Conditional equilibrium constants in multicomponent heterogeneous adsorption: The conditional affinity spectrum

The concept of conditional stability constant is extended to the competitive binding of small molecules to heterogeneous surfaces or macromolecules via the introduction of the conditional affinity spectrum (CAS). The CAS describes the distribution of effective binding energies experienced by one complexing agent at a fixed concentration of the rest. We show that, when the multicomponent system can be described in terms of an underlying affinity spectrum [integral equation (IE) approach], the system can always be characterized by means of a CAS. The thermodynamic properties of the CAS and its dependence on the concentration of the rest of components are discussed. In the context of metal/proton competition, analytical expressions for the mean (conditional average affinity) and the variance (conditional heterogeneity) of the CAS as functions of pH are reported and their physical interpretation discussed. Furthermore, we show that the dependence of the CAS variance on pH allows for the analytical determination of the correlation coefficient between the binding energies of the metal and the proton. Nonideal competitive adsorption isotherm and Frumkin isotherms are used to illustrate the results of this work. Finally, the possibility of using CAS when the IE approach does not apply (for instance, when multidentate binding is present) is explored. © 2006 American Institute of Physics.

Poly(beta,L-malic acid)Doxorubicin ionic complex: A pH-dependent delivery system.

Poly(ß,L-malic acid) (PMLA) was made to interact with the cationic anticancer drug Doxorubicin (DOX) in aqueous solution to form ionic complexes with different compositions and an efficiency near to 100%. The PMLA/DOX complexes were characterized by spectroscopy, thermal analysis, and scanning electron microscopy. According to their composition, the PMLA/DOX complexes spontaneously self-assembled into spherical micro or nanoparticles with negative surface charge. Hydrolytic degradation of PMLA/DOX complexes took place by cleavage of the main chain ester bond and simultaneous release of the drug. In vitro drug release studies revealed that DOX delivery from the complexes was favored by acidic pH and high ionic strength

The role of counterions in the membrane-disruptive properties of pH-sensitive lysine-based surfactants

Surfactants are among the most versatile and widely used excipients in pharmaceuticals. This versatility, together with their pH-responsive membrane-disruptive activity and low toxicity, could also enable their potential application in drug delivery systems. Five anionic lysine-based surfactants which differ in the nature of their counterion were studied. Their capacity to disrupt the cell membrane was examined under a range of pH values, concentrations and incubation times, using a standard hemolysis assay as a model for endosomal membranes. The surfactants showed pH-sensitive hemolytic activity and improved kinetics at the endosomal pH range. Low concentrations resulted in negligible hemolysis at physiological pH and high membrane lytic activity at pH 5.4, which is in the range characteristic of late endosomes. With increasing concentration, the surfactants showed an enhanced capacity to lyse cell membranes, and also caused significant membrane disruption at physiological pH. This observation indicates that, at high concentrations, surfactant behavior is independent of pH. The mechanism of surfactant-mediated membrane destabilization was addressed, and scanning electron microscopy studies were also performed to evaluate the effects of the compounds on erythrocyte morphology as a function of pH. The in vitro cytotoxicity of the surfactants was assessed by MTT and NRU assays with the 3T3 cell line. The influence of different types of counterion on hemolytic activity and the potential applications of these surfactants in drug delivery are discussed. The possibility of using pH-sensitive surfactants for endosome disruption could hold great promise for intracellular drug delivery systems in future therapeutic applications.

Phospholipid bilayer perturbing-properties underlying lysis induced by pH-sensitive cationic lysine-based surfactants in biomembranes

Many strategies for treating diseases require the delivery of drugs into the cell cytoplasm following internalization within endosomal vesicles. Thus, compounds triggered by low pH to disrupt membranes and release endosomal contents into the cytosol are of particular interest. Here, we report novel cationic lysine-based surfactants (hydrochloride salts of Nε- and Nα-acyl lysine methyl ester) that differ in the position of the positive charge and the length of the alkyl chain. Amino acid-based surfactants could be promising novel biomaterials in drug delivery systems, given their biocompatible properties and low cytotoxic potential. We examined their ability to disrupt the cell membrane in a range of pH values, concentrations and incubation times, using a standard hemolysis assay as a model of endosomal membranes. Furthermore, we addressed the mechanism of surfactant-mediated membrane destabilization, including the effects of each surfactant on erythrocyte morphology as a function of pH. We found that only surfactants with the positive charge on the α-amino group of lysine showed pH-sensitive hemolytic activity and improved kinetics within the endosomal pH range, indicating that the positive charge position is critical for pH-responsive behavior. Moreover, our results showed that an increase in the alkyl chain length from 14 to 16 carbon atoms was associated with a lower ability to disrupt cell membranes. Knowledge on modulating surfactant-lipid bilayer interactions may help us to develop more efficient biocompatible amino acid-based drug delivery devices.

Análisis de una experiencia de aprendizaje basado en proyectos en la asignatura de Fundamentos de Física = Project based learning: analysis of an experience in Introductory Physics courses

In this work we present and analyze the application of an experience of Project Based Learning (PBL) in the matter of Physics II of the Industrial Design university degree (Girona University) during 2005-2006 courses. This methodology was applied to the Electrostatic and Direct Current subjects. Furthermore, evaluation and self evaluation results were shown and the academic results were compared with results obtained in the same subjects applying conventional teaching methods

Molecular Physics of Elementary Processes relevant to Hypersonics: atom-molecule, molecule-molecule and atom-surface processes.

In the present chapter some prototype gas and gas-surface processes occurring within the hypersonic flow layer surrounding spacecrafts at planetary entry are discussed. The discussion is based on microscopic dynamical calculations of the detailed cross sections and rate coefficients performed using classical mechanics treatments for atoms, molecules and surfaces. Such treatment allows the evaluation of the efficiency of thermal processes (both at equilibrium and nonequilibrium distributions) based on state-to-state and state specific calculations properly averaged over the population of the initial states. The dependence of the efficiency of the considered processes on the initial partitioning of energy among the various degrees of freedom is discussed.

Valors típics de pH i DP del suport de tela en la pintura de cavallet

Ja fa varies decades que els conservadors-restauradors de paper van comenc;ar a tenir en compteel pH de les obres que tractaven, ja que es va veure que I'acidesa incidia molt directament en comde rapid I'objecte es debilitava mecimicament. De fet, trobem tant aviat com el 1936, una patenten registrada per OJ. Schierholtz per desacidificar el paper d'empaperar parets (Porck, 1996).La tela d'un quadre, essent un teixit fet a base de fibres vegetals compastes majoritariament perceHulosa, com les fibres del paper, és lógicament també facilment degradable si I'ambient ñes acid(te un baix pH).Sorprenentment, pero, I'acidesa de la tela deis quadres, tot i que en ocasions puntuals ha estatanalitzada (Bajocchi, 2009; Young, 1999), encara no és un parametre que es miri de forma rutinariai per tant, fins recentment, no se sabia quins eren els valors de pH més típics que pot tenir unquadre.Aquest estudi és una primera recopilació sistematica d'aquest t ipus d' in formació per a partir d'aquícrear un banc de dades que vagi recollint aquest t ipus d'informació sobre el majar nombre possiblede quadres.Si I'acidesa present en la tela ens indica com de rapid es degradara aquesta en el futur, la mesura delgrau de polimerització de la tela (DP), ens indica si la tela té una al ta o baixa resistencia mecanica enel moment actual. Així doncs, aquests dos parametres ens aporten informació molt úti l sobre I'estatde conserva ció del suportoAquesta recerca pretén respondre a les preguntes de quins són els valors de pH i DP que típicamentpodem trabar en la tela deis quadres, així com analitzar la relació entre aquests dos parametres i també la relació entre la data de producció deis quadres i els valors de pH i DP.

Valors típics de pH i DP del suport de tela en la pintura de cavallet

Ja fa varies decades que els conservadors-restauradors de paper van comenc;ar a tenir en compteel pH de les obres que tractaven, ja que es va veure que I'acidesa incidia molt directament en comde rapid I'objecte es debilitava mecimicament. De fet, trobem tant aviat com el 1936, una patenten registrada per OJ. Schierholtz per desacidificar el paper d'empaperar parets (Porck, 1996).La tela d'un quadre, essent un teixit fet a base de fibres vegetals compastes majoritariament perceHulosa, com les fibres del paper, és lógicament també facilment degradable si I'ambient ñes acid(te un baix pH).Sorprenentment, pero, I'acidesa de la tela deis quadres, tot i que en ocasions puntuals ha estatanalitzada (Bajocchi, 2009; Young, 1999), encara no és un parametre que es miri de forma rutinariai per tant, fins recentment, no se sabia quins eren els valors de pH més típics que pot tenir unquadre.Aquest estudi és una primera recopilació sistematica d'aquest t ipus d' in formació per a partir d'aquícrear un banc de dades que vagi recollint aquest t ipus d'informació sobre el majar nombre possiblede quadres.Si I'acidesa present en la tela ens indica com de rapid es degradara aquesta en el futur, la mesura delgrau de polimerització de la tela (DP), ens indica si la tela té una al ta o baixa resistencia mecanica enel moment actual. Així doncs, aquests dos parametres ens aporten informació molt úti l sobre I'estatde conserva ció del suportoAquesta recerca pretén respondre a les preguntes de quins són els valors de pH i DP que típicamentpodem trabar en la tela deis quadres, així com analitzar la relació entre aquests dos parametres i també la relació entre la data de producció deis quadres i els valors de pH i DP.