Evaluating and optimizing oral formulations of live bacterial vaccines using a gastro-small intestine model

Gastrointestinal (GI) models that mimic physiological conditions in vitro are important tools for developing and optimizing biopharmaceutical formulations. Oral administration of live attenuated bacterial vaccines (LBV) can safely and effectively promote mucosal immunity but new formulations are required that provide controlled release of optimal numbers of viable bacterial cells, which must survive gastrointestinal transit overcoming various antimicrobial barriers. Here, we use a gastro-small intestine gut model of human GI conditions to study the survival and release kinetics of two oral LBV formulations: the licensed typhoid fever vaccine Vivotif comprising enteric coated capsules; and an experimental formulation of the model vaccine Salmonella Typhimurium SL3261 dried directly onto cast enteric polymer films and laminated to form a polymer film laminate (PFL). Neither formulation released significant numbers of viable cells when tested in the complete gastro-small intestine model. The poor performance in delivering viable cells could be attributed to a combination of acid and bile toxicity plus incomplete release of cells for Vivotif capsules, and to bile toxicity alone for PFL. To achieve effective protection from intestinal bile in addition to effective acid resistance, bile adsorbent resins were incorporated into the PFL to produce a new formulation, termed BR-PFL. Efficient and complete release of 4.4x107 live cells per dose was achieved from BR-PFL at distal intestinal pH, with release kinetics controlled by the composition of the enteric polymer film, and no loss in viability observed in any stage of the GI model. Use of this in vitro GI model thereby allowed rational design of an oral LBV formulation to maximize viable cell release.

Substitutional Impurities in PPV Crystals: An Intrinsic Donor-Acceptor System for High V(oc) Photovoltaic Devices

Defects are usually present in organic polymer films and are commonly invoked to explain the low efficiency obtained in organic-based optoelectronic devices. We propose that controlled insertion of substitutional impurities may, on the contrary, tune the optoelectronic properties of the underivatized organic material and, in the case studied here, maximize the efficiency of a solar cell. We investigate a specific oxygen-impurity substitution, the keto-defect -(CH(2)-C=O)- in underivatized crystalline poly(p-phenylenevinylene) (PPV), and its impact on the electronic structure of the bulk film, through a combined classical (force-field) and quantum mechanical (DFT) approach. We find defect states which suggest a spontaneous electron hole separation typical of a donor acceptor interface, optimal for photovoltaic devices. Furthermore, the inclusion of oxygen impurities does not introduce defect states in the gap and thus, contrary to standard donor-acceptor systems, should preserve the intrinsic high open circuit voltage (V(oc)) that may be extracted from PPV-based devices.

Laser microstructuring of azopolymers via surface relief gratings: controlling hydrophobicity

In this paper the large-scale mass transport mechanism is used to microstructure azopolymeric films, aiming at controllable hydrophobic surfaces. Using an Ar(+) laser with intensity of 70 mW/cm(2), we produced egg-crate-like surfaces with periods from 1.0 to 3.5 mu m that present distinct wetting properties. The static contact angle of water was measured on the microstructured surfaces, and the results revealed an increase of approximately 9 degrees for a surface pattern period of 2 mu m. Our results indicate the use of the microstructuring method described here for the fabrication of devices with controllable hydrophobicity.

Optical VOCs detection using poly(3-alkylthiophenes) with different side-chain lengths

The use of conjugated polymers in the gas and volatile organic compounds (VOCs) detections represents an advance in the development of the electronic noses. Polythiophenes show good thermal and environmental stability, are easily synthesized and they have been studied as gas and VOCs sensors using different principles or transduction techniques. Among these techniques, optical sensing has been attracted attention, mainly due to its versatility. However, conjugated polymer-based optical sensors are still less studied. This paper describes the use of two poly(3-alkylthiophenes) for VOCs optical detection. The sensing measurements were carried out using visible spectroscopy. Both polymers showed good sensitivity to the VOCs, showing fast and reversible responses with some hysteresis, and were unable to detect hydroxylated samples. Furthermore, it was demonstrated that the thickness of polymer films influences the intensity of the optical response. Although there is similarity in the superficial composition of the polymers films, demonstrated by their surface energies, they showed significant differences in their optical properties upon exposure to the VOCs. (c) 2009 Elsevier B.V. All rights reserved.

Solution behavior and surface properties of carboxymethylcellulose acetate butyrate

Solution behavior of carboxymethylcellulose acetate butyrate (CMCAB) in acetone and ethyl acetate has been investigated by small-angle X-ray scattering (SAXS) and capillary viscometry and correlated with the characteristics of CMCAB films. Viscosity and SAXS measurements showed that ethyl acetate is a better solvent than acetone for CMCAB. Thin films of CMCAB were deposited onto silicon wafers (Si/SiO(2)) by spin coating. AFM images revealed that CMCAB spin coated films from solutions prepared in ethyl acetate were homogeneous and flat. However, films obtained from solutions in acetone were very rough. Contact angle measurements with polar and apolar test liquids characterized CMCAB surfaces as hydrophobic and allowed estimating the surface energy of CMCAB. Sum frequency generation vibrational spectroscopy was used to understand the role played by solvents and to gain insight about molecular orientation at Si/SiO(2)/CMCAB interface.

Electrochemical sensor for sulfite determination based on a nanostructured copper-salen film modified electrode

The electrochemical preparation described herein involved the electrocatalytic oxidation of sulfite on a platinum electrode modified with nanostructured copper salen (salen=N,N'-ethylenebis(salicylideneiminato)) polymer films. The complex was prepared and electropolymerized at a platinum electrode in a 0.1 mol L-1 solution of tetrabutylammonium perchlorate in acetonitrile by cyclic voltammetry between 0 and 1.4V vs. SCE. After cycling the modified electrode in a 0.50 mol L-1 KCI solution, the estimated surface concentration was found to be equal to 2.2 x 10(-9) Mol cm(-2). This is a typical behavior of an electrode surface immobilized with a redox couple that can usually be considered as a reversible single-electron reduction/oxidation of the copper(II)/copper(III) couple. The potential peaks of the modified electrode in the electrolyte solution (aqueous) containing the different anions increase with the decrease of the ionic radius, demonstrating that the counter-ions influence the voltammetric behavior of the sensor. The potential peak was found to be linearly dependent upon the ratio [ionic charge]/[ionic radius]. The oxidation of the sulfite anion was performed at the platinum electrode at +0.9V vs. SCE. However, a significant decrease in the overpotential (+0.45V) was obtained while using the sensor, which minimized the effect of oxidizable interferences. A plot of the anodic current vs. the sulfite concentration for chronoamperometry (potential fixed = +0.45V) at the sensor was linear in the 4.0 x 10(-6) to 6.9 x 10(-5) mol L-1 concentration range and the concentration limit was 1.2 x 10(-6) mol L-1. The reaction order with respect to sulfite was determined by the slope of the logarithm of the current vs. the logarithm of the sulfite concentration. (C) 2009 Elsevier Ltd. All rights reserved.

Thermomechanical characterization of PVDF and P(VDF-TrFE) blends containing corn starch and natural rubber

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

Analysis of the Al-PANI interfaces by complex impedance spectroscopy

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Argon ion implantation inducing modifications in the properties of benzene plasma polymers

Benzene plasma polymer films were bombarded with Ar ions by plasma immersion ion implantation. The treatments were performed using argon pressure of 3 Pa and 70 W of applied power. The substrate holder was polarized with high voltage negative pulses (25 kV, 3 Hz). Exposure time to the immersion plasma, t, was varied from 0 to 9000 s. Optical gap and chemical composition of the samples were determined by ultraviolet-visible and Rutherford backscattering spectroscopies, respectively. Film wettability was investigated by the contact angle between a water drop and the film surface. Nanoindentation technique was employed in the hardness measurements. It was observed growth in carbon and oxygen concentrations while there was decrease in the concentration of H atoms with increasing t. Furthermore, film hardness and wettability increased and the optical gap decreased with t. Interpretation of these results is proposed in terms of the chain crosslinking and unsaturation. (C) 2002 Elsevier B.V. B.V. All rights reserved.

AN ACTINOMETRIC STUDY OF C2H2 PLASMA POLYMERIZATION AND FILM PROPERTIES

Thin polymer films were grown in radio frequency discharges containing C2H2. Actinometry revealed the trend in the plasma concentration of the CH species as a function of the operating pressure. The C-H bond density in the films, revealed by infrared analysis, was found to increase with the pressure of C2H2 in a similar way to that of the concentration of the CH species in the discharge. From transmission ultraviolet-visible spectroscopy data, optical parameters of the polymers, namely, the refractive index and the optical gap, were calculated. For the range of pressure studied, the refractive index decreased from 1.73 to 1.63 and the optical gap increased from 2.4 to 3.3 eV. Finally, measurements of the residual stress of the polymer films were carried out by the bending beam method, using a He-Ne laser, yielding values from 0.05 to 0.3 GPa. (C) 1995 American Vacuum Society.

Surface modifications on Teflon FEP and Mylar C induced by a low energy electron beam: a Raman and FTIR spectroscopic study

The surface modifications induced on Teflon FEP and Mylar C polymer films by a low energy electron beam are probed using Raman and FTIR spectroscopy. The electron beam, which does not affect the Mylar C, surface, may break the copolymer chain into its monomers degrading the Teflon FEP surface. For Mylar C the electron beam decreases the roughness of the polymer surface. This difference in behavior may explain recent results in which the surface modifications investigated by measuring the second crossover energy shift in the electronic emission curve differed for the two polymers (Chinaglia et al [1]). In addition, the Raman data showed no evidence of carbon formation for either polymer samples, which is explained by the fact that only a low energy electron beam is used.

Magnetic field release of trapped charges in poly(fluorenylenevinylene)s

We have measured the effect of an applied magnetic field on the current through thin films of two different organic conjugated polymers that have previously shown to exhibit magnetoresistance, poly(9,9-dioctyl-1,4-fluorenylenevinylene) and poly(9,9-dioctyl-2,7-fluorenylenevinylene). The results show that the magnetic field releases trapped charges from inside the material and enhances the current. We have also performed optical absorption experiments on these polymer films under applied voltage and magnetic field. The results show that the magnetic field produces a change in the optical absorption in the low-energy range associated with deep traps and only under conditions when these traps are likely charged. These two results provide a strong case for the release of trapped charges caused by the magnetic field as being the cause of the magneto resistance in these polymers and possibly in other organic materials where magnetoresistance was recently observed. (c) 2007 Elsevier B.V. All rights reserved.

Plasma polymerized hexamethyldisiloxane: Discharge and film studies

Films were grown in hexamethyldisiloxane (HMDS)-argon mixtures in a diode sputtering system with a gold cathode. Quantitative optical emission spectroscopy (OES)-actinometry revealed that the electron density or mean electron energy (or both) increased with increasing Ar concentrations in the gas feed. Increasing concentrations of Ar produced greater sputtering of the cathode and hence greater plasma A u concentrations. Fragmentation of the HMDS molecule resulted in species such as CH, Fl, and Si which were detected by OES. Film deposition rate, as determined by optical interferometry, was found to be increased by the inclusion of Ar in the gas feed. Transmission electron microscopy revealed particles, probably of Au, embedded in the polymer films. Actinometric measurements of Au in the discharge and electron probe microscopy of the deposited material showed that film Au concentrations increase with increasing concentrations of Au in the plasma. A relatively low fragmentation of HMDS molecules in the de plasma was revealed by the very small Si-HIR absorption band which is usually prominent in spectra of plasma polymerized HMDS films.

Effects of helium ion irradiation on fluorinated plasma polymers

The effects of ion irradiation on fluorinated plasma polymer films are investigated using profilometry, surface contact-angle measurements, infrared reflection absorption spectroscopy (IRRAS) and X-ray photoelectron spectroscopy (XPS). Remarkably, helium plasma immersion ion implantation (PIII) of several amorphous hydrogenated fluorinated plasma polymers deposited from C(2)H(2)-SF(6), C(6)H(6)-SF(6) or C(6)F(6) produces film compactions of up to 40%, and modifies the surface energy in the 35 to 65 dyn cm(-1) range. As revealed by IRRAS and XPS, the films contain C-H, C-C, C=C, C=O, O-H and C-F groups. XPS spectra confirm the presence of N (typically similar to 5%). The films produced from SF(6)-containing plasmas also contain S. For irradiation times of 80 min, the film carbon content is increased, and the fluorine content is greatly reduced, by factors of about 3 to 15, depending on the initial film composition. (C) 2010 Elsevier B.V. All rights reserved.

A Novel Plasma Technique for Surface Treatment: The Plasma Expander

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