Physical characterisation and component release of poly(vinyl alcohol)-tetrahydroxyborate hydrogels and their applicability as potential topical drug delivery systems

Poly(vinyl alcohol)-tetrahydroxyborate (PVA-THB) hydrogels are dilatant formulations with potential for topical wound management. To support this contention, the physical properties, rheological behaviour and component release of candidate formulations were investigated. Oscillatory rheometry and texture profile analysis were used at room temperature and 37 °C. Results showed that it was possible to control the rheological and textural properties by altering component concentration and modifying the type of PVA polymer used. Hydrogels made using PVA grades with higher degrees of hydrolysis displayed favourable characteristics from a wound healing perspective. In vitro release of borate and PVA were assessed in order to evaluate potential clinical dosing of free species originating from the hydrogel structure. Component diffusion was influenced by both concentration and molecular weight, where relevant, with up to 5% free PVA cumulative release observed after 30 min. The results of this study demonstrated the importance of poly(vinyl alcohol) selection for ensuring appropriate gel formation in PVA-THB hydrogels. The benefits of higher degrees of hydrolysis, in particular, included lower excipient release and reduced bioadhesion. The unique physical characteristics of these hydrogels make them an appealing delivery vehicle for chronic and acute wound management purposes.

Modified Discrete PSO to Increase the Delivered Energy Probability in Distribution energy Systems

This paper proposes a PSO based approach to increase the probability of delivering power to any load point by identifying new investments in distribution energy systems. The statistical failure and repair data of distribution components is the main basis of the proposed methodology that uses a fuzzyprobabilistic modeling for the components outage parameters. The fuzzy membership functions of the outage parameters of each component are based on statistical records. A Modified Discrete PSO optimization model is developed in order to identify the adequate investments in distribution energy system components which allow increasing the probability of delivering power to any customer in the distribution system at the minimum possible cost for the system operator. To illustrate the application of the proposed methodology, the paper includes a case study that considers a 180 bus distribution network.

High-amylose carboxymethyl starch matrices for oral sustained drug-release : in vitro and in vivo evaluation

Les amidons non modifiées et modifiés représentent un groupe d’excipients biodégradables et abondants particulièrement intéressant. Ils ont été largement utilisés en tant qu’excipients à des fins diverses dans des formulations de comprimés, tels que liants et/ou agents de délitement. Le carboxyméthylamidon sodique à haute teneur en amylose atomisé (SD HASCA) a été récemment proposé comme un excipient hydrophile à libération prolongée innovant dans les formes posologiques orales solides. Le carboxyméthylamidon sodique à haute teneur en amylose amorphe (HASCA) a d'abord été produit par l'éthérification de l'amidon de maïs à haute teneur en amylose avec le chloroacétate. HASCA a été par la suite séché par atomisation pour obtenir le SD HASCA. Ce nouvel excipient a montré des propriétés présentant certains avantages dans la production de formes galéniques à libération prolongée. Les comprimés matriciels produits à partir de SD HASCA sont peu coûteux, simples à formuler et faciles à produire par compression directe. Le principal objectif de cette recherche était de poursuivre le développement et l'optimisation des comprimés matriciels utilisant SD HASCA comme excipient pour des formulations orales à libération prolongée. A cet effet, des tests de dissolution simulant les conditions physiologiques du tractus gastro-intestinal les plus pertinentes, en tenant compte de la nature du polymère à l’étude, ont été utilisés pour évaluer les caractéristiques à libération prolongée et démontrer la performance des formulations SD HASCA. Une étude clinique exploratoire a également été réalisée pour évaluer les propriétés de libération prolongée de cette nouvelle forme galénique dans le tractus gastro-intestinal. Le premier article présenté dans cette thèse a évalué les propriétés de libération prolongée et l'intégrité physique de formulations contenant un mélange comprimé de principe actif, de chlorure de sodium et de SD HASCA, dans des milieux de dissolution biologiquement pertinentes. L'influence de différentes valeurs de pH acide et de temps de séjour dans le milieu acide a été étudiée. Le profil de libération prolongée du principe actif à partir d'une formulation de SD HASCA optimisée n'a pas été significativement affecté ni par la valeur de pH acide ni par le temps de séjour dans le milieu acide. Ces résultats suggèrent une influence limitée de la variabilité intra et interindividuelle du pH gastrique sur la cinétique de libération à partir de matrices de SD HASCA. De plus, la formulation optimisée a gardé son intégrité pendant toute la durée des tests de dissolution. L’étude in vivo exploratoire a démontré une absorption prolongée du principe actif après administration orale des comprimés matriciels de SD HASCA et a montré que les comprimés ne se sont pas désintégrés en passant par l'estomac et qu’ils ont résisté à l’hydrolyse par les α-amylases dans l'intestin. Le deuxième article présente le développement de comprimés SD HASCA pour une administration orale une fois par jour et deux fois par jour contenant du chlorhydrate de tramadol (100 mg et 200 mg). Ces formulations à libération prolongée ont présenté des valeurs de dureté élevées sans nécessiter l'ajout de liants, ce qui facilite la production et la manipulation des comprimés au niveau industriel. La force de compression appliquée pour produire les comprimés n'a pas d'incidence significative sur les profils de libération du principe actif. Le temps de libération totale à partir de comprimés SD HASCA a augmenté de manière significative avec le poids du comprimé et peut, de ce fait, être utilisé pour moduler le temps de libération à partir de ces formulations. Lorsque les comprimés ont été exposés à un gradient de pH et à un milieu à 40% d'éthanol, un gel très rigide s’est formé progressivement sur leur surface amenant à la libération prolongée du principe actif. Ces propriétés ont indiqué que SD HASCA est un excipient robuste pour la production de formes galéniques orales à libération prolongée, pouvant réduire la probabilité d’une libération massive de principe actif et, en conséquence, des effets secondaires, même dans le cas de co-administration avec une forte dose d'alcool. Le troisième article a étudié l'effet de α-amylase sur la libération de principe actif à partir de comprimés SD HASCA contenant de l’acétaminophène et du chlorhydrate de tramadol qui ont été développés dans les premières étapes de cette recherche (Acetaminophen SR et Tramadol SR). La modélisation mathématique a montré qu'une augmentation de la concentration d’α-amylase a entraîné une augmentation de l'érosion de polymère par rapport à la diffusion de principe actif comme étant le principal mécanisme contrôlant la libération de principe actif, pour les deux formulations et les deux temps de résidence en milieu acide. Cependant, même si le mécanisme de libération peut être affecté, des concentrations d’α-amylase allant de 0 UI/L à 20000 UI/L n'ont pas eu d'incidence significative sur les profils de libération prolongée à partir de comprimés SD HASCA, indépendamment de la durée de séjour en milieu acide, le principe actif utilisé, la teneur en polymère et la différente composition de chaque formulation. Le travail présenté dans cette thèse démontre clairement l'utilité de SD HASCA en tant qu'un excipient à libération prolongée efficace.

Second meal effect: modified sham feeding does not provoke the release of stored triacylglycerol from a previous high-fat meal

The present study was carried out to determine whether cephalic stimulation, associated with eating a meal, was sufficient stimulus to provoke the release of stored triacylglycerol (TAG) from a previous high-fat meal. Ten subjects were studied on three separate occasions. Following a 12 h overnight fast, subjects were given a standard mixed test meal which contained 56 g fat. Blood samples were taken before the meal and for 5 h after the meal when the subjects were randomly allocated to receive either water (control) or were modified sham fed a low-fat (6 g fat) or moderate-fat (38 g fat) meal. Blood samples were collected for a further 3 h. Compared with the control, modified sham feeding a low- or moderate-fat meal did not provoke an early entry of TAG, analysed in either plasma or TAG-rich lipoprotein (TRL) fraction (density ,1´006 kg/l). The TRL-retinyl ester data showed similar findings. A cephalic phase secretion of pancreatic polypeptide, without a significant increase in cholecystokinin levels, was observed on modified sham feeding. Although these data indicate that modified sham feeding was carried out successfully, analysis of the fat content of the expectorant showed that our subjects may have accidentally ingested a small amount of fat (0´7 g for the low-fat meal and 2´4 g for the moderate-fat meal). Nevertheless, an early TAG peak following modified sham feeding was not demonstrated in the present study, suggesting that significant ingestion of food, and not just orosensory stimulation, is necessary to provoke the release of any TAG stored from a previous meal.

The study of chiral adsorption systems using synchrotron- based structural and spectroscopic techniques: stereospecific adsorption of serine on Au-modified chiral Cu{531} surfaces

We apply modern synchrotron-based structural techniques to the study of serine adsorbed on the pure andAumodified intrinsically chiral Cu{531} surface. XPS and NEXAFS data in combination with DFT show that on the pure surface both enantiomers adsorb in l4 geometries (with de-protonated b-OH groups) at low coverage and in l3 geometries at saturation coverage. Significantly larger enantiomeric differences are seen for the l4 geometries, which involve substrate bonds of three side groups of the chiral center, i.e. a three-point interaction. The l3 adsorption geometry, where only the carboxylate and amino groups form substrate bonds, leads to smaller but still significant enantiomeric differences, both in geometry and the decomposition behavior. When Cu{531} is modified by the deposition of 1 and 2ML Au the orientations of serine at saturation coverage are significantly different from those on the clean surface. In all cases, however, a l3 bond coordination is found at saturation involving different numbers of Au atoms, which leads to relatively small enantiomeric differences.

Privacy preserving data release for tagging recommender systems

Tagging recommender systems allow Internet users to annotate resources with personalized tags. The connection among users, resources and these annotations, often called a folksonomy, permits users the freedom to explore tags, and to obtain recommendations. Releasing these tagging datasets accelerates both commercial and research work on recommender systems. However, tagging recommender systems has been confronted with serious privacy concerns because adversaries may re-identify a user and her/his sensitive information from the tagging dataset using a little background information. Recently, several private techniques have been proposed to address the problem, but most of them lack a strict privacy notion, and can hardly resist the number of possible attacks. This paper proposes an private releasing algorithm to perturb users' profile in a strict privacy notion, differential privacy, with the goal of preserving a user's identity in a tagging dataset. The algorithm includes three privacy-preserving operations: Private Tag Clustering is used to shrink the randomized domain and Private Tag Selection is then applied to find the most suitable replacement tags for the original tags. To hide the numbers of tags, the third operation, Weight Perturbation, finally adds Laplace noise to the weight of tags. We present extensive experimental results on two real world datasets, De.licio.us and Bibsonomy. While the personalization algorithm is successful in both cases, our results further suggest the private releasing algorithm can successfully retain the utility of the datasets while preserving users' identity.

Semisolid systems containing propolis for the treatment of periodontal disease: In vitro release kinetics, syringeability, rheological, textural, and mucoadhesive properties

Formulations containing poloxamer 407 (P407), carbopol 934P (C934P), and propolis extract (PE) were designed for the treatment of periodontal disease. Gelation temperature, in vitro drug release, rheology, hardness, compressibility, adhesiveness, mucoadhesion, and syringeability of formulations were determined. Propolis release from formulations was controlled by the phenomenon of relaxation of polymer chains. Formulations exhibited pseudoplastic flow and low degrees of thixotropy or rheopexy. In most samples, increasing the concentration of C934P content significantly increased storage modulus (G'), loss modulus (G ''), and dynamic viscosity (n') at 5 degrees C, G '' exceeded G'. At 25 and 37 degrees C, n' of each formulation depended on the oscillatory frequency. Formulations showed thermoresponsive behavior, existing as a liquid at room temperature and gel at 34-37 degrees C. Increasing the C934P content or temperature significantly increased formulation hardness, compressibility, and adhesiveness. The greatest mucoadhesion was noted in the formulation containing 15% P407 (w/w) and 0.25% C934P (w/w). The work of syringeability values of all formulations were similar and very desirable with regard to ease of administration. The data obtained in these formulations indicate a potentially useful role in the treatment of periodontitis and suggest they are worthy of clinical evaluation. (c) 2007 Wiley-Liss, Inc.

Alginate-chitosan systems: In vitro controlled release of triamcinolone and in vivo gastrointestinal transit

The aim of this study was to develop multiparticulate therapeutic systems of alginate (AL) and chitosan (CS) containing triamcinolone (TC) to colonic drug delivery. Multiparticulate systems of AL-CS, prepared by a complex coacervation/ionotropic gelation method, were characterized for morphological and size aspects, swelling degree, encapsulation content and efficiency, in vitro release profile in different environments simulating the gastrointestinal tract (GIT) and in vivo gastrointestinal transit. The systems showed suitable morphological characteristics with particle diameters of approximately 1.6 mm. In simulated gastric environment, at pH 1.2, the capsules presented low degree of swelling and in vitro release of drug. A higher swelling degree was observed in simulated enteric environment, pH 7.5, followed by erosion. Practically all the drug was released after 6 h of in vitro assay. The in vivo analysis of gastrointestinal transit, carried out in rats, showed that the systems passed practically intact through the stomach and did not show the same profile of swelling observed in the in vitro tests. It was possible to verify the presence of capsules in the colonic region of GIT. The results indicate that AL-CS multiparticulate systems can be used as an adjuvant for the preparation of therapeutic systems to colonic delivery of drugs. (C) 2010 Elsevier Ltd. All rights reserved.

Short-term in situ/ex vivo study of the anticariogenic potential of a resin-modified glass-ionomer cement associated with adhesive systems

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Multiparticulate systems of pectin-chitosan: Study of swelling and drug release

The aim of this study was to prepare multiparticulate systems of pectin:chitosan (PC:CS) and to evaluate their swelling ratio and the drug release in different environments. PC:CS particles containing triamcinolone were prepared by a complex coacervation/ionotropic gelation method in aqueous environment. The polymer ratio, the calcium concentration and the contact time of the capsules with chitosan dispersion for particles formation and the structures obtained were analyzed. The systems were characterized in relation to morphology, size, swelling, and drug release behavior. The methodology used allowed the production of spherical particles with narrow range of size distribution. The entrapment efficiency for triamcinolone was 84.31 ± 439. It was observed that the particles present a relatively low swelling ratio in acidic medium and a larger swelling ratio in enteric medium. The release profile was dependent on pH and can be related with the swelling ratio.

Reconfiguration of distribution systems by a modified genetic algorithm

In this paper a genetic algorithm based reconfiguration method is proposed to minimize the real power losses of distribution systems. The main innovation of this research work is that new types of crossover and mutation operators are proposed, such that the best possible results are obtained, with an acceptable computational effort. The crossover and mutation operators were developed so as to take advantage of the particular characteristics of distribution systems (as the radial topology). Simulation results indicate that the proposed method is very efficient, being able to find excellent configurations, with low computational effort, especially for larger systems. ©2007 IEEE.

Pluronics F-127/L-81 Binary Hydrogels as Drug-Delivery Systems: Influence of Physicochemical Aspects on Release Kinetics and Cytotoxicity

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

Fluoride release and secondary caries inhibition by adhesive systems on root dentine

This study tested the fluoride-release rate and the root caries inhibitory effect of dental adhesives. In phase 1, the fluoride released from samples (n = 5) of the adhesives A (Optibond Solo), B (One-up Bond F), C (Prime & Bond NT), D (Tenure Quick), and also of the controls [+] (glass-ionomer cement) and [-] (non-fluoride releasing adhesive), was quantified on a daily basis during a pH-cycling, caries-simulating phenomenon. In phase 2, restorations were made in bovine root dentine slabs (n = 16) with the same adhesives associated with a non-fluoridated composite. Control [+] restorations were made entirely with glass-ionomer cement. Specimens were thermocycled and submitted to the pH-cycling regimen. Demineralization areas and the presence of the wall lesion (WL) and the inhibition zone (IZ) were determined by polarizing light microscopy in dentine adjacent to the restoration. The highest concentration of fluoride was released by the control [+]; adhesives A, B and C, also released fluoride. No detectable amount of fluoride was released by D or [-]. Smaller areas of demineralization were found with control [+], whereas the demineralization areas of adhesives A-D and [-] did not differ from each other. No WL was detected, and higher percentages of IZ were recorded to [+] and to adhesive A. Although some dental adhesives were able to release fluoride, they could not inhibit secondary caries development as well as the glass-ionomer cement.

Doxycycline-Encapsulated Nanotube-Modified Dentin Adhesives

This article presents details of fabrication, biological activity (i.e., anti-matrix metalloproteinase [anti-MMP] inhibition), cytocompatibility, and bonding characteristics to dentin of a unique doxycycline (DOX)-encapsulated halloysite nanotube (HNT)-modified adhesive. We tested the hypothesis that the release of DOX from the DOX-encapsulated nanotube-modified adhesive can effectively inhibit MMP activity. We incorporated nanotubes, encapsulated or not with DOX, into the adhesive resin of a commercially available bonding system (Scotchbond Multi-Purpose [SBMP]). The following groups were tested: unmodified SBMP (control), SBMP with nanotubes (HNT), and DOX-encapsulated nanotube-modified adhesive (HNT+DOX). Changes in degree of conversion (DC) and microtensile bond strength were evaluated. Cytotoxicity was examined on human dental pulp stem cells (hDPSCs). To prove the successful encapsulation of DOX within the adhesivesbut, more important, to support the hypothesis that the HNT+DOX adhesive would release DOX at subantimicrobial levelswe tested the antimicrobial activity of synthesized adhesives and the DOX-containing eluates against Streptococcus mutans through agar diffusion assays. Anti-MMP properties were assessed via -casein cleavage assays. Increasing curing times (10, 20, 40 sec) led to increased DC values. There were no statistically significant differences (p > .05) in DC within each increasing curing time between the modified adhesives compared to SBMP. No statistically significant differences in microtensile bond strength were noted. None of the adhesives eluates were cytotoxic to the human dental pulp stem cells. A significant growth inhibition of S. mutans by direct contact illustrates successful encapsulation of DOX into the experimental adhesive. More important, DOX-containing eluates promoted inhibition of MMP-1 activity when compared to the control. Collectively, our findings provide a solid background for further testing of encapsulated MMP inhibitors into the synthesis of therapeutic adhesives that may enhance the longevity of hybrid layers and the overall clinical performance of adhesively bonded resin composite restorations.