Hybrid Methacrylated Gelatin and Hyaluronic Acid Hydrogel Scaffolds. Preparation and Systematic Characterization for Prospective Tissue Engineering Applications.

Hyaluronic acid (HA) and gelatin (Gel) are major components of the extracellular matrix of different tissues, and thus are largely appealing for the construction of hybrid hydrogels to combine the favorable characteristics of each biopolymer, such as the gel adhesiveness of Gel and the better mechanical strength of HA, respectively. However, despite previous studies conducted so far, the relationship between composition and scaffold structure and physico-chemical properties has not been completely and systematically established. In this work, pure and hybrid hydrogels of methacroyl-modified HA (HAMA) and Gel (GelMA) were prepared by UV photopolymerization and an extensive characterization was done to elucidate such correlations. Methacrylation degrees of ca. 40% and 11% for GelMA and HAMA, respectively, were obtained, which allows to improve the hydrogels' mechanical properties. Hybrid GelMA/HAMA hydrogels were stiffer, with elastic modulus up to ca. 30 kPa, and porous (up to 91%) compared with pure GelMA ones at similar GelMA concentrations thanks to the interaction between HAMA and GelMA chains in the polymeric matrix. The progressive presence of HAMA gave rise to scaffolds with more disorganized, stiffer, and less porous structures owing to the net increase of mass in the hydrogel compositions. HAMA also made hybrid hydrogels more swellable and resistant to collagenase biodegradation. Hence, the suitable choice of polymeric composition allows to regulate the hydrogels´ physical properties to look for the most optimal characteristics required for the intended tissue engineering application.

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.

Poly-(cyclo)dextrins as ethoxzolamide carriers in ophthalmic solutions and in contact lenses.

Efficient ophthalmic therapy requires the development of strategies that can provide sufficiently high drug levels in the ocular structures for a prolonged time. This work focuses on the suitability of poly-(cyclo)dextrins as carriers able to solubilize the carbonic anhydrase inhibitor (CAI) ethoxzolamide (ETOX), which is so far used for oral treatment of glaucoma. Topical ocular treatment should notably enhance the efficiency/safety profile of the drug. Natural α-, ß- and γ-cyclodextrins and a maltodextrin were separately polymerized using citric acid as cross-linker agent under mild conditions. The resultant hydrophilic polymers exhibited larger capability to solubilize ETOX than the pristine (cyclo)dextrins. Moreover, they provided sustained drug diffusion in artificial lachrymal fluid. Interestingly the poly-(cyclo)dextrins solutions facilitate the loading of remarkably high doses of ETOX in poly(2-hydroxyethyl methacrylate)-based contact lenses. Exploiting ionic interactions between functional groups in the contact lenses and remnant free carboxylic acids in the citric acid linkers of poly-(cyclo)dextrins led to the retention of the drug-loaded poly-(cyclo)dextrins and, in turn, to sustained release for several weeks.

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.

Hydration and nutrition at the end of life: a systematic review of emotional impact, perceptions, and decision-making among patients, family, and health care staff.

BACKGROUND: Decrease in oral intake, weight loss, and muscular weakness in the last phases of a terminal illness, particularly in the context of the cachexia-anorexia syndrome, can be an important source of anxiety for the triad of patient, family, and health staff. METHODS: The present literature review examines the emotional impact of reduced oral intake as well as perceptions and attitudes toward assisted nutrition and hydration for terminally ill patients(1) at the end of life, among patients, family, and health care staff. We have identified the ways in which emotional and cultural factors influence decision-making about assisted nutrition and hydration. RESULTS: Lack of information and misperceptions of medically assisted nutrition and hydration can play a predominant role in the decision to begin or suspend nutritional or hydration support. CONCLUSIONS: Our literature review reveals that these social, emotional, and clinical misperception elements should be considered in the decision-making processes to help the triad develop functional forms of care at this final stage of life. Copyright © 2011 John Wiley & Sons, Ltd.

Phase behavior of the Pluronic P103/water system in the dilute and semi-dilute regimes.

The detailed temperature-composition phase diagram of the P103/water system in the dilute and semidilute regions is reported here using density and ultrasound velocity measurements, differential scanning calorimetry (DSC), rheometry and dynamic (DLS) and static light scattering (SLS). These techniques allow a precise determination of the critical micellar temperature (CMT), the sphere-to-rod micellar transition temperature (GMT) and the cloud point temperature (CPT) as a function of concentration. DLS and SLS measurements were employed to gain information on unimers and aggregate sizes and on the transition from spherical-to-rod micelles.

Obstrução gástrica por pólipos múltiplos em Akita. Relato de caso

O artigo não apresenta resumo.

Estenose esofágica por Tricobezoar gástrico no cão. Relato de caso

O artigo não apresenta resumo.

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.

Ethical decision-making on communication in palliative cancer care: a personalist approach.

Perhaps one of the main ethical dilemmas physicians face in cancer medicine is the question of truthfulness with terminally ill cancer patients. Reluctance to share the truth with the patient about his or her diagnosis and/or prognosis is frequently associated with cultural pressures. Based on two cases, the authors illustrate how ethical analysis can help in solving dilemmas related to truth disclosure to terminally ill cancer patients and their families. A personalist approach reveals that the often-adduced conflict between nonmaleficence/beneficence and autonomy with regard to truth telling originates from a narrow understanding of the concept of autonomy. This confrontation is, therefore, more apparent than real. A brief review of the main ethical systems and the results of their application to clinical decision-making follow the discussion of the cases.

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.

Hazard Analyses of Foods Prepared by Migrants Living in a New Settlement at the Outskirts of Lima, Peru.

Hazard analyses of food preparation practices were conducted in three households in a new settlement in the rocky, dusty hillsides at the outskirts of Lima, Peru. These analyses consisted of watching all steps of preparation, recording temperatures throughout these steps, and collecting samples of the food and testing them for common foodborne pathogens and indicator organisms. The residents had migrated from different regions of the country; consequently, they prepared different foods. These included soya cereal, milk formula, rice and carrots for feeding a baby who had diarrhea, soups, mashed potatoes with spinach, carrot and beet salad, cow's foot soup, beans, rice and a mixture of beans and rice. The temperatures attained were high enough to kill vegetative forms of foodborne pathogens, but not their spores. During the interval between cooking in the morning and serving at either lunch or supper time, foods were held either on unheated ranges or in unheated ovens. This interval was long enough to permit some bacterial multiplication, but apparently not to massive quantities. Just before the evening meal, foods were reheated to temperatures that usually exceeded 70°C. Rice, however, was either served cold or if reheated, the center temperature rose a few degrees only. Critical control points for preparation of family meals are cooking, holding between cooking and serving, and reheating. Critical control points for milk formula for babies are using recently-boiled water for the formula, cleaning and boiling bottles and nipples, and, of particular importance, time of holding at room temperature.