Combination of light-driven co-delivery of chemodrugs and plasmonic-induced heat for cancer therapeutics using hybrid protein nanocapsules.

BACKGROUND: Improving the water solubility of hydrophobic drugs, increasing their accumulation in tumor tissue and allowing their simultaneous action by different pathways are essential issues for a successful chemotherapeutic activity in cancer treatment. Considering potential clinical application in the future, it will be promising to achieve such purposes by developing new biocompatible hybrid nanocarriers with multimodal therapeutic activity. RESULTS: We designed and characterised a hybrid nanocarrier based on human serum albumin/chitosan nanoparticles (HSA/chitosan NPs) able to encapsulate free docetaxel (DTX) and doxorubicin-modified gold nanorods (DOXO-GNRs) to simultaneously exploit the complementary chemotherapeutic activities of both antineoplasic compounds together with the plasmonic optical properties of the embedded GNRs for plasmonic-based photothermal therapy (PPTT). DOXO was assembled onto GNR surfaces following a layer-by-layer (LbL) coating strategy, which allowed to partially control its release quasi-independently release regarding DTX under the use of near infrared (NIR)-light laser stimulation of GNRs. In vitro cytotoxicity experiments using triple negative breast MDA-MB-231 cancer cells showed that the developed dual drug encapsulation approach produces a strong synergistic toxic effect to tumoral cells compared to the administration of the combined free drugs; additionally, PPTT enhances the cytostatic efficacy allowing cell toxicities close to 90% after a single low irradiation dose and keeping apoptosis as the main cell death mechanism. CONCLUSIONS: This work demonstrates that by means of a rational design, a single hybrid nanoconstruct can simultaneously supply complementary therapeutic strategies to treat tumors and, in particular, metastatic breast cancers with good results making use of its stimuli-responsiveness as well as its inherent physico-chemical properties.

NIR-light active hybrid nanoparticles for combined imaging and bimodal therapy of cancerous cells.

We report the synthesis of a multifunctional biocompatible theranostic nanoplatform consisting of a biodegradable PLGA matrix surface-functionalized with indocyanine green (ICG), a near-IR fluorescent dye, and co-loaded with superparamagnetic iron oxide nanoparticles (SPIONs) and the anticancer drug doxorubicin (DOXO). Combination of chemo- and photothermal therapeutic efficacy as well as magnetic resonance and optical fluorescence imaging performance were successfully tested in vitro on a tumoral cervical HeLa cell line. Magnetic in vitro guided targeting of these nanoplatforms was also proven. These nanoconstructs also enabled to monitor their in vivo biodistribution by fluorescence imaging in a mice model, which revealed their effective accumulation in the tumor and, unexpectedly, in the brain area. A lower presence of nanoplatforms was noted in the reticulo-endothelial system. The present observations suggest the nanoplatforms ability to possibly overcome the blood brain barrier. These results open up new possibilities to use our multifunctional nanoplatforms to treat brain-located diseases.

Cytocompatibility and P-glycoprotein inhibition of block copolymers: structure-activity relationship.

Amphiphilic polymeric micelles greatly improve the solubilization and sustained release of hydrophobic drugs and provide a protective environment for the cargo molecules in aqueous media, which favors lower drug administration doses, reduces adverse side effects, and increases blood circulation times and passive targeting to specific cells. These capabilities depend, among other variables, on the structure and composition of the polymer chains. Composition and, in particular, block length have been shown to play an important role in the modification of cellular responses such as drug internalization processes or transduction pathways when polymeric unimer/micelles are in close contact with cells. Here we present a detailed study about the role copolymer structure and composition play on cell viability and cellular response of several cell lines. To do that, more than 30 structurally related copolymers with diblock and triblock architectures containing different hydrophobic blocks and poly(ethylene oxide) as the common hydrophilic unit have been analyzed regarding cytocompatibility and potential as "active" cell response modifiers by testing their influence on the P-gp pump efflux mechanism responsible of multidrug resistance in cancerous cells. An empirical threshold for cell viability could be established at a copolymer EO/POeffective value above ca. 1.5 for copolymers with triblock structure, whereas no empirical rule could be observed for diblocks. Moreover, some of the tested copolymers (e.g., BO12EO227BO12 and EO57PO46EO57 that notably increased and C16EO455C16 that decreased the P-gp ATPase activity) were observed to act as efficient inhibitors of the P-gp efflux pump promoting an enhanced doxorubicin (DOXO) accumulation inside multidrug resistant (MDR) NCI-ADR-RES cells.

Doxorubicin-loaded micelles of reverse poly(butylene oxide)-poly(ethylene oxide)-poly(butylene oxide) block copolymers as efficient "active" chemotherapeutic agents.

Five reverse poly(butylene oxide)-poly(ethylene oxide)-poly(butylene oxide) block copolymers, BOnEOmBOn, with BO ranging from 8 to 21 units and EO from 90 to 411 were synthesized and evaluated as efficient chemotherapeutic drug delivery nanocarriers and inhibitors of the P-glycoprotein (P-gp) efflux pump in a multidrug resistant (MDR) cell line. The copolymers were obtained by reverse polymerization of poly(butylene oxide), which avoids transfer reaction and widening of the EO block distribution, commonly found in commercial poly(ethylene oxide)-poly(propylene oxide) block copolymers (poloxamers). BOnEOmBOn copolymers formed spherical micelles of 10-40 nm diameter at lower concentrations (one order of magnitude) than those of equivalent poloxamers. The influence of copolymer block lengths and BO/EO ratios on the solubilization capacity and protective environment for doxorubicin (DOXO) was investigated. Micelles showed drug loading capacity ranging from ca. 0.04% to 1.5%, more than 150 times the aqueous solubility of DOXO, and protected the cargo from hydrolysis for more than a month due to their greater colloidal stability in solution. Drug release profiles at various pHs, and the cytocompatibility and cytotoxicity of the DOXO-loaded micelles were assessed in vitro. DOXO loaded in the polymeric micelles accumulated more slowly inside the cells than free DOXO due to its sustained release. All copolymers were found to be cytocompatible, with viability extents larger than 95%. In addition, the cytotoxicity of DOXO-loaded micelles was higher than that observed for free drug solutions in a MDR ovarian NCI-ADR-RES cell line which overexpressed P-gp. The inhibition of the P-gp efflux pump by some BOnEOmBOn copolymers, similar to that measured for the common P-gp inhibitor verapamil, favored the retention of DOXO inside the cell increasing its cytotoxic activity. Therefore, poly(butylene oxide)-poly(ethylene oxide) block copolymers offer interesting features as cell response modifiers to complement their role as efficient nanocarriers for cancer chemotherapy.

Poly(styrene oxide)-poly(ethylene oxide) block copolymers: From "classical" chemotherapeutic nanocarriers to active cell-response inducers.

Two poly(styrene oxide)-poly(ethylene oxide) (PSO-PEO) triblock copolymers with different chain lengths were analyzed as potential chemotherapeutic nanocarriers, and their ability to inhibit the P-glycoprotein (P-gp) efflux pump in a multidrug resistant (MDR) cell line were measured in order to establish possible cell-responses induced by the presence of the copolymer molecules. Thus, EO33SO14EO33 and EO38SO10EO38 polymeric micelles were tested regarding doxorubicin (DOXO) entrapment efficiency (solubilization test), physical stability (DLS), cytocompatibility (fibroblasts), release profiles at various pHs (in vitro tests), as well as P-gp inhibition and evasion and cytotoxicity of the DOXO-loaded micelles in an ovarian MDR NCI-ADR/RES cell line and in DOXO-sensitive MCF-7 cells. EO33SO14EO33 and EO38SO10EO38 formed spherical micelles (~13nm) at lower concentration than other copolymers under clinical evaluation (e.g. Pluronic®), exhibited 0.2% to 1.8% loading capacity, enhancing more than 60 times drug apparent solubility, and retained the cargo for long time. The copolymer unimers inhibited P-gp ATPase activity in a similar way as Pluronic P85, favoring DOXO accumulation in the resistant cell line, but not in the sensitive cell line. DOXO loaded in the micelles accumulated more slowly inside the cells, but caused greater cytotoxicity than free drug solutions in the NCI-ADR-RES cell line, which overexpressed P-gp. Hence, PSO-PEO block copolymers offer interesting features as new biological response modifiers to be used in the design of efficient nanocarriers for cancer chemotherapy.

Estrés en dos cohortes de estudiantes de medicina de la Escuela Luis Razetti-Universidad Central de Venezuela / Stress in two cohorts of medical students from the Escuela Luis Razetti-Universidad Central de Venezuela

El estrés es un proceso de interacción entre eventos del entorno biopsicosocial. Los síntomas relacionados con este, en estudiantes de medicina, puede variar a lo largo de su carrera. Se comparó la prevalencia de estrés en estudiantes de 1º a 5º año, con el objetivo de establacer si existen diferencias significativas entre ellos. La presente fue una investigación de corte transversal observacional, no experimental. El universo fue de 481 individuos (cohortes 2009-2010). En mayo 2010 se tomó una muestra probabilística, aleatoria simple, estratificada, de 116 estudiantes de 1º año y 88 de 5º año de la Escuela Luis Razetti (total 204,42% del universo). El instrumento de evaluación fue una encuesta que constaba de datos generales, Escala de Depresión, Ansiedad y Estrés (EDAS-21) y Estratificación Social de Graffar-Méndez-Castellano. Se utilizó el programa SPSS v.10.0 para el análisis de datos, nivel de confianza 95%. Respecto a la puntuación total del EDAS-21, delos estudiantes evaluados, 64,8% presentaron estrés normal y 6,7% estrés muy severo. La prevalencia de estrés de leve a muy severo en estudiantes de 1º fue significativamente mayor que de la de los de 5º año (42,7% vs. 27,8%; P<0,05). Se encontraron diferencias significativas en la frecuencia de estrés entre los estudiantes de 1º y 5º año, siendo mayor en los de 1º; lo cual puede deberse, dentro de otros factores, a la adaptación ante situaciones que generan estrés en los mismos a lo largp de su carrera

stress is considered as an interactive process between biopsychosocial events, symptoms related to it, in medical students, may vary along their careers. Stress prevalence was compared between 1º and 5º year students, to establish if significant differences exist or not. This was a cross-sectional, observational, non-experimental research. The universe was 481 individuals (cohort 2009-2010). In may 2010 a probabilistic, simple random, stratified sample of 116 students of 1º year and 88 of 5º at the School Luis Razetti was taken (total 204,42% of the universe). The evaluation instrument was a survey form consisting on general information, Depression, Anxiety and Stress Scale (DASS-21) and the Graffar-Méndez-Castellano Social Stratification. The Software SPSS v.10.0, with a 95% confidence level, was used for data analyses. Regarding the total DASS-21 score, from the evaluated students, 64.8% presented normal stress levels and 6.7% very severe stress levels. The Low to very severe stress levels prevalence in 1st year students was significantly higher than that presented in 5th year students (42.7% vs. 27,8%; P<0.05). Significant differences on stress frequency were evidenced between 1º and 5º year students, being higher in 1º year students; wich can be due, among other factors, to the adaptacion, ocurred along the years, to situacions that generate stress on their careers

Desarrollo y conducta adaptativa en niños con insuficiencia renal crónica en DPCA / Development and adaptative behavior in children with chronic renal insuffiency on CAPD

Los niños con enfermedad renal crónica encuentran un riesgo aumentado de presentar compromiso de su neurodesarrollo. El objetivo de este trabajo fue la evaluación cognitiva y adaptativa de 15 niños con insuficiencia renal crónica en tratamiento de reemplazo con diálisis peritoneal ambulatoria. El desarrollo cognitivo fue normal o superior en 3 pacientes (20%) y retrasado en 12 (80%). La conducta adaptativa fue adecuada en 8 (53%) y baja o muy baja en 7 (47%). No hubo relación entre el desarrollo cognitivo y la escolaridad materna o el nivel socio económico, ni entre la conducta adaptativa y el nivel de escolaridad materna. La relación entre el NSE y la conducta adaptativa fue significativa (p 0.04). Esto sugeriría que si bien la enfermedad renal crónica compromete el desarrollo cognitivo, un nivel socioeconómico medio/alto puede proveer oportunidades para una mejor conducta adaptativa.

Children with chronic kidney disease are at increased riskof having impaired neurodevelopment. The objective of thepresent study was to perform a cognitive and adaptive eva-luation of 15 children with chronic renal insufficiency onoutpatient peritoneal dialysis. Cognitive development wasnormal or above normal in 3 patients (20%) and delayed in12 (80%). Adaptive behavior was adequate in 8 (53%) andlow or very low in 7 (47%). No correlation was found eitherbetween cognitive development and maternal education orsocio-economic level or between adaptive behavior andeducation of the mother. A significant correlation was foundbetween socio-economic level and adaptive behavior (p0.04). This would suggest that although chronic kidney dise-ase compromises cognitive development, middle or uppersocio-economic level may provide opportunities for impro-ved adaptive behavior.

Conversion of heart transplant patients from standard to sustained-release tacrolimus requires a dosage increase.

INTRODUCTION: It has been suggested that for adequate maintenance of tacrolimus levels, the total daily dosage should be increased when switching from the conventional twice-daily regimen tacrolimus (CT) to once-daily sustained-release tacrolimus (SR-T). OBJECTIVE: To evaluate the safety and efficacy of a 25% increase in daily dosage when switching heart transplant (HT) patients from CT to SR-T. METHODS: We switched 75 HT patients including 72% males and an overall mean age of 55.6 years from CT to SR-T using a 25% increase in daily dosage. We screened for adverse events by measurements of lipids, creatinine, glycemia, and tacrolimus in blood samples taken at 1, 3, 7, and 12 weeks after the conversion, as well as by repeated echocardiography and routine clinical examinations. RESULTS: Just two patients (2.7%) were returned to CT because of failure of SR-T to attain therapeutic levels. In the remainder of subjects, tacrolimus levels remained stable, with trough values of 8.7±3.2, 8.7±2.9, 8.3±2.6, and 7.5±2.0 mg/dL, respectively. Twenty-three patients (31%) required no dosage change in the first 3 months, but 44 (33%) required one or two changes. No departure from therapeutic levels was associated with rejection; there was no case of severe intercurrent infection. We did not observe significant changes in glycemia, creatinine, lipid profile, or blood pressure. CONCLUSIONS: Administration of SR-T at a dosage 25% higher than the daily dosage of CT was safe. It ensured adequate tacrolimus levels in one-third of patients. Nevertheless, strict analytical surveillance is necessary during the initial months to allow dosage adjustments and to detect the minority of patients for whom SR-T does not achieve therapeutic tacrolimus levels.

Liofilización de pitahaya amarilla (Selenicereus megalanthus) / Freeze-drying in yellow pitahaya (Selenicereus megalanthus)

La liofilización es una alternativa de interés como método de conservación de alimentos, la cual permite prolongar el tiempo de vida útil manteniendo significativamente las propiedades físicas y fisicoquímicas relacionadas con su calidad. El objetivo de este trabajo fue evaluar el efecto de la liofilización y la osmoliofilización sobre las cinéticas de congelación y de secado, la actividad de agua, el volumen, la porosidad y la capacidad de rehidratación en rodajas de pitahaya amarilla (Selenicereus megalanthus). Como pretratamiento osmótico a la liofilización (osmoliofilización), las rodajas se sumergieron en una solución de sacarosa con 55 ºBrix a 25ºC; se congelaron a -35°C, la sublimación se llevó a presión de vacío de 8 Pa y el secado se realizó desde -35 hasta 35°C. Los resultados de los tratamientos evidenciaron, al final del proceso, diferencias significativas en la porosidad, volumen y capacidad de rehidratación (que fueron mayores para el tratamiento liofilizado), mientras que la cinética de secado y la actividad de agua no presentaron diferencias significativas. El tratamiento de liofilización fue adecuado para la conservación de rodajas de pitahaya amarilla, ya que permitió reducir la actividad de agua por debajo de 0,4; conservó significativamente el volumen y presentó alta capacidad de rehidratación.

Freeze-drying is an interesting alternative as a food preservation method allowing to extend the shelf life and significantly preserving physical and physicochemical properties related to quality. The objective of this study was to evaluate the effect of freeze-drying and osmo-freeze-drying on the kinetics of freezing and drying, water activity, volume, porosity and rehydration capacity of sliced yellow pitahaya (Selenicereus megalanthus). As osmotic pretreatment to freeze-drying (osmo-freeze-drying), slices were immersed in a sucrose solution at 55°Brix. The slices were frozen at -35°C. The sublimation was carried at vacuum pressure of 8 Pa and drying was carried out from -35 to 35°C. The results of these treatments at the end of the process showed significant differences in porosity, volume and rehydration capacity (being higher for freeze-drying treatment), while the kinetics of drying and water activity were not significant. The freeze drying treatment was suitable for the preservation of sliced yellow pitahaya, because it helped to decrease water activity below 0.4, preserved and showed significant volumes of high rehydration capacity.

Long-term outcomes of quality of life after laparoscopic Nissen fundoplication.

BACKGROUND/AIMS: Several years after the surgery, the results obtained with the operation by Nissen laparoscopy in the treatment of GERD are not sufficiently clarified. Some series reveal good results at short-term; however, the results obtained at long-term are still little known. The aim of our research is to evaluate the results regarding quality of life in patients operated with the laparoscopic Nissen technique. METHODOLOGY: We carried out a study of 143 laparoscopic Nissen's, operated from January 1995 to August 2004. There were 60 men and 83 women with an average age of 49.9 years (18-75); the average follow-up was of 5.42 years (2-11 years). There was no operative mortality; morbidity was of 8.4% and the rate of conversion 2.79%. The analysis of quality of life was made according to our personal questionnaire, consisting of a group of symptoms (23 items) and another related to physical, emotional and psycho-social activities (9 items) duly validated in healthy individuals. We recorded the values corresponding to the sum of the two mentioned groups before and after surgery, referred to in the pre and post-operative according to answers based on an increasing scale of values (from 0 to 3). The higher the score, the higher is the quality of life. In the statistical analysis we resorted to parametric tests (t Student and Anova) and non-parametric (McNemar and Cochran); Values of p < 0.05 were considered significant. RESULTS: The overall analysis in increasing values on a scale of 0 to 3 showed a clear significant improvement of the quality of life after the surgery (+17.50 p < 0.001), although never reaching the values recorded in healthy individuals. Such improvement was more evident in the symptoms group than in the one corresponding to physical, emotional and psycho-social activities (+16.11 vs +2.27, p < 0.001). Among the specific reflux symptoms the ones that benefited most from the surgery were: heartburn (+2.203), regurgitation (+1.95), gastralgia (+1.23) and need to eat slowly (+1.50). Though significant, less satisfactory results were registered in the gas bloating (+0.40), fullness (+0.62) and incapacity to belch (+0.74). In 13.3% it was necessary to resort to medication. In 92.3% the results were considered very good or good and 7.7% bad. There was not any correlation between the quality of life and the different factors included in those operated on: age, sex, operative period, esophagitis and diaphragmatic hernia. CONCLUSION: The Nissen operation by laparoscopy is an excellent option in the treatment of GERD. After it takes place there is a clear improvement in the quality of life of these people, especially in relation to the symptoms typical of GERD; it is, however, less evident in relation to fullness and abdominal bloating.

The efficacy and safety of ezetimibe for treatment of dyslipidemia after heart transplantation.

INTRODUCTION: Statins, although the treatment of choice for dyslipidemia after heart transplantation (HT), are not always well tolerated or effective. In such cases, administration of ezetimibe may be useful. AIM: The aim of this study was to assess the efficacy and safety of ezetimibe, with or without statins, after HT. METHOD: Thirty-six HT patients, 97% of whom were males of overall mean age of 57 +/- 13 years, were all unable to reach target lipid levels with statins alone and/or were intolerant of statins. They were prescribed ezetimibe, with or without a statin. Efficacy and safety were evaluated after 1, 3, 6, and 12 months. RESULTS: Thirty-four patients were evaluated at 1 month and 12 months. Ezetimibe was prescribed to 27 patients (75%) because of statin inefficacy, and to 9 patients (25%) because of statin intolerance, manifested by myalgia in 4 cases (11%), hepatotoxicity in 2 cases (6%), and rhabdomyolysis in 3 cases (8%). Lipid levels (mg/dL; baseline vs 1 year) were as follows: cholesterol, 235 +/- 49 versus 167 +/- 32 (P = .013); LDL cholesterol, 137 +/- 47 versus 89 +/- 29 (P = .001); HDL cholesterol, 54 +/- 13 versus 51 +/- 10 (P = .235); and triglycerides, 243 +/- 187 versus 143 +/- 72 (P = .022). There were no cases of liver toxicity, renal dysfunction, or significant alteration of immunosuppressive pharmacokinetics. Ezetimibe was withdrawn from 2 patients because of hand edema or asymptomatic recurrence of rhabdomyolysis first caused by statins. CONCLUSIONS: With or without a statin, ezetimibe was generally well tolerated, reducing total cholesterol, LDL cholesterol, and triglyceride levels with no long-term alteration of HDL cholesterol levels. CPK surveillance is recommended because of a slight continued risk of adverse effects. Further studies should evaluate the benefit for survival.

Mixed micelles of alkylamines and cetyltrimethylammonium chloride.

The influence of chain length and the nature of the head group on the composition of micelles of a binary mixture of cetyltrimethylammonium chloride with both unsubstituted and N-substituted n-octyl, n-decyl, and n-lauryl amines was established from the variation of the critical micelle concentration (cmc) as a function of the solution composition. A synergistic effect was observed in all instances that were found to be correlated with chain length and the type of N-substituent on the alkylamine head group. Experimental data were compared with theoretical predictions based on the equilibrium between micelles and monomers in solution. The Motomura treatment was used to determine the composition of each compound in the mixed micelles (Xi(m)). Mixing nonideality was expressed in terms of the molecular interaction parameter (beta12) as determined using the theory of Holland and Rubingh. Finally, the molecular thermodynamic model for mixed surfactant systems developed by Puvvada and Blankschtein was used to estimate the micellization free energy (DeltaGM) and to evaluate the synergistic phenomenon.

Adsorption of an amphiphilic penicillin onto human serum albumin: characterisation of the complex.

The complex formed by the interaction of the amphiphilic penicillin drug nafcillin and human serum albumin (HSA) in water at 25 degrees C has been characterised using a range of physicochemical techniques. Measurements of the solution conductivity and the electrophoretic mobility of the complexes have shown an ionic adsorption of the drug on the protein surface leading to a surface saturation at a nafcillin concentration of 0.012 mmol kg(-1) and subsequent formation of drug micelles in solutions of higher nafcillin concentration. Measurements of the size of the complex and the thickness of the adsorbed layer by static and dynamic light scattering have shown a gradual change in hydrodynamic radius of the complex with increasing drug concentration typical of a saturation rather than a denaturation process, the magnitude of the change being insufficient to account for any appreciable extension or unfolding of the HSA molecule. The interaction potential between the HSA/nafcillin complexes, and the stability of the complexes were determined from the dependence of diffusion coefficients on protein concentration by application of the DLVO colloidal stability theory. The results indicate decreasing stability of the colloidal dispersion of the drug/protein complexes with an increase in the concentration of added drug.

Micellar Behavior of n-Alkyl Sulfates in Binary Mixed Systems.

The micellar behavior of the binary mixed systems of sodium n-hexylsulfate with sodium n-decyl-, n-dodecyl-, and n-tetradecylsulfate has been studied. The critical micelle concentration of the mixtures was quantitatively estimated by conductance methods. The micellar composition in the micelles was determined by the Motomura model and the mutual interactions were estimated from Holland and Rubingh's theory. The surfactant mixtures were found to be nonideal. The influence of the alkyl chain length in these parameters was studied. Copyright 2000 Academic Press.

Thermodynamics of Association of Structurally Related Amphiphilic Penicillins.

Critical micelle concentrations (CMCs) of the penicillins cloxacillin and dicloxacillin in water were determined by conductivity measurements over the temperature range 288.15 to 313.15 K. Both penicillins showed minimum CMCs at temperatures close to 298.15 K. Thermodynamic parameters of aggregate formation were derived from the variation of the CMC with temperature using a modified form of the mass action model applicable to systems of low aggregation number. Values for the enthalpy of aggregate formation, DeltaH(0)(m), calculated by this method showed that the aggregation of both cloxacillin and dicloxacillin became increasingly exothermic with increase in temperature. The predicted DeltaH(0)(m) at 298.15 K was in good agreement with the value determined experimentally by calorimetry for each drug. Copyright 2000 Academic Press.

Effect of Electrolyte on the Surface and Thermodynamic Properties of Amphiphilic Penicillins.

Critical micelle concentrations and surface properties of the penicillins cloxacillin, dicloxacillin, and nafcillin in aqueous solution at 303 K and at electrolyte concentrations over the range 0.0-0.4 mol dm(-3) were determined by surface tension measurements. A mass action model, modified for application to associating systems of low aggregation number, was used to calculate the standard Gibbs energy of micellization of these drugs at each electrolyte concentration. Copyright 1999 Academic Press.

Influence of Molecular Structure on the Ideality of Mixing in Micelles Formed in Binary Mixtures of Surface-Active Drugs.

The influence of the structure of the hydrophobic group on the ideality of mixing in binary mixtures of surface active molecules has been investigated using combinations of amphiphilic penicillins. Critical concentrations (cc) of the binary mixtures of these anionic surfactants were determined by conductivity measurements as a function of the composition. The nonideality of mixing was evaluated using a regular solution approximation and expressed in terms of the interaction parameter, beta. Mixing in micelles formed in binary mixtures of the structurally similar penicillins cloxacillin, dicloxacillin, and flucloxacillin was ideal (beta = 0). In contrast, the combination of either cloxacillin or dicloxacillin with the penicillin nafcillin produced mixed micelles in which the mixing deviated from ideality (beta = +0.1 to +0.2). The positive values of beta for these systems indicated negative synergism between components of the mixtures that may be a consequence of the marked structural differences between the hydrophobic groups of these drugs. The composition of the mixed micelles was derived from the cc data by application of a theoretical treatment based on excess thermodynamic quantities. Copyright 1999 Academic Press.

Thermodynamics of Micellization of n-Alkyl Sulfates in an Alkaline Medium at Different Temperatures.

Critical micelle concentrations (cmc) have been calculated from conductivity measurements at 293.15, 298.15, 303.15, 308.15, and 313.15 K for sodium n-decyl sulfate (SDES), sodium n-undecyl sulfate (SUNDS), and sodium n-dodecyl sulfate (SDS) in a medium of pH 10.0 and ionic strength 0.0312. Thermodynamic parameters of micellization, standard Gibbs energies (), standard enthalpies (), and standard entropies (), have been obtained by application of the model of Evans and Ninham in terms of hydrophobic and surface contributions. Copyright 1999 Academic Press.

Thermodynamics of Micellization of Surfactants of Low Aggregation Number: The Aggregation of Propranolol Hydrochloride.

The self-association of propranolol hydrochloride in aqueous solution has been studied as a function of temperature. The critical concentration (C*) and the degree of ionization (alpha) were determined by conductivity measurements at temperatures over the range 298.15 to 313.15 K. The enthalpy change on aggregation in water was measured by microcalorimetry. To calculate changes in the thermodynamic properties of aggregation the mass action model for high and low aggregation numbers was applied, the latter model giving better agreement between experimental and theoretical enthalpy changes. Copyright 1999 Academic Press.