antineoplastic medicine-was incorporated into a polyethylene glycol (PEG)-modified silica xerogels received by the sol-gel method. The influence of PEG concentration and drying temperature on the release of cisplatin was studied. From our results we may state that addition of PEG (MW 600) and drying of silica xerogels at 80 degrees C augmented the release of cisplatin. The release of cisplatin from the matrices grows with the increase of PEG volume in xerogel (up to 74-97% within 7 days), whereas application of thermal drying resulted in both increased speed and amount of the drug released up to 91-97% within 2 days.

[Selenium concentration in serum of women with thyroid gland disease]. / Stezenie selenu w surowicy krwi u kobiet ze schorzeniami tarczycy.

The aim of this study was to estimate the concentration of total selenium in serum women with thyroid gland disease. Selenium was determined by atomic absorption spectrometry using the hydride generation technique (HG-AAS). Selenium was determined in 30 patients with thyroid gland disease and in 12 healthy controls. Selenium concentration of serum was variously in patients than in control group and patients with different thyroid gland disease. The average concentration of selenium in control group was 0.0694 microg/ml, in goiter group 0.0529 microg/ml, in hyperactivity group 0.0441 microg/ml, in hypofunction group 0.0520 microg/ml.g/ml.

[Evaluation of the usefulness of spectrophotometric method based on the reaction of formation of silic-molybdenum blue for determination of silica in hydrogenated fat]. / Ocena przydatnosci metody kolorymetrycznej opartej na reakcji tworzenia blekitu krzemomolibdenowego do oznaczania krzemionki w tluszczach utwardzanych.

The spectrophotometric method based on the reaction of formation of silic-molybdenum blue for determination of silica (silicon dioxide) in hydrogenated fat was developed. Determination limit of silica in this method was 15.6 mg/kg and average recovery 77.77%. Using this method the content of silica in the edible fat (margarine) taken from the market was determined. The samples of margarine before determination of silicon dioxide were mineralised and than the analyte was concentrated. The silica was not found in the margarine samples at levels above the determination limit of spectrophotometric method i.e. 15.6 mg/kg.

Evaluation of optical changes of three types of lenses: hard PMMA, hydrogel, and heparin surface modified hard lenses effected by silicone oil, used clinically as a substitute of the vitreous body.

The objective of these investigations was an in vitro evaluation whether silicone oil OXANE of viscosity 5700 cSt clinically used in eye surgery as a substitute of the vitreous body, being in contact with an artificial polymer lens used as an implant of human lens, causes the changes in its optical properties. The paper presents the results of spectral analysis of transmission of visible (VIS) radiation of three types of artificial lenses: hard PMMA, hydrogel, heparin surface modified (HSM) hard PMMA, and the same lenses damaged by YAG laser radiation with an energy increasing from 1.7 mJ to 3.7 mJ, exposed to clinically applied silicone oil. The studies were carried out, in two-week intervals, over a period of 20 weeks. Hard PMMA and HSM lenses were found not to have changed their optical properties after 20 weeks of exposure to silicone oil. The measured transmittance values were within the range of instrumental error (+/- 1%). Optical properties of hydrogel lenses exposed to silicone oils deteriorated with exposure and after 20-week exposure to silicone oil the average transmittance value decreased by about 18%, reaching its final value of 67.08 +/- 2.37% (RSD = 5.56%). A minimal decrease of the initial transmittance values was observed only for the lenses exposed to laser radiation of highest energy (3.7 mJ). After completed exposure to silicone oil, two kinds of lenses were found to have a slightly improved transmittance: hard PMMA lenses by about 4% and HSM lenses by about 2%. On the other hand, in case of hydrogel lenses the deterioration of optical properties to the extent comparable to that of hydrogel lenses not damaged by laser radiation was observed.