Katarzyna Czarnobaj

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.

Preparation and Characterization of Silica Xerogels as Carriers for Drugs

The aim of the present study was to utilize the sol-gel method to synthesize different forms of xerogel matrices for drugs and to investigate how the synthesis conditions and solubility of drugs influence the change of the profile of drug release and the structure of the matrices. Silica xerogels doped with drugs were prepared by the sol-gel method from a hydrolyzed tetraethoxysilane (TEOS) solution containing two model compounds: diclofenac diethylamine, (DD)—a water-soluble drug or ibuprofen, (IB)—a water insoluble drug. Two procedures were used for the synthesis of sol-gel derived materials: one-step procedure (the sol-gel reaction was carried out under acidic or basic conditions) and the two-step procedure (first, hydrolysis of TEOS was carried out under acidic conditions, and then condensation of silanol groups was carried out under basic conditions) in order to obtain samples with altered microstructures. In vitro release studies of drugs revealed a similar release profile in two steps: an initial diffusion-controlled release followed by a slower release rate. In all the cases studied, the released amount of DD was higher and the released time was shorter compared with IB for the same type of matrices. The released amount of drugs from two-step prepared xerogels was always lower than that from one-step base-catalyzed xerogels. One-step acid-catalyzed xerogels proved unsuitable as the carriers for the examined drugs.

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.

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 °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.

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 (SiO2-CaO-P2O5) 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(NO3)2 4H2O), triethyl phosphite (P(OC2H5)3) as precursors of CaO and P2O5 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.

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 m2 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 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.