Characterization of sodium phenytoin co-gelled with titania for a controlled drug-release system
Introduction
The administration of medicaments by a drug delivery system provides a number of advantages over conventional therapies [1], [2], [3], [4], [5]. The brain is a fragile organ and the therapies to control cerebral disorders are complicated. Many existing pharmaceuticals are rendered ineffective in its treatment due to the inability to effectively deliver and maintain them inside the nervous tissue. The major problem in attempting to deliver a drug into the brain, is the presence of the blood–brain barrier (BBB) which constraints drug penetration, even in certain pathological situations when the BBB is partly disrupted. Despite successful examples of drug delivery to the Central Nervous System (SNC) by using nanoparticles of silica, coated particles with polymer films, etc. [6], [7], [8], [9], [10], searching for a less invasive treatment to deliver therapeutic substances into the brain has proved to be cumbersome. The large investment in research and development in rational drug design for controlled drug delivery into the brain is of great interest to the pharmaceutical industry [11]. Recently, investigations are also driving the need for new effective drug delivery methods. Various strategies have been proposed to improve the delivery of drugs to the nervous tissue using nano-scale materials. Additional benefits of using targeted nano-scale drug carriers are: reduced drug toxicity and more efficient drug distribution. Several nano-scale structures such as solid spheres, hollow spheres, tubes, porous particles, solid particles, and branched structures can be designed. To achieve such nanostructures, different manufacturing methods have been used depending on the type of material. A sol–gel method enables the production of nanoparticles with homogeneous drug distribution, and allows synthesizing drug reservoirs at ambient temperature, necessary for handling and to maintain the chemical structure of the drug intact.
The delivery of a drug through a nano-structured material has the potential to enhance drug bio-agility, improve the time release, and enable precise drug targeting. The complete drug dose needed for a given period of time can be incorporated in the nanoreservoir and implanted at once in the patient, releasing the drug in a controlled manner in the site of interest, in this case, the brain. Formation of an inorganic oxide matrix at ambient temperature favors the encapsulation of the drug, leading to the production of a reservoir with the active ingredient homogenously distributed throughout the resulting gel (or xerogel). Moreover, the physical characteristics (including density, pore size, and nanostructure) of the oxides produced by sol–gel processing can be tailored by controlling the sol–gel reaction kinetics, and in particular, the relative rates of hydrolysis and condensation. The ability to control the gel microstructure has important implications for the design of controlled-release systems using sol–gel chemistry [12], [13], [14], [15].
The aim of this study was to stabilize sodium phenytoin in a titania sol–gel inorganic matrix. The sample morphology was characterized by transmission electron microscopy (TEM) and scanning electron microscopy (SEM). The structural studies were made by Fourier transform infrared spectroscopy (FT-IR) and X-ray diffraction (XRD). Finally the porosity was measured by nitrogen adsorption using the BET equation.
Section snippets
Sample preparation
A mixture of sodium phenytoin (Ph), ethanol and water was put in a reflux reactor system at 30 °C with constant stirring. After 30 min of reaction, titanium n-butoxide was added to the solution drop-wise. Finally, alcohol was eliminated using low vacuum, and the titania drug reservoirs were dried at 30 °C for 1 week. The concentration of sodium phenytoin was 50, 100, 200 and 250 mg per 20 g of sol–gel titania, i.e. molar ratios were: alkoxide/water = 1/8 and alkoxide/alcohol = 1/16.
Morphological analysis
The particle
Morphological analysis
SEM and TEM were used to analyze pure TiO2 and titania–Ph-X samples to identify morphological changes. The SEM images of pure sol–gel titania observed at two different magnification (Fig. 1a and b) show the formation of spherical agglomerates with different sizes ranging from 0.1 up to 0.8 μm. Moreover, transmission micrographs (dark and bright field) were performed in order to detect individual nanoparticles (Fig. 1c and d). When phenytoin is co-gelled with sol–gel titania, the increment of
Conclusions
Morphological studies show homogeneous agglomerates formed by nanoparticles between 10 and 30 nm. From FT-IR studies it can be concluded that the chemical structure of sodium phenytoin remains unchanged when it is co-gelled with titania. X-ray diffraction showed that all the samples were amorphous. The meso-porous reservoirs showed a higher surface area compared with pure titania. Therefore, a higher drug concentration can be anchored at the surface of the gel. The use of a nano-device sol–gel
Acknowledgements
The authors wish to thank A. Estrella and R. Perera for technical assistance. This work was partially supported by CONACYT No. 38490-E, UAM-Iztapalapa and also by CyTED.
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