Metronidazole release using natural rubber latex as matrix

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Estudos de adsorção de tetraciclina em partículas de quitosana

Due to its physico-chemical and biological properties, related to the abundance and low cost of raw material, chitosan has been recognized as a material of wide application in various fields, such as in drug delivery systems. Many of these properties are associated with the presence of amino groups in its polymer chain. A proper determination of these amino groups is very important, in order to properly specify if a given chitosan sample can be used in a particular application. Thus, in this work, initially, a comparison between the determination of the deacetylation degree by conductometry and elemental analysis was carried out using a detailed analysis of error propagation. It was shown that the conductometric analysis resulted in a simple and safe method for the determining the degree of deacetylation of chitosan. Subsequently, experiments were performed to monitor and characterize the adsorption of tetracycline on chitosan particles through kinetic and equilibrium studies. The main models of kinetics and adsorption isotherms, widely used to describe the adsorption on wastewater treatment systems and the drug loading, were used to treat the experimental data. Firstly, it was shown that an apparent linear t/q(t) × t relationship did not imply in a pseudo-second-order adsorption kinetics, differently of what has been repeatedly reported in the literature. It was found that this misinterpretation can be avoided by using non-linear regression. Finally, the adsorption of tetracycline on chitosan particles was analyzed using insights obtained from theoretical analysis, and the parameters generated were used to analyze the kinetics of adsorption, the isotherm of adsorption and to ropose a mechanism of adsorption

Obtenção de sistemas microemulsionados e estudo de simulação por dinâmica molecular de sistemas micelares objetivando a veiculação de produtos naturais bioativos

Among the new drugs launched into the market since 1980, up to 30% of them belong to the class of natural products or they have semisynthetic origin. Between 40-70% of the new chemical entities (or lead compounds) possess poor water solubility, which may impair their commercial use. An alternative for administration of poorly water-soluble drugs is their vehiculation into drug delivery systems like micelles, microemulsions, nanoparticles, liposomes, and cyclodextrin systems. In this work, microemulsion-based drug delivery systems were obtained using pharmaceutically acceptable components: a mixture Tween 80 and Span 20 in ratio 3:1 as surfactant, isopropyl mirystate or oleic acid as oil, bidistilled water, and ethanol, in some formulations, as cosurfactants. Self-Microemulsifying Drug Delivery Systems (SMEDDS) were also obtained using propylene glycol or sorbitol as cosurfactant. All formulations were characterized for rheological behavior, droplet size and electrical conductivity. The bioactive natural product trans-dehydrocrotonin, as well some extracts and fractions from Croton cajucara Benth (Euphorbiaceae), Anacardium occidentale L. (Anacardiaceae) e Phyllanthus amarus Schum. & Thonn. (Euphorbiaceae) specimens, were satisfactorily solubilized into microemulsions formulations. Meanwhile, two other natural products from Croton cajucara, trans-crotonin and acetyl aleuritolic acid, showed poor solubility in these formulations. The evaluation of the antioxidant capacity, by DPPH method, of plant extracts loaded into microemulsions evidenced the antioxidant activity of Phyllanthus amarus and Anacardium occidentale extracts. For Phyllanthus amarus extract, the use of microemulsions duplicated its antioxidant efficiency. A hydroalcoholic extract from Croton cajucara incorporated into a SMEDDS formulation showed bacteriostatic activity against colonies of Bacillus cereus and Escherichia coli bacteria. Additionally, Molecular Dynamics simulations were performed using micellar systems, for drug delivery systems, containing sugar-based surfactants, N-dodecylamino-1-deoxylactitol and N-dodecyl-D-lactosylamine. The computational simulations indicated that micellization process for N-dodecylamino-1- deoxylactitol is more favorable than N-dodecyl-D-lactosylamine system.

Encapsulação de nanopartículas de magnetita em matriz de poli(metacrilato de metilacoácido metacrílico) por processo de polimerização em miniemulsão

Magnetic particles are systems with potential use in drug delivery systems, ferrofluids, and effluent treatment. In many situations, such as in biomedical applications, it is necessary to cover magnetic particles with an organic material, as polymers. In this work, magnetic particles were obtained through covering magnetite particles with poly(methyl methacrylate‐comethacrylic acid) via miniemulsion polymerization process. The resultant materials were characterized X‐ray diffraction (XRD), Fourier Transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), zeta potential (��) measurements and vibrating sample magnetometry (VSM). XRD results showed magnetite as the predominant cristalline phase in all samples and that cristallites had nanometric dimensions. Thermogravimetric analysis revealed an increase in polymer thermal stability as a result of magnetite encapsulation. TGA results showed also that the encapsulation efficiency was directly related to nanoparticles s hidrofobicity degree. VSM measurements showed that magnetic polymeric particles were superparamagnetic, so that they may be potentially used for magnetic (bio)separation

Gastrointestinal transit and disintegration of enteric coated magnetic tablets assessed by ac biosusceptometry

The oral administration is a common route in the drug therapy and the solid pharmaceutical forms are widely used. Although much about the performance of these formulations can be learned from in vitro studies using conventional methods, evaluation in vivo is essential in product development. The knowledge of the gastrointestinal transit and how the physiological variables can interfere with the disintegration and drug absorption is a prerequisite for development of dosage forms. The aim of this work was to employing the ac biosusceptometry (ACB) to monitoring magnetic tablets in the human gastrointestinal tract and to obtain the magnetic images of the disintegration process in the colonic region. The ac biosusceptometry showed accuracy in the quantification of the gastric residence time, the intestinal transit time and the disintegration time (DT) of the magnetic formulations in the human gastrointestinal tract. Moreover, ac biosusceptometry is a non-invasive technique, radiation-free and harmless to the volunteers, as well as an important research tool in the pharmaceutical, pharmacological and physiological investigations. (c) 2005 Elsevier B.V. All rights reserved.

Enteric coated magnetic HPMC capsules evaluated in human gastrointestinal tract by AC biosusceptometry

Purpose. To employ the AC Biosusceptometry (ACB) technique to evaluate in vitro and in vivo characteristics of enteric coated magnetic hydroxypropyl methylcellulose (HPMC) capsules and to image the disintegration process.Materials and Methods. HPMC capsules filled with ferrite (MnFe2O4) and coated with Eudragit (R) were evaluated using USP XXII method and administered to fasted volunteers. Single and multisensor ACB systems were used to characterize the gastrointestinal (GI) motility and to determine gastric residence time (GRT), small intestinal transit time (SITT) and orocaecal transit time (OCTT). Mean disintegration time (t (50)) was quantified from 50% increase of pixels in the imaging area.Results. In vitro and in vivo performance of the magnetic HPMC capsules as well as the disintegration process were monitored using ACB systems. The mean disintegration time (t (50)) calculated for in vitro was 25 +/- 5 min and for in vivo was 13 +/- 5 min. In vivo also were determined mean values for GRT (55 +/- 19 min), SITT (185 +/- 82 min) and OCTT (240 +/- 88 min).Conclusions. AC Biosusceptometry is a non-invasive technique originally proposed to monitoring pharmaceutical dosage forms orally administered and to image the disintegration process.

Desenvolvimento de sistema magnético polimérico contendo antimicrobianos para tratamento de infecções por Helicobacter pylori

Helicobacter pylori is the main cause of gastritis, gastroduodenal ulcer disease and gastric cancer. The most recommended treatment for eradication of this bacteria often leads to side effects and patient poor compliance, which induce treatment failure. Magnetic drug targeting is a very efficient method that overcomes these drawbacks through association of the drug with a magnetic compound. Such approach may allow such systems to be placed slowed down to a specific target area by an external magnetic field. This work reports a study of the synthesis and characterization of polymeric magnetic particles loaded with the currently used antimicrobial agents for the treatment of Helicobacter pylori infections, aiming the production of magnetic drug delivery system by oral route. Optical microscopy, scanning electron microscopy, transmission electron microscopy, x-ray powder diffraction, nitrogen adsorption/desorption isotherms and vibrating sample magnetometry revealed that the magnetite particles, produced by the co-precipitation method, consisted of a large number of aggregated nanometer-size crystallites (about 6 nm), creating superparamagnetic micrometer with high magnetic susceptibility particles with an average diameter of 6.8 ± 0.2 μm. Also, the polymeric magnetic particles produced by spray drying had a core-shell structure based on magnetite microparticles, amoxicillin and clarithromycin and coated with Eudragit® S100. The system presented an average diameter of 14.2 ± 0.2 μm. The amount of magnetite present in the system may be tailored by suitably controlling the suspension used to feed the spray dryer. In the present work it was 2.9% (w/w). The magnetic system produced may prove to be very promising for eradication of Helicobacter pylori infections

AC Biosusceptometry Technique to Evaluate the Gastrointestinal Transit of Pellets under Influence of Prandial State

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

The controlled release of antibiotic by hydroxyapatite: Anionic collagen composites

Major problems with the treatment of osteomyelitis are associated with poor antibiotic distribution at the site of infection due to limited blood circulation to the skeletal tissue. Improved treatment procedures have been used in drug delivery systems that include bioceramics and natural and synthetic polymers. This work reports the development of anionic collagen:hydroxyapatite composite paste for sustained antibiotic release. Antibiotic release by the composite was characterized by two steps. In the first, 15.0 +/- 4.9% was released in the first 5 h (n = 53) by a normal Fick diffusion mechanism. In the second step, only 16.8 +/- 2.2% was released after 7 days. In conclusion, hydroxyapatite:anionic collagen composite can be an efficient support for sustained antibiotic release in the treatment of osteomyelitis because most of the antibiotic release may be associated with composite bioresorption, thus permitting antibiotic release throughout the healing process. Hydroxyapatite:anionic collagen paste showed good biocompatibility associated with bone tissue growth with material still being observed after 60 days from the time of implants.

Disintegration of magnetic tablets in human stomach evaluated by alternate current Biosusceptometry

Oral administration is the most convenient route for drug therapy. The knowledge of the gastrointestinal transit and specific site for drug delivery is a prerequisite for development of dosage forms. The aim of this work was to demonstrate that is possible to monitor the disintegration process of film-coated magnetic tablets by multi-sensor alternate current Biosusceptometry (ACB) in vivo and in vitro. This method is based on the recording of signals produced by the magnetic tablet using a seven sensors array and signal-processing techniques. The disintegration was confirmed by signals analysis in healthy human volunteers' measurements and in vitro experiments. Results showed that ACB is efficient to characterize the disintegration of dosage forms in the stomach, being a research tool for the development of new pharmaceutical dosage forms. (C) 2003 Elsevier B.V. All rights reserved.

Biomagnetic Methods: Technologies Applied to Pharmaceutical Research

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Vírus da leucemia felina: análise da classificação da infecção, das técnicas de diagnóstico e da eficácia da vacinação com o emprego de técnicas sensíveis de detecção viral

O Vírus da leucemia felina (FeLV) pertence à família Retroviridae, gênero Gammaretrovirus. Diferentemente de outras retroviroses, uma parcela dos gatos jovens e adultos exposta ao FeLV não apresenta antigenemia/viremia, de acordo com as técnicas convencionais de detecção viral, como isolamento em cultivo celular, imunofluorescência direta e ELISA. O emprego de técnicas de maior sensibilidade para detecção e quantificação viral, como o PCR quantitativo, permitiu a identificação de animais positivos para a presença de DNA proviral e RNA na ausência de antigenemia/viremia e, com isso, um refinamento da análise das diferentes evoluções da infecção. Assim, reclassificou-se a patogenia do FeLV em 4 categorias: infecção abortiva, regressiva, latente e progressiva. Foi possível também detectar DNA proviral e RNA em animais considerados imunes ao FeLV após vacinação. Diante disso, os objetivos desta revisão de literatura foram demonstrar as implicações da utilização de técnicas sensíveis de detecção viral na interpretação e classificação da infecção do FeLV e rever as técnicas de detecção do vírus para fins de diagnóstico. Além disso, apresentar os resultados referentes à eficácia da vacinação contra o FeLV com a utilização dessas técnicas.

Synthesis and Characterization of Novel, Highly Crystalline Poly(vinyl alcohol) Microspheres for Chemoembolization Therapy

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Doxorubicin biocompatible O/W microemulsion stabilized by mixed surfactant containing soya phosphatidylcholine

Microemulsions (ME) containing soya phosphatidylcholine (SPC/polyoxyethylenglycerol trihydroxystearate 40 (EU)/sodium oleate (SO) as surfactant cholesterol (CHO) as oil phase and aqueous buffer were studied. Pseudo-ternary phase diagrams of the investigated systems were obtained at constant SPC/EU/SO weight ratio 3.5:3.5:3.0 by titration, in order to characterize the proportions between the components to form clear systems. The dynamic light scattering results showed that the size of the oil droplets decreases significantly with the ratio of surfactant/oil phase added to system. Depending on the composition ME system could exhibit a thixotropic behavior. The apparent viscosity increased 25- and 13-folds with cholesterol concentration for drug-free and drug-load ME, respectively. It was also verified that the octanol/aqueous buffer partition coefficient (K-O/B) of doxorubicin (DOX) was pH dependent increasing abruptly above pH 6.0. It was possible to incorporate 2.24 mg/ml of DOX into ME. The incorporation of DOX in the ME systems increased the droplets size for all surfactant concentrations used in the system. The results suggest that DOX interacts with the microstructure of the ME at the studied pH increasing significantly the drug solubility. It was possible to conclude that the investigated ME can be a very promising vehicle as drug-carrier for administration of doxorubicin. (c) 2006 Elsevier B.V. All rights reserved.

Relationship between structural features and in vitro release of doxorubicin from biocompatible anionic microemulsion

In this work structural features of anionic microemulsions, containing the pharmaceutical biocompatible components soya phosphatidylcholine (SPC), eumulgin HRE 40 (EU) and sodium oleate (SO) as surfactant, cholesterol (CHO) as oil phase and aqueous buffer were studied. Microemulsions were formulated with and without the antitumor drug doxorubicin (DOX). The various microstructures characterized in the pseudo-temary phase diagram were analyzed by polarized light microscopy, small-angle X-ray scattering (SAXS) and X-ray diffraction (XRD) as well as by their ability to incorporate and release DOX. The experimental results demonstrated a correlation between the composition, the structural features and drug delivery. It was found that at higher cholesterol contents, the crystallization of CHO polymorph phases changed the mobility of DOX molecules. Droplets were formed with short-range spatial correlation from a microemulsion (ME) with a low surfactant:oil ratio. More ordered structures with lamellar arrangements formed by the increasing of the CHO proportions in the formulation may be due to CHO crystallization. The in vitro release of DOX showed that the presence of a high content of crystalline CHO prolongs the release of DOX from ME. The retention of DOX in the internal oil phase of the ME may modulate the drug release for a prolonged time. These results clearly demonstrate the potential of ME as a drug-delivery system. (c) 2007 Elsevier B.V. All rights reserved.