Papers by Author: T. López

Abstract: Current epilepsy rates in Mexico are 4% (SERSAME-Health Ministry), of which 80% correspond to Temporal Lobe Epilepsy (TLE). Antiepileptic drug administration is systemic, meaning that 90% of the active agent is lost between administration and delivery to the epileptic focus in the brain. Severe toxic secondary effects may occur as a result. The present study is aimed at developing an alternative antiepileptic drug delivery system. In this study, a sol-gel nanostructured titania device, in which valproic acid (VPA) has been encapsulated. This is a nanoparticulate device, which is biocompatible with brain tissue. Stereotactic surgery was used to implant the reservoirs in the temporal lobe of Wistar rats, using chemical kindling, which was used to induce epilepsy. The reservoir was designed to release the drug at a constant rate over a period of at least one year. A functional study was performed on the efficiency of drug delivery in order to evaluate the effect on spontaneous and induced neuron electrical activity. A new discovery, which is presented here, shows that in the case of damaged brain tissue, as is the case in epilepsy, the accumulation of red globules, oxygen transportation results in the formation of calcium carbonate crystals which surround the epileptic focus. Because these crystals have a specific polarization, we propose to characterize their influence on the EEG using statistical methods. The electrical activity was measured by electroencephalography using 5 healthy rats without and 5 rats with an implanted VPA/device. Cerebral signals describe the complex behavior of the brain dynamics as a function of time. Fractal algorithms are sensitive to fluctuations and lead to the analysis and characterization of this kind of complex phenomena. A systematic study of these EEG’s was made in order to observe the variation of signals during seizures and on the controlled rate of release of VPA. We have estimated the Hurst exponent (H) to measure long range-dependence. Preliminary results show that for the control group, signal behavior is persistent (H>0.5), while for the epileptic group antipersistency was observed (H<0.5), with variations due seizure stages. During the protection period using VPA, preliminary results show that values tend to reach original behavior, as the crisis is stabilized.

Abstract: Sol-gel nanostructured titania (TiO2) was functionalized in order to produce a nanomaterial biocompatible with brain tissue. Neuroreservoirs made from titania microtubes have been used to release sodium phenytoin and valproic acid. In vitro and in vivo probes were used to treat the epilepsy disease. Pore space topology and interactions between matrix and drug are the most important phenomena that affect the drug diffusion and liberation kinetics. Accordingly, fractal morphology of nanostructured titania as a function of pH and polarity of the drug added during the gelation reactions was studied. The transmission electronic microscopy (TEM), scanning electronic microscopy (SEM), and N2 adsorption (BET) were employed to characterize the nanomaterials with maximum amount of air hollows occluded inside a drug. It was found that the clusters and pores in nanostructured titania are characterized by the universal fractal dimensions and . However, the characteristic sizes of particles and pores, the porosity, and the fractal dimension of pore surface ( ) are dependent on hydrolysis water concentration added during the gelation reaction. So, the matrix hydroxylation permits to control the drug liberation kinetics.

Abstract: Mesoporous silica type SBA-15 has high specific surface area, well ordered pores and renders larges volumes, reasons for its potential use in controlled drug delivery system; in addition its non toxic nature and good biocompatibility. The aim of this work is to determine the feasibility of loading collagen-polyvinylpyrrolidone (collagen-PVP) molecules into Biocompatible Nanostructured Ordered Mesoporous Silica (BINOM-Silica). Collagen-PVP has several medical uses, such as fibrolytic activity and tissue regeneration. Therefore, this BINOM-Silica/collagen- PVP material could be used as drug delivery system for hypertrophic scarring. Different BINOMSilica materials were prepared using a triblock copolymer in an acid medium and stabilized at 557°C and later, collagen-PVP was loaded into the material. The small angle powder X-ray diffraction patterns of BINOM-Silica materials, in some cases, indicate the existence of a high degree of hexagonal mesoscopic organization. The nitrogen sorption isotherms are type IV typical of mesoporous materials with large surface area. In vitro release of collagen-PVP was carried out by mean of UV/VIS spectroscopy. The cumulative release profiles of Silica-collagen PVP in distilled water indicate a two step release, an initial fast release and a relatively slow subsequent release, indicating an appropriate delivery of collagen-PVP for therapeutic administration. BINOMSilica/ collagen-PVP intradermical administration stimulated inflammatory infiltrates only in an acute phase (day 3), demonstrating that silica materials and their combination with chemical and biological drugs could be safe for therapeutics. The absence of inflammatory infiltrates at day 7 suggested an appropriate integration of BINOM-Silica/collagen-PVP into the tissue. These results indicate that we obtained biocompatible nanostructured ordered mesoporous silica materials useful for delivery systems.