Estudos das interações de quitosana/CTAB/C12E8

Surfactant-polymer interactions are widely used when required rheological properties for specific applications, such as the production of fluids for oil exploration. Studies of the interactions of chitosan with cationic surfactants has attracted attention by being able to cause changes in rheological parameters of the systems making room for new applications. The commercial chitosan represents an interesting alternative to these systems, since it is obtained from partial deacetylation of chitin: the residues sites acetylated can then be used for the polymer-surfactant interactions. Alkyl ethoxylated surfactants can be used in this system, since these non-ionic surfactants can interact with hydrophobic sites of chitosan, modifying the rheology of solutions or emulsions resultants, which depends on the relaxation phenomenon occurring in these systems. In this work, first, inverse emulsions were prepared from chitosan solution as the dispersed phase and cyclohexane as the continuous phase were, using CTAB as a surfactant. The rheological analysis of these emulsions showed pronounced pseudoplastic behavior. This behavior was attributed to interaction of "loops" of chitosan chains. Creep tests were also performed and gave further support to these discussions. Subsequently, in order to obtain more information about the interaction of chitosan with non-ionic surfactants, solutions of chitosan were mixed with C12E8 and and carried out rheological analysis and dynamic light scattering. The systems showed marked pseudoplastic behavior, which became less evident when the concentration of surfactant was increased. Arrhenius and KWW equations were used to obtain parameters of the apparent activation energy and relaxation rate distribution, respectively, to which were connected to the content of surfactant and temperature used in this work

Molecular Variations In Aromatic Cosolutes: Critical Role In The Rheology Of Cationic Wormlike Micelles.

Wormlike micelles formed by the addition to cetyltrimethylammonium bromide (CTAB) of a range of aromatic cosolutes with small molecular variations in their structure were systematically studied. Phenol and derivatives of benzoate and cinnamate were used, and the resulting mixtures were studied by oscillatory, steady-shear rheology, and the microstructure was probed by small-angle neutron scattering. The lengthening of the micelles and their entanglement result in remarkable viscoelastic properties, making rheology a useful tool to assess the effect of structural variations of the cosolutes on wormlike micelle formation. For a fixed concentration of CTAB and cosolute (200 mmol L(-1)), the relaxation time decreases in the following order: phenol > cinnamate> o-hydroxycinnamate > salicylate > o-methoxycinnamate > benzoate > o-methoxybenzoate. The variations in viscoelastic response are rationalized by using Mulliken population analysis to map out the electronic density of the cosolutes and quantify the barrier to rotation of specific groups on the aromatics. We find that the ability of the group attached to the aromatic ring to rotate is crucial in determining the packing of the cosolute at the micellar interface and thus critically impacts the micellar growth and, in turn, the rheological response. These results enable us for the first time to propose design rules for the self-assembly of the surfactants and cosolutes resulting in the formation of wormlike micelles with the cationic surfactant CTAB.

Effect of temperature on the interaction between the nonionic surfactant C(12)E(5) and poly(ethylene oxide) investigated by dynamic light scattering and fluorescence methods

The interaction between the nonionic surfactant C(12)E(5) and a high molar mass (M = 5.94 x 10(5)) poly(ethylene oxide) (PEG) in aqueous solution has been examined as a function of temperature by dynamic light scattering and fluorescence methods over a broad concentration range. Clusters of small surfactant micelles form within the PEO coil, leading to its extension. The hydrodynamic radius of the complex increases strongly with temperature as well as with the concentrations of surfactant and polymer. At high concentrations of the surfactant, the coil/micellar cluster complex coexists with free C(12)E(5) micelles in the solution. Fluorescence quenching measurements show a moderate micellar growth from 155 to 203 monomers in PEO-free solutions of C(12)E(5) over a wide concentration range (0.02-2.5%) at 8 degrees C. Below 0.25% C(12)E(5), the average aggregation number (N) of the micelles is smaller in the presence of PEO than in its absence. However, N increases with increasing surfactant concentration up to a plateau value of about 270 at about 1.2% (ca. 30 mM) C(12)E(5). At high surfactant concentrations, N is larger in the presence of polymer than in its absence, a finding which is connected to a significant lowering of the clouding temperature due to the PEO at these compositions. Similar results of increasing aggregation number followed by a plateau were also found at a fixed concentration of surfactant (2.5%) and varied PEO.

Interactions between the non-ionic surfactant C(12)E(5) and poly(ethylene oxide) studied using dynamic light scattering and fluorescence quenching

Dynamic light scattering measurements have been made to elucidate changes in the coil conformation of a high molecular weight poly(ethylene oxide) (PEG) fraction when the non-ionic surfactant C(12)E(5) is present in dilute solutions. The measurements were made at 20 degrees C as functions of(a) the C(12)E(5) concentration at constant PEO concentration, (b) the PEO concentration at constant C(12)E(5) concentration, and (c) the C(12)E(5)/PEO concentration ratio. The influence of temperature on the interactions in terms of the relaxation time distributions was also examined up to the cloud point. It was found that when the C(12)E(5)/PEO weight ratio was >2 and when the temperature was >14 degrees C, the correlation functions became bimodal with well-separated components. The fast mode derives fi om individual surfactant micelles which are present in the solution at high number density. The appearance of the slow mode, which dominates the scattering, is interpreted as resulting from the formation of micellar clusters due to an excluded-volume effect when the high molar mass (M = 6 x 10(5)) PEO is added to the surfactant solution. It is shown that the micellar clusters form within the PEO coils and lead to a progressive swelling of the latter for steric reasons. The dimensions of the PEO/C(12)E(5) complex increase with increasing surfactant concentration to a value of R(H) approximate to 94 nm (R(g) approximate to 208 nm) at C-C12E5 = 3.5%. Fluorescence quenching measurements show that the average aggregation number of C(12)E(5) increases significantly on addition of the high molar mass PEG. With increasing temperature toward the cloud point the clusters increase in number density and/or become larger. The cloud point is substantially lower than that for C12E5 in water solution and is strongly dependent on the PEO concentration.

Interaction of the nonionic surfactant C12E8 with high molar mass poly(ethylene oxide) studied by dynamic light scattering and fluorescence quenching methods

Dynamic light scattering has been used to investigate ternary aqueous solutions of n-dodecyl octaoxyethylene glycol monoetber (C12E8) with high molar mass poly(ethylene oxide) (PEO). The measurements were made at 20 °C, always below the cloud point temperature (Tc) of the mixed solutions. The relaxation time distributions are bimodal at higher PEO and surfactant concentrations, owing to the preacute of free surfactant micelles, which coexist with the slower component, representing the polymer coil/micellar cluster comptex. As the surfactant concentration is increased, the apparent hydrodynamic radius (RH) of the coil becomes progressively larger. It is suggested that the complex structure consists of clusters of micelles sited within the polymer coil, as previously concluded for the PEO-C12E8-water system. However. C12E8 interacts less strongly than C12E8 with PEO; at low concentrations of surfactant the complex does not contribute significantly to the total scattered intensity. The perturbation of the PEO coil radius with C12E8 is also smaller than that in the C12E8 system. The addition of PEO strongly decreases the clouding temperature of the system, as previously observed for C12E8/PEO mixtures in solution Addition of PEO up to 0.2% to C12E8 (10 wt %) solutions doss not alter the aggregation number (Nagg) of the micelles probably because the surfactant monomers are equally partitioned as bound and unbound micelles. The critical micelle concentration (cmc), obtained from the I1/I3 ratio (a measure of the dependence of the vibronic band intensities on the pyrene probe environment), does not change when PEO is added, suggesting that for neutral polymer/surfactant systems the trends in Nagg and the cmc do not unambiguously reflect the strength of interaction.

Synthese und Charakterisierung von multivalenten kationischen Tensiden und Polymeren

Der Einsatz von den Polyelektrolytkomplexen von DNA / RNA mit Polykationen oder Lipiden in der Gen-Therapie ist für Wissenschaftler von besonderem Interesse, da sie als Träger für den Transport von genetischem Material in lebende Zellen fungieren können. Interessant ist auch die Komplexbildung aus Gadolinium und Polykation, hier können die stabil gebildeten Aggregate als Kontrastmittel zur Anwendung in der Magnetresonanztomographie eingeführt werden. Ziel der vorliegenden Arbeit war es, strukturdefinierte, positiv geladene, polyvalente sperminanaloge Polymere zu synthetisieren. Durch die polyelektrolytische Natur erlauben solche Polymere die Komplexierung von mehr Gadolinium-Polyoxometalaten und wären deshalb sehr gut als Kontrastmittel geeignet. Aufbauend auf den Vorarbeiten, wurde insbesondere die Komplexbildung von kationischem Polymer mit der Green Fluorescent Protein DNA in physiologischem Salzgehalt untersucht. Die Beschreibung der Synthese im Rahmen dieser Arbeit zeigt, dass es mit dem entwickelten Syntheseprinzip, also unter Einsatz von orthogonaler Schutzgruppenchemie und funktionaler Transformation gelungen ist, durch einfache nukleophile Substitution die Kopplung der Elementareinheiten zu komplexeren, auch ionischen Tensiden durchzuführen. Die Komplexierung von Gadolinium-Polyoxometalat mit kationisch geladenem Polymer in reinem Wasser und in physiologischem Salzgehalt hat gezeigt, dass bei einem Ladungsverhältnis von ungefähr 2:1 stabile sphärische Komplexe gebildet werden. HeLa-Zellen zeigen keine hohe Empfindlichkeit gegenüber Polykation-POM-Komplexen, da deren toxische Wirkung nur einen Anteil toter Zellen von maximal 24 % zur Folge hatte. Die Bildqualität einer MRT-Aufnahme der gebildeten Polykation-POM-Komplexe wurde im Vergleich zu den reinen Gadolinium-Polyoxometalat-Lösungen erheblich verbessert. Die Komplexierung von DNA mit dem im Überschuss vorliegenden kationisch geladenen Polymer wurde mittels Rasterkraftmikroskopie, statischer sowie dynamischer Lichtstreuung untersucht. Die Molmasse und Größe der Polykation-DNA-Komplexe geben eindeutige Hinweise darauf, dass sich in physiologischer Salzlösung Multi-Ketten-Komplexe bilden. Neben der Untersuchung der Polymer-Komplexe wurde eine Reihe neuartiger multivalenter kationischer Tenside hergestellt, wobei ihre Eigenschaften beispielsweise mit Tensid B (C12N4), Tensid C (EG8N4) und Tensid F (EG8C12N4) in wässriger Lösung bei verschiedener Salzkonzentration im Vordergrund stehen.

Category fluency test: effects of age, gender and education on total scores, clustering and switching in Brazilian Portuguese-speaking subjects

Verbal fluency tests are used as a measure of executive functions and language, and can also be used to evaluate semantic memory. We analyzed the influence of education, gender and age on scores in a verbal fluency test using the animal category, and on number of categories, clustering and switching. We examined 257 healthy participants (152 females and 105 males) with a mean age of 49.42 years (SD = 15.75) and having a mean educational level of 5.58 (SD = 4.25) years. We asked them to name as many animals as they could. Analysis of variance was performed to determine the effect of demographic variables. No significant effect of gender was observed for any of the measures. However, age seemed to influence the number of category changes, as expected for a sensitive frontal measure, after being controlled for the effect of education. Educational level had a statistically significant effect on all measures, except for clustering. Subject performance (mean number of animals named) according to schooling was: illiterates, 12.1; 1 to 4 years, 12.3; 5 to 8 years, 14.0; 9 to 11 years, 16.7, and more than 11 years, 17.8. We observed a decrease in performance in these five educational groups over time (more items recalled during the first 15 s, followed by a progressive reduction until the fourth interval). We conclude that education had the greatest effect on the category fluency test in this Brazilian sample. Therefore, we must take care in evaluating performance in lower educational subjects.

Graph analysis of verbal fluency test discriminate between patients with Alzheimer’s disease, Mild Cognitive Impairment and normal elderly controls

Verbal fluency is the ability to produce a satisfying sequence of spoken words during a given time interval. The core of verbal fluency lies in the capacity to manage the executive aspects of language. The standard scores of the semantic verbal fluency test are broadly used in the neuropsychological assessment of the elderly, and different analytical methods are likely to extract even more information from the data generated in this test. Graph theory, a mathematical approach to analyze relations between items, represents a promising tool to understand a variety of neuropsychological states. This study reports a graph analysis of data generated by the semantic verbal fluency test by cognitively healthy elderly (NC), patients with Mild Cognitive Impairment – subtypes amnestic(aMCI) and amnestic multiple domain (a+mdMCI) - and patients with Alzheimer’s disease (AD). Sequences of words were represented as a speech graph in which every word corresponded to a node and temporal links between words were represented by directed edges. To characterize the structure of the data we calculated 13 speech graph attributes (SGAs). The individuals were compared when divided in three (NC – MCI – AD) and four (NC – aMCI – a+mdMCI – AD) groups. When the three groups were compared, significant differences were found in the standard measure of correct words produced, and three SGA: diameter, average shortest path, and network density. SGA sorted the elderly groups with good specificity and sensitivity. When the four groups were compared, the groups differed significantly in network density, except between the two MCI subtypes and NC and aMCI. The diameter of the network and the average shortest path were significantly different between the NC and AD, and between aMCI and AD. SGA sorted the elderly in their groups with good specificity and sensitivity, performing better than the standard score of the task. These findings provide support for a new methodological frame to assess the strength of semantic memory through the verbal fluency task, with potential to amplify the predictive power of this test. Graph analysis is likely to become clinically relevant in neurology and psychiatry, and may be particularly useful for the differential diagnosis of the elderly.

Graph analysis of verbal fluency test discriminate between patients with Alzheimer’s disease, Mild Cognitive Impairment and normal elderly controls

Verbal fluency is the ability to produce a satisfying sequence of spoken words during a given time interval. The core of verbal fluency lies in the capacity to manage the executive aspects of language. The standard scores of the semantic verbal fluency test are broadly used in the neuropsychological assessment of the elderly, and different analytical methods are likely to extract even more information from the data generated in this test. Graph theory, a mathematical approach to analyze relations between items, represents a promising tool to understand a variety of neuropsychological states. This study reports a graph analysis of data generated by the semantic verbal fluency test by cognitively healthy elderly (NC), patients with Mild Cognitive Impairment – subtypes amnestic(aMCI) and amnestic multiple domain (a+mdMCI) - and patients with Alzheimer’s disease (AD). Sequences of words were represented as a speech graph in which every word corresponded to a node and temporal links between words were represented by directed edges. To characterize the structure of the data we calculated 13 speech graph attributes (SGAs). The individuals were compared when divided in three (NC – MCI – AD) and four (NC – aMCI – a+mdMCI – AD) groups. When the three groups were compared, significant differences were found in the standard measure of correct words produced, and three SGA: diameter, average shortest path, and network density. SGA sorted the elderly groups with good specificity and sensitivity. When the four groups were compared, the groups differed significantly in network density, except between the two MCI subtypes and NC and aMCI. The diameter of the network and the average shortest path were significantly different between the NC and AD, and between aMCI and AD. SGA sorted the elderly in their groups with good specificity and sensitivity, performing better than the standard score of the task. These findings provide support for a new methodological frame to assess the strength of semantic memory through the verbal fluency task, with potential to amplify the predictive power of this test. Graph analysis is likely to become clinically relevant in neurology and psychiatry, and may be particularly useful for the differential diagnosis of the elderly.

Graph analysis of verbal fluency test discriminate between patients with Alzheimer’s disease, Mild Cognitive Impairment and normal elderly controls

Verbal fluency is the ability to produce a satisfying sequence of spoken words during a given time interval. The core of verbal fluency lies in the capacity to manage the executive aspects of language. The standard scores of the semantic verbal fluency test are broadly used in the neuropsychological assessment of the elderly, and different analytical methods are likely to extract even more information from the data generated in this test. Graph theory, a mathematical approach to analyze relations between items, represents a promising tool to understand a variety of neuropsychological states. This study reports a graph analysis of data generated by the semantic verbal fluency test by cognitively healthy elderly (NC), patients with Mild Cognitive Impairment – subtypes amnestic(aMCI) and amnestic multiple domain (a+mdMCI) - and patients with Alzheimer’s disease (AD). Sequences of words were represented as a speech graph in which every word corresponded to a node and temporal links between words were represented by directed edges. To characterize the structure of the data we calculated 13 speech graph attributes (SGAs). The individuals were compared when divided in three (NC – MCI – AD) and four (NC – aMCI – a+mdMCI – AD) groups. When the three groups were compared, significant differences were found in the standard measure of correct words produced, and three SGA: diameter, average shortest path, and network density. SGA sorted the elderly groups with good specificity and sensitivity. When the four groups were compared, the groups differed significantly in network density, except between the two MCI subtypes and NC and aMCI. The diameter of the network and the average shortest path were significantly different between the NC and AD, and between aMCI and AD. SGA sorted the elderly in their groups with good specificity and sensitivity, performing better than the standard score of the task. These findings provide support for a new methodological frame to assess the strength of semantic memory through the verbal fluency task, with potential to amplify the predictive power of this test. Graph analysis is likely to become clinically relevant in neurology and psychiatry, and may be particularly useful for the differential diagnosis of the elderly.

Formation and characterization of soy bean oil/surfactant/water microemulsions

Pseudoternary phase diagrams, at 25 degrees C, were constructed for the systems soy bean oil (SBO)/surfactant/water, with single anionic sodium bis(2-ethylhexyl)sulfosuccinate (AOT), nonionic monoolein (MO) and mixtures of these surfactants, showing the isotropic phase of W/O microemulsions (MEs). The area of ME formation in the phase diagrams was shown to be dependent of the relative amount of surfactants, being larger for MO:AOT equals to 2:1. Rheological and dynamic light scattering (DLS) studies indicated that the viscosity of the isotropic ME phase exhibited two different behaviors depending on composition. The viscosity of dry MEs initially decreased with increasing amount of water following a dilution line in the phase diagram, i.e., a constant surfactant:SBO percentage ratio. As the water content increased the relative viscosity attained a minimum and then increased. This minimum could be related to the transition between two ME regions, L-2 and L'(2), having different characteristics. DLS measurements confirm the existence of ordinary W/O ME droplets in the L-2 region and suggest the existence of another structure in the L'(2) region. The size of the MEs droplets in L-2 phase ranges from 3.6 to 16.5 nm, depending on composition of SBO, surfactant and water. Small angle X-ray scattering (SAXS) also indicates the existence of structures with different characteristics, for the SAXS curves exhibit a typical micelle asymmetrical peak at low scattering vector q for MEs in L-2 but a symmetrical correlation peak at higher q vector in L'(2). (c) 2006 Elsevier B.V. All rights reserved.

FaSSIF-C, a Cholesterol containing biorelevant intestinal model medium for development and test of oral drug formulations

Biorelevante Medien sind entwickelt worden, um die Bedingungen im Magen-Darm-Trakt vor und nach der Mahlzeit zu imitieren. Mit FaSSIF und FeSSIF wurden Medien eingeführt, die nicht nur die pH- und Puffer-Kapazität des Dünndarms widerspiegeln, sondern auch Lipid und physiologische Tensid-Arten enthalten. Diese Medien (FaSSIF-V2 und FaSSlFmod6.5) wurden für Bioverfügbarkeitstudien in der Medikamentenentwicklung im Laufe der Jahre kontinuierlich weiterentwickelt. Dennoch sind die auf dem Markt verfügbaren Medien immer noch nicht in der Lage, die realen physiologischen Bedingungen zu simulieren. In der jetzigen Zusammensetzung sind nicht alle Kompetenten enthalten, welche natürlicher Weise im Duodenum vorkommen. Darüber hinaus wird nur eine 1:5 Verdünnung von FeSSIF zu FaSSIF angenommen, die individuelle Wasserzufuhr bei Medikamentengabe wird hierdurch jedoch nur eingeschränkt simuliert, obwohl diese von Patient zu Patient schwanken kann. rnZiel dieser Dissertation war die Verbesserung der Vorhersage der Auflösung und Absorption lipophiler Arzneistoffe durch Simulation der Bedingungen im zweiten Teil des Zwölffingerdarms mit neuen biorelevanten Medien, sowie unter Einwirkung zusätzlicher Detergention als Wirkstoffträger. rnUm den Effekt der Verdünnungsrate und Zeit im Dünndarm zu untersuchen, wurde die Entwicklung der Nanopartikel in der Magen-Darm-Flüssigkeit FaSSIFmod6.5 zu verschiedenen Zeitpunkten und Wassergehalten untersucht. Dafür wurden kinetische Studien an verschieden konzentrierten Modellmedien nach Verdünnungssprung untersucht. Das Modell entspricht der Vermischung der Gallenflüssigkeit mit dem Darminhalt bei variablem Volumen. Die Ergebnisse zeigen, dass Art und Größe der Nanopartikel stark von Verdünnung und Einirkungszeit abhängen. rnrnDie menschliche Darmflüssigkeit enthält Cholesterin, welches in allen früheren Modellmedien fehlt. Daher wurden biokompatible und physiologische Modellflüssigkeiten, FaSSIF-C, entwickelt. Der Cholesteringehalt von FaSSIF - 7C entspricht der Gallenflüssigkeit einer gesunden Frau, FaSSIF - 10C der einer gesunden männlichen Person und FaSSIF - 13C der in einigen Krankheitszuständen. Die intestinale Teilchen-Struktur-Untersuchung mit dynamische Lichtstreuung (DLS) und Neutronen-Kleinwinkelstreuung (SANS) ergab, dass die Korngröße von Vesikeln mit zunehmender Cholesterin-Konzentration abnahm. Zu hohe Cholesterin-Konzentration bewirkte zusätzlich sehr große Partikel, welche vermutlich aus Cholesterin-reichen “Disks“ bestehen. Die Löslichkeiten einiger BCS Klasse II Wirkstoffe (Fenofibrat, Griseofulvin, Carbamazepin, Danazol) in diesen neuen Medien zeigten, dass die Löslichkeit in unterschiedlicher Weise mit der Cholesteringehalt zusammen hing und dieser Effekt selektiv für die Droge war. rnDarüber hinaus wurde die Wirkung von einigen Tensiden auf die kolloidale Struktur und Löslichkeit von Fenofibrat in FaSSIFmod6.5 und FaSSIF -7C untersucht. Struktur und Löslichkeit waren Tensid- und Konzentrations-abhängig. Im Falle von FaSSIFmod6.5 zeigten die Ergebnisse eine dreifache Verzweigung der Lösungswege. Im Bereich mittlerer Tensidkonzentration wurde eine Löslichkeitslücke der Droge zwischen der Zerstörung der Galle-Liposomen und der Bildung von Tensid-reichen Mizellen beobachtet. In FaSSIF - 7C, zerstörten Tenside in höherer Konzentration die Liposomenstruktur trotz der allgemeinen Stabilisierung der Membranen durch Cholesterin. rnDie in dieser Arbeit vorgestellten Ergebnisse ergeben, dass die Anwesenheit von Cholesterin als eine fehlende Komponente der menschlichen Darmflüssigkeit in biorelevanten Medien wichtig ist und dazu beitragen kann, das in vivo Verhalten schwerlöslicher Arzneistoffe im Körper besser vorhersagen zu können. Der Verdünnungsgrad hat einen Einfluss auf die Nanopartikel-Struktur und Tenside beeinflussen die Löslichkeit von Medikamenten in biorelevanten Medien: Dieser Effekt ist sowohl von der Konzentration das Tensids abhängig, als auch dessen Typ.rnrn

Préparations de docosanol nanoformulées pour usage topique

La réduction de la taille des particules jusqu’à l’obtention de nanocristaux est l’une des approches utilisées afin d’améliorer la pénétration cutanée des médicaments à usage topique. Nous proposons que la fabrication d’une formulation semi solide (hydrogel) à base de nanosuspension de docosanol, aboutira à une diffusion du principe actif supérieure à celle du produit commercial Abreva®, à travers des membranes synthétiques de polycarbonates. Le broyage humide est la technique proposée pour la production des nanoparticules de docosanol. Nous proposons aussi la préparation d’une formulation semi-solide (hydrogel) à usage topique à partir de la nanosuspension de docosanol. La nanosuspension de docosanol est obtenue par dispersion du docosanol en solution aqueuse en présence du polymère stabilisant hydroxypropylcellulose (HPC) et du surfactant laurylsulfate de sodium (SDS) suivi d’un broyage humide à faible ou à haute énergie. L’hydrogel de docosanol nanoformulé est préparé à l’aide de la nanosuspension de docosanol qui subit une gélification par le carbopol Ultrez 21 sous agitation mécanique suivie d’une neutralisation au triéthanolamine TEA. La taille des particules de la nanosuspension et de l’hydrogel a été déterminée par diffusion dynamique de la lumière (DLS). Une méthode analytique de chromatographie liquide à haute performance (HPLC) munie d’un détecteur évaporatif (ELSD) a été développée et validée pour évaluer la teneur de docosanol dans les préparations liquides, dans les différentes nanosuspensions et dans les hydrogels de docosanol. L’état de cristallinité des nanocristaux dans la nanosuspension et dans l’hydrogel a été étudié par calorimétrie différentielle à balayage. La morphologie de la nanosuspension et de l’hydrogel de docosanol a été examinée par microscopie électronique à balayage (MEB). Les propriétés rhéologiques et de stabilité physique à différentes températures ont été aussi étudiées pour la formulation semi-solide (hydrogel). De même, la libération in vitro du docosanol contenu dans l’hydrogel et dans le produit commercial Abreva® a été étudiée à travers deux membranes de polycarbonates de taille de pores 400 et 800 nm. Dans le cas de nanosuspensions, des cristaux de docosanol de taille nanométrique ont été produits avec succès par broyage humide. Les nanoparticules de tailles variant de 197 nm à 312 nm ont été produites pour des pourcentages différents en docosanol, en polymère HPC et en surfactant SDS. Après lyophilisation, une augmentation de la taille dépendant de la composition de la formulation a été observée tout en restant dans la gamme nanométrique pour la totalité presque des formulations étudiées. Dans le cas des hydrogels examinés, la taille moyenne des particules de docosanol est maintenue dans la gamme nanométrique avant et après lyophilisation. L’analyse thermique des mélanges physiques, des nanosuspensions et des hydrogels de docosanol a révélé la conservation de l’état de cristallinité des nanocristaux de docosanol après broyage et aussi après gélification. L’examen par microscopie électronique à balayage (MEB) a montré que la nanosuspension et l’hydrogel ont tous deux une morphologie régulière et les nanoparticules ont une forme sphérique. De plus les nanoparticules de la nanosuspension ont presque la même taille inférieure à 300 nm en accord avec le résultat obtenu par diffusion dynamique de la lumière (DLS). Les nanoparticules de l’hydrogel ont une légère augmentation de taille par rapport à celle de la nanosuspension, ce qui est en accord avec les mesures de DLS. D’après les mesures rhéologiques, l’hydrogel de docosanol a un comportement pseudoplastique et un faible degré de thixotropie. L’étude de stabilité physique a montré que les formulations d’hydrogel sont stables à basse température (5°C) et à température ambiante (21°C) pendant une période d’incubation de 13 semaines et instable au-delà de 30°C après deux semaines. La méthode HPLC-ELSD a révélé des teneurs en docosanol comprises entre 90% et 110% dans le cas des nanosuspensions et aux alentours de 100% dans le cas de l’hydrogel. L’essai de diffusion in vitro a montré qu’il y a diffusion de docosanol de l’hydrogel à travers les membranes de polycarbonates, qui est plus marquée pour celle de pore 800 nm, tandis que celui du produit commercial Abreva® ne diffuse pas. Le broyage humide est une technique bien adaptée pour la préparation des nanosuspensions docosanol. Ces nanosuspensions peuvent être utilisée comme base pour la préparation de l’hydrogel de docosanol nanoformulé.

Structure, rheology and shear alignment of Pluronic block copolymer mixtures

The structure and flow behaviour of binary mixtures of Pluronic block copolymers P85 and P123 is investigated by small-angle scattering, rheometry and mobility tests. Micelle dimensions are probed by dynamic light scattering. The micelle hydrodynamic radius for the 50/50 mixture is larger than that for either P85 or P123 alone, Clue to the formation of mixed micelles with a higher association number. The phase diagram for 50/50 mixtures contains regions Of Cubic and hexagonal phases similar to those for the parent homopolymers, however the region of stability of the cubic phase is enhanced at low temperature and concentrations above 40 wt%. This is ascribed to favourable packing of the mixed micelles containing core blocks with two different chain lengths, but similar corona chain lengths. The shear flow alignment of face-centred cubic and hexagonal phases is probed by in situ small-angle X-ray or neutron scattering with simultaneous rheology. The hexagonal phase can be aligned using steady shear in a Couette geometry, however the high modulus Cubic phase cannot be aligned well in this way. This requires the application of oscillatory shear or compression. (C) 2008 Elsevier Inc. All rights reserved.

Polymer − surfactant vesicular complexes in aqueous medium

The introduction of ionic single-tailed surfactants to aqueous solutions of EO18BO10 [EO = poly(ethylene oxide), BO = poly(1,2-butylene oxide), subscripts denote the number of repeating units] leads to the formation of vesicles, as probed by laser scanning confocal microscopy. Dynamic light scattering showed that the dimensions of these aggregates at early stages of development do not depend on the sign of the surfactant head group charge. Small-angle X-ray scattering (SAXS) analysis indicated the coexistence of smaller micelles of different sizes and varying polymer content in solution. In strong contrast to the dramatic increase of size of dispersed particles induced by surfactants in dilute solution, the d-spacing of corresponding mesophases reduces monotonically upon increasing surfactant loading. This effect points to the suppression of vesicles as a consequence of increasing ionic strength in concentrated solutions. Maximum enhancements of storage modulus and thermal stability of hybrid gels take place at different compositions, indicating a delicate balance between the number and size of polymer-poor aggregates (population increases with surfactant loading) and the number and size of polymer−surfactant complexes (number and size decrease in high surfactant concentrations).