Nanotechnological delivery systems for the oral administration of active molecules: Polymeric microparticles and microemulsions applied to anti-inflammatory and anti-infectious drugs

This thesis was devoted to the development of innovative oral delivery systems for two different molecules. In the first part, microparticles (MPs) based on xylan and Eudragit® S- 100 were produced and used to encapsulate 5-aminosalicylic acid for colon delivery. Xylan was extracted from corn cobs and characterized in terms of its physicochemical, rheological and toxicological properties. The polymeric MPs were prepared by interfacial cross-linking polymerization and spray-drying and characterized for their morphology, mean size and distribution, thermal stability, crystallinity, entrapment efficiency and in vitro drug release. MPs with suitable physical characteristics and satisfactory yields were prepared by both methods, although the spray-dried systems showed higher thermal stability. In general, spraydried MPs would be preferable systems due to their thermal stability and absence of toxic agents used in their preparation. However, drug loading and release need to be optimized. In the second part of this thesis, oil-in-water microemulsions (O/W MEs) based on mediumchain triglycerides were formulated as drug carriers and solubility enhancers for amphotericin B (AmB). Phase diagrams were constructed using surfactant blends with hydrophiliclipophilic balance values between 9.7 and 14.4. The drug-free and drug-loaded MEs presented spherical non-aggregated droplets around 80 and 120 nm, respectively, and a low polydispersity index. The incorporation of AmB was high and depended on the volume fraction of the disperse phase. These MEs did not reduce the viability of J774.A1 macrophage-like cells for concentrations up to 25 μg/mL of AmB. Therefore, O/W MEs based on propylene glycol esters of caprylic acid may be considered as suitable delivery systems for AmB

Micropartículas poliméricas à base de xilana e Eudragit® S-100 contendo mesalazina visando à liberação cólon-específica

Colon-specific drug delivery systems have attracted increasing attention from the pharmaceutical industry due to their ability of treating intestinal bowel diseases (IBD), which represent a public health problem in several countries. In spite of being considered a quite effective molecule for the treatment of IBD, mesalazine (5-ASA) is rapidly absorbed in the upper gastrointestinal tract and its systemic absorption leads to risks of adverse effects. The aim of this work was to develop a microparticulate system based on xylan and Eudragit® S- 100 (ES100) for colon-specific delivery of 5-ASA and evaluate the interaction between the polymers present in the systems. Additionaly, the physicochemical and rheological properties of xylan were also evaluated. Initially, xylan was extracted from corn cobs and characterized regarding the yield and rheological properties. Afterwards, 10 formulations were prepared in different xylan and ES100 weight ratios by spray-drying the polymer solutions in 0.6N NaOH and phosphate buffer pH 7.4. In addition, 3 formulations consisting of xylan microcapsules were produced by interfacial cross-linking polymerization and coated by ES100 by means of spray-drying in different polymer weight ratios of xylan and ES100. The microparticles were characterized regarding yield, morphology, homogeneity, visual aspect, crystallinity and thermal behavior. The polymer interaction was investigated by infrared spectroscopy. The extracted xylan was presented as a very fine and yellowish powder, with mean particle size smaller than 40μm. Regarding the rheological properties of xylan, they demonstrated that this polymer has a poor flow, low density and high cohesiveness. The microparticles obtained were shown to be spherical and aggregates could not be observed. They were found to present amorphous structure and have a very high thermal stability. The yield varied according to the polymer ratios. Moreover, it was confirmed that the interaction between xylan and ES100 occurs only by means of physical aggregation

Desenvolvimento de sistemas micro e nanoestruturados de quitosana/MDI para aplicações cosméticas

Currently, studies in the area of polymeric microcapsules and nanocapsules and controlled release are considerably advanced. This work aims the study and development of microcapsules and nanocapsules from Chitosan/MDI, using a new technique of interfacial polycondensation combined to spontaneous emulsification, for encapsulation of BZ-3. It was firstly elaborated an experimental design of 23 of the particle in white without the presence of BZ-3 and Miglyol, where the variables were the concentrations of MDI, chitosan and solvent. Starting from the data supplied by the experimental design was chosen the experiment with smaller particle diameter and only added like this BZ-3 and Miglyol. The suspension containing concentrations of 6.25 mg/mL, 12.5 mg/mL, 18.75 mg/mL, 25 mg/mL of BZ-3 were prepared, nevertheless, during the storage time, these formulations presented drug precipitates in the suspensions of 18.75 mg/mL and 25 mg/mL of BZ-3. This apparition of precipitate was attributed to the diffusion of BZ-3 for the aqueous phase without any encapsulation, suggesting so the use of the smaller concentrations of the BZ-3. The suspension containing 6.25mg/mL of BZ3 presented average size of 1.47μm, zeta potential of 61 mV, pH 5.64 and this sample showed an amount of BZ-3 and drug entrapment of 100 %. The suspension containing 12.5mg/mL of BZ-3 presented average size of 1.76μm, zeta potential of 47.4 mV, pH 5.71 and this sample showed an amount of BZ-3 and drug entrapment of 100 %. Then, showing such important characteristics, these two formulations were chosen for futher continuity to the study. These formulations were also characterized by the morphology, FTIR, stability for Turbiscan, DSC and a study of controlled release of the BZ-3 was elaborated in different receiving means

Thermal analysis of chitosan based networks

In this work two kinds of material were studied: chitosan cross-linked with glutaraldehyde and in a blend with PEO. The resulting products as well as chitosan and PEO raw materials, were analyzed by TG/DTG, DSC and DMTA to determinate the in?uence of cross-linking and PEO addition on thermal properties of the resulting materials. It was observed by thermogravimetry that the water-polymer interaction will be different for the cross-linked material compared to the blend, according to the specific site availability. The in?uence of such modifications (cross-linking and PEO addition), on chitosan thermal stability was also studied. The DSC results showed a good agreement with the TG/DTG results, reinforcing the interpretation given for TG/DTG results. DMTA results indicate that glass transition temperature is around 50 degrees C for the polymer under study. (c) 2005 Elsevier Ltd. All rights reserved.

Thin polymer films prepared by plasma immersion ion implantation and deposition

This work describes an investigation of the properties of polymer films prepared by plasma immersion ion implantation and deposition. Films were synthesized from low pressure benzene glow discharges, biasing the samples with 25 W negative pulses. The total energy deposited in the growing layer was varied tailoring simultaneously pulse frequency and duty cycle. The effect of the pulse characteristics on the chemical composition and mechanical properties of the films was studied by X-ray photoelectron spectroscopy (XPS) and nanoindentation, respectively. Analysis of the deconvoluted C 1s XPS peaks demonstrated that oxygen was incorporated in all the samples. The chemical modifications induced structural reorganization, characterized by chain cross-linking and unsaturation, affecting material properties. Hardness and plastic resistance parameter increased under certain bombardment conditions. An interpretation is proposed in terms of the total energy delivered to the growing layer. (C) 2004 Elsevier B.V. All rights reserved.

Investigação do processo de absorção de água de hidrogéis de polissacarídeo: efeito da carga iônica, presença de sais, concentrações de monômero e polissacarídeo

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

Cytotoxicity and Regenerative Proliferation as the Mode of Action for Diuron-Induced Urothelial Carcinogenesis in the Rat

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

Bacterial cellulose-collagen nanocomposite for bone tissue engineering

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

Identification of a new quaternary association for legume lectins

Lotus tetragonolobus lectin (LTA) is a fucose-specific legume lectin. Although several studies report a diverse combination of biological activities for LTA, little is known about the mechanisms involved in L-fucosyl oligosaccharide recognition. The crystal structure of LTA at 2.0 angstrom resolution reveals a different legume lectin tetramer. Its structure consists of a homotetramer composed of two back-to-back GS4-like dimers arranged in a new mode, resulting in a novel tetramer. The LTA N-linked carbohydrate at Asn4 and the unusual LTA dimer-dimer interaction are related to its particular mode of tetramerization. In addition, we used small angle X-ray scattering to investigate the quaternary structure of LTA in solution and to compare it to the crystalline structure. Although the crystal structure of LTA has revealed a conserved metal-binding site, its L-fucose-binding site presents some punctual differences. Our investigation of the new tetramer of LTA and its fucose-binding site is essential for further studies related to cross-linking between LTA and complex divalent L-fucosyl carbohydrates. (C) 2007 Elsevier B.V. All rights reserved.

NMR study of styrene-butadiene rubber (SBR) and TiO2 nanocomposites

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

Influence of cerium (IV) ions on the mechanism of organosilane polymerization and on the improvement of its barrier properties

In this work, the effect of cerium (IV) ammonium nitrate (CAN) addition on the polymerization of bis-[triethoxysilyl]ethane (BTSE) film applied on carbon steel was studied. The electrochemical characterization of the films was carried out in 0.1 mol L(-1) NaCl solution by open-circuit potential measurements, anodic and cathodic polarization curves and electrochemical impedance spectroscopy (EIS). Morphological and chemical characterization were performed by atomic force microscopy (AFM), contact angle measurements, infrared-spectroscopy, nuclear magnetic resonance and thermogravimetric analysis. The results have clearly shown the improvement on the protective properties of the Ce(4+) modified film as a consequence of the formation of a more uniform and densely reticulated silane film. A mechanism is proposed to explain the accelerating role of Ce(4+) ions on the cross-linking of the silane layer. (C) 2008 Elsevier Ltd. All rights reserved.

Hydrophilization of PVC surfaces by argon plasma immersion ion implantation

Commercial polyvinylchloride (PVC) sheets were treated by plasma immersion ion implantation, PIII. Samples were immersed in argon glow discharges and biased with 25 kV negative pulses. Exposure time to the bombardment plasma changed from 900 to 10,800 s. Through contact angle measurements, the effect of the exposure time on the PVC wettability was investigated. Independent of t, all samples presented contact angles, theta, equal to zero after the treatment. However, in some cases, surface hydrophilization was not stable, as revealed by the temporal evolution of theta. Samples bombarded for shorter periods recovered partially or totally the hydrophobic character while the one exposed for the longest time stayed highly hydrophilic. These modifications are ascribed to the Cl loss and O incorporation as shown by XPS measurements. Furthermore, the mobility of surface polar groups and the variation in the cross-linking degree can also affect the PVC wettability.

Silica-PEG hybrid ormolytes: structure and properties

The effect of lithium salt doping on the structure and ionic conduction properties of silica-polyethyleneglycol composites is reported. These materials, so called ormolytes (organically modified electrolytes), were obtained by the sol-gel process. They have chemical stability due to the covalent bonds between the inorganic (silica) and organic (polymer) phase. The structure of these hybrid materials was investigated by small-angle X-ray scattering (SAXS) as a function of lithium concentration [O]/[Li] (O being the oxygens of the ether type). The spectra have a well-defined peak attributed to the existence of a liquid-like spatial correlation of silica clusters. The ionic conductivity was studied by AC impedance spectroscopy and is maximum for [O]/[Li] = 15. This result is consistent with SAXS and thermo-mechanical analysis measurements and is due to the formation of cross-linking between the polymer chains for the larger lithium concentrations. These materials are solid, transparent, flexible and have an ionic conductivity up to 10(-4) S/cm. (C) 1999 Elsevier B.V. B.V. All rights reserved.

High hydrostatic pressure processing on microstructure of probiotic low-fat yogurt

The effect of milk processing on the microstructure of probiotic low-fat yogurt was studied. Skim milk fortified with skim milk powder was subjected to three treatments prior to innoculation: thermal treatment at 85 degrees C for 30 min, high hydrostatic pressure at 676 MPa for 5 min, and combined treatments of high hydrostatic pressure (HHP) and heat. The processed milk was then fermented by using two different starter cultures containing Streptococcus thermophilus, Lactobacillus delbrueckii ssp. bulgaricus, Lactobacillus acidophilus, and Bifidobacterium longum. The microstructure of heat-treated milk yogurt had fewer interconnected chains of irregularly shaped casein micelles, forming a network that enclosed the void spaces. on the other hand, microstructure of HHP yogurt had more interconnected clusters of densely aggregated protein of reduced particle size, with an appearance more spherical in shape, exhibiting a smoother more regular surface and presenting more uniform size distribution. The combined HHP and heat milk treatments led to compact yogurt gels with increasingly larger casein micelle clusters interspaced by void spaces, and exhibited a high degree of cross-linking. The rounded micelles tended to fuse and form small irregular aggregates in association with clumps of dense amorphous material, which resulted in improved gel texture and viscosity. (C) 2007 Elsevier Ltd. All rights reserved.

The effect of N+ ion energy on the properties of ion bombarded plasma polymer films

This work describes the influence of the ion bombardment on the electrical, optical and mechanical properties of polymer films deposited from radio-frequency plasmas of benzene. Irradiations were conducted using N+ at 5 x 10(19) ions/m(2), varying the ion energy, E-0, from 0 to 150 keV. Film elemental composition was determined by Rutherford backscattering spectroscopy. Electrical resistivity and hardness were obtained by the two-point probe and nanoindentation technique, respectively. Ultraviolet-visible spectroscopy was employed to investigate the optical constants of the samples. Etching rate was determined by exposure of the films to reactive oxygen plasmas. Ion bombardment induced gradual loss of H and increase in C and O concentrations with Eo. As a consequence the electrical, optical and mechanical properties were drastically affected. Interpretation of these results is proposed in terms of chain cross-linking and unsaturation. (C) 2001 Elsevier B.V. B.V. All rights reserved.