DNA-lipid systems: A physical chemistry study

It is well known that the interaction of polyelectrolytes with oppositely charged surfactants leads to an associative phase separation; however, the phase behavior of DNA and oppositely charged surfactants is more strongly associative than observed in other systems. A precipitate is formed with very low amounts of surfactant and DNA. DNA compaction is a general phenomenon in the presence of multivalent ions and positively charged surfaces; because of the high charge density there are strong attractive ion correlation effects. Techniques like phase diagram determinations, fluorescence microscopy, and ellipsometry were used to study these systems. The interaction between DNA and catanionic mixtures (i.e., mixtures of cationic and anionic surfactants) was also investigated. We observed that DNA compacts and adsorbs onto the surface of positively charged vesicles, and that the addition of an anionic surfactant can release DNA back into solution from a compact globular complex between DNA and the cationic surfactant. Finally, DNA interactions with polycations, chitosans with different chain lengths, were studied by fluorescence microscopy, in vivo transfection assays and cryogenic transmission electron microscopy. The general conclusion is that a chitosan effective in promoting compaction is also efficient in transfection.

Modulating self-assembly of a nanotape-forming peptide amphiphile with an oppositely charged surfactant

A peptide amphiphile (PA) C16-KTTKS, containing a pentapeptide headgroup based on a sequence from procollagen I attached to a hexadecyl lipid chain, self-assembles into extended nanotapes in aqueous solution. The tapes are based on bilayer structures, with a 5.2 nm spacing. Here, we investigate the effect of addition of the oppositely charged anionic surfactant sodium dodecyl sulfate (SDS) via AFM, electron microscopic methods, small-angle X-ray scattering and X-ray diffraction among other methods. We show that addition of SDS leads to a transition from tapes to fibrils, via intermediate states that include twisted ribbons. Addition of SDS is also shown to enhance the development of remarkable lateral ‘‘stripes’’ on the nanostructures, which have a 4 nm periodicity. This is ascribed to counterion condensation. The transition in the nanostructure leads to changes in macroscopic properties, in particular a transition from sol to gel is noted on increasing SDS (with a further reentrant transition to sol on further increase of SDS concentration). Formation of a gel may be useful in applications of this PA in skincare applications and we show that this can be controlled via development of a network of fine stranded fibrils.

Complex formation in solutions of oppositely charged polyelectrolytes at different polyion compositions and salt content

The formation of complexes in solutions containing positively charged polyions (polycations) and a variable amount of negatively charged polyions (polyanions) has been investigated by Monte Carlo simulations. The polyions were described as flexible chains of charged hard spheres interacting through a screened Coulomb potential. The systems were analyzed in terms of cluster compositions, structure factors, and radial distribution functions. At 50% charge equivalence or less, complexes involving two polycations and one polyanion were frequent, while closer to charge equivalence, larger clusters were formed. Small and neutral complexes dominated the solution at charge equivalence in a monodisperse system, while larger clusters again dominated the solution when the polyions were made polydisperse. The cluster composition and solution structure were also examined as functions of added salt by varying the electrostatic screening length. The observed formation of clusters could be rationalized by a few simple rules.

Adsorption of polyelectrolytes onto oppositely charged cylindrical macroions

In this work we investigate the adsorption of polyelectrolyte chains onto uniformly charged cylindrical macroions by means of the Metropolis Monte Carlo simulations and weighted histogram analysis method. Adopting a simplified model for macromolecules and treating the electrolytic solution in the Debye-Hückel level, conformational properties of the adsorbed chain, such as the radius of gyration and the thickness of the adsorbed layer, are provided as a function of ionic strength and macroion charge density. By analysis of the free energy profile as a function of the radius of gyration it was possible to identify first-order-like transitions between adsorbed and desorbed states and obtain a macroion charge density dependence of the critical ionic strength in good agreement with experiments. © 2013 AIP Publishing LLC.

Oppositely charged polyelectrolytes: complex formation and effects of chain asymmetry

The formation of complexes in solutions of oppositely charged polyions has been studied by Monte Carlo simulations. The amount as well as the length, and thus, the absolute charge of one of the polyions have been varied. There is an increasing tendency to form large clusters as the excess of one kind of polyion decreases. When all polyions have the same length, this tendency reaches a maximum near, but off, equivalent amounts of the two types of polyions. When one kind of polyion is made shorter, the propensity to form large clusters decreases and the fluctuations in cluster charge increases. Simple free-energy expressions have been formulated on the basis of a set of simple rules that help rationalize the observations. By calculating cluster distributions in both grand canonical and canonical ensembles, it has been possible to show the extent of finite-size effects in the simulations.

A Monte Carlo study of solutions of oppositely charged polyelectrolytes

The formation of complexes appearing in solutions containing oppositely charged polyelectrolytes has been investigated by Monte Carlo simulations using two different models. The polyions are described as flexible chains of 20 connected charged hard spheres immersed in a homogenous dielectric background representing water. The small ions are either explicitly included or their effect described by using a screened Coulomb potential. The simulated solutions contained 10 positively charged polyions with 0, 2, or 5 negatively charged polyions and the respective counterions. Two different linear charge densities were considered, and structure factors, radial distribution functions, and polyion extensions were determined. A redistribution of positively charged polyions involving strong complexes formed between the oppositely charged polyions appeared as the number of negatively charged polyions was increased. The nature of the complexes was found to depend on the linear charge density of the chains. The simplified model involving the screened Coulomb potential gave qualitatively similar results as the model with explicit small ions. Finally, owing to the complex formation, the sampling in configurational space is nontrivial, and the efficiency of different trial moves was examined.

Coassembly in binary mixtures of peptide amphiphiles containing oppositely charged residues

The self-assembly in water of designed peptide amphiphile (PA) C16-ETTES containing two anionic residues and its mixtures with C16-KTTKS containing two cationic residues has been investigated. Multiple spectroscopy, microscopy, and scattering techniques are used to examine ordering extending from the β-sheet structures up to the fibrillar aggregate structure. The peptide amphiphiles both comprise a hexadecyl alkyl chain and a charged pentapeptide headgroup containing two charged residues. For C16-ETTES, the critical aggregation concentration was determined by fluorescence experiments. FTIR and CD spectroscopy were used to examine β-sheet formation. TEM revealed highly extended tape nanostructures with some striped regions corresponding to bilayer structures viewed edge-on. Small-angle X-ray scattering showed a main 5.3 nm bilayer spacing along with a 3 nm spacing. These spacings are assigned respectively to predominant hydrated bilayers and a fraction of dehydrated bilayers. Signs of cooperative self-assembly are observed in the mixtures, including reduced bundling of peptide amphiphile aggregates (extended tape structures) and enhanced β-sheet formation.

Development and In Vitro Evaluation of Surfactant Systems for Controlled Release of Zidovudine

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Surfactant systems for nasal zidovudine delivery: structural, rheological and mucoadhesive properties

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Search for Higgs boson production in oppositely charged dilepton and missing energy events in pp̄ collisions at √s=1.96TeV

We present a search for the standard model Higgs boson using events with two oppositely charged leptons and large missing transverse energy as expected in H→WW decays. The events are selected from data corresponding to 8.6fb -1 of integrated luminosity in pp̄ collisions at √s=1.96TeV collected with the D0 detector at the Fermilab Tevatron Collider. No significant excess above the standard model background expectation in the Higgs boson mass range this search is sensitive to is observed, and upper limits on the Higgs boson production cross section are derived. © 2012 American Physical Society.

Hydrodynamics and solid dosage form disintegration/dissolution : immediate release tablets and novel in situ polyelectrolyte gastroretentive drug delivery systems

Solid oral dosage form disintegration in the human stomach is a highly complex process dependent on physicochemical properties of the stomach contents as well as on physical variables such as hydrodynamics and mechanical stress. Understanding the role of hydrodynamics and forces in disintegration of oral solid dosage forms can help to improve in vitro disintegration testing and the predictive power of the in vitro test. The aim of this work was to obtain a deep understanding of the influence of changing hydrodynamic conditions on solid oral dosage form performance. Therefore, the hydrodynamic conditions and forces present in the compendial PhEur/USP disintegration test device were characterized using a computational fluid dynamics (CFD) approach. Furthermore, a modified device was developed and the hydrodynamic conditions present were simulated using CFD. This modified device was applied in two case studies comprising immediate release (IR) tablets and gastroretentive drug delivery systems (GRDDS). Due to the description of movement provided in the PhEur, the movement velocity of the basket-rack assembly follows a sinusoidal profile. Therefore, hydrodynamic conditions are changing continually throughout the movement cycle. CFD simulations revealed that the dosage form is exposed to a wide range of fluid velocities and shear forces during the test. The hydrodynamic conditions in the compendial device are highly variable and cannot be controlled. A new, modified disintegration test device based on computerized numerical control (CNC) technique was developed. The modified device can be moved in all three dimensions and radial movement is also possible. Simple and complex moving profiles can be developed and the influence of the hydrodynamic conditions on oral solid dosage form performance can be evaluated. Furthermore, a modified basket was designed that allows two-sided fluid flow. CFD simulations of the hydrodynamics and forces in the modified device revealed significant differences in the fluid flow field and forces when compared to the compendial device. Due to the CNC technique moving velocity and direction are arbitrary and hydrodynamics become controllable. The modified disintegration test device was utilized to examine the influence of moving velocity on disintegration times of IR tablets. Insights into the influence of moving speed, medium viscosity and basket design on disintegration times were obtained. An exponential relationship between moving velocity of the modified basket and disintegration times was established in simulated gastric fluid. The same relationship was found between the disintegration times and the CFD predicted average shear stress on the tablet surface. Furthermore, a GRDDS was developed based on the approach of an in situ polyelectrolyte complex (PEC). Different complexes composed of different grades of chitosan and carrageenan and different ratios of those were investigated for their swelling behavior, mechanical stability, and in vitro drug release. With an optimized formulation the influence of changing hydrodynamic conditions on the swelling behavior and the drug release profile was demonstrated using the modified disintegration test device. Both, swelling behavior and drug release, were largely dependent on the hydrodynamic conditions. Concluding, it has been shown within this thesis that the application of the modified disintegration test device allows for detailed insights into the influence of hydrodynamic conditions on solid oral dosage form disintegration and dissolution. By the application of appropriate test conditions, the predictive power of in vitro disintegration testing can be improved using the modified disintegration test device. Furthermore, CFD has proven a powerful tool to examine the hydrodynamics and forces in the compendial as well as in the modified disintegration test device. rn

Counter-ion effect on surfactant-DNA gel particles as controlled DNA delivery systems

The ability to entrap drugs within vehicles and subsequently release them has led to new treatments for a number of diseases. Based on an associative phase separation and interfacial diffusion approach, we developed a way to prepare DNA gel particles without adding any kind of cross-linker or organic solvent. Among the various agents studied, cationic surfactants offered particularly efficient control for encapsulation and DNA release from these DNA gel particles. The driving force for this strong association is the electrostatic interaction between the two components, as induced by the entropic increase due to the release of the respective counter-ions. However, little is known about the influence of the respective counter-ions on this surfactant-DNA interaction. Here we examined the effect of different counter-ions on the formation and properties of the DNA gel particles by mixing DNA (either single-(ssDNA) or double-stranded (dsDNA)) with the single chain surfactant dodecyltrimethylammonium (DTA). In particular, we used as counter-ions of this surfactant the hydrogen sulfate and trifluoromethane sulfonate anions and the two halides, chloride and bromide. Effects on the morphology of the particles obtained, the encapsulation of DNA and its release, as well as the haemocompatibility of these particles are presented, using counter-ion structure and DNA conformation as controlling parameters. Analysis of the data indicates that the degree of counter-ion dissociation from the surfactant micelles and the polar/hydrophobic character of the counter-ion are important parameters in the final properties of the particles. The stronger interaction with amphiphiles for ssDNA than for dsDNA suggests the important role of hydrophobic interactions in DNA.

Critical adsorption of polyelectrolytes onto charged Janus nanospheres

Based on extensive Monte Carlo simulations and analytical considerations we study the electrostatically driven adsorption of flexible polyelectrolyte chains onto charged Janus nanospheres. These net-neutral colloids are composed of two equally but oppositely charged hemispheres. The critical binding conditions for polyelectrolyte chains are analysed as function of the radius of the Janus particle and its surface charge density, as well as the salt concentration in the ambient solution. Specifically for the adsorption of finite-length polyelectrolyte chains onto Janus nanoparticles, we demonstrate that the critical adsorption conditions drastically differ when the size of the Janus particle or the screening length of the electrolyte are varied. We compare the scaling laws obtained for the adsorption-desorption threshold to the known results for uniformly charged spherical particles, observing significant disparities. We also contrast the changes to the polyelectrolyte chain conformations close to the surface of the Janus nanoparticles as compared to those for simple spherical particles. Finally, we discuss experimentally relevant physicochemical systems for which our simulations results may become important. In particular, we observe similar trends with polyelectrolyte complexation with oppositely but heterogeneously charged proteins.

Role of surfactants in filtration and fouling of colloidal silica

The EM3E Master is an Education Programme supported by the European Commission, the European Membrane Society (EMS), the European Membrane House (EMH), and a large international network of industrial companies, research centres and universities

Formation of polyelectrolyte multilayers and polyelectrolyte complexes in dual polymer treatment of papermaking pulp

The goal of this study was to find a new approach to modify chemically the properties of paper by improving fiber quality. This Master’s thesis includes the multiple polymer treatment in general and themeasurement methods with which the formation of multilayers and complexes can be noticed. The treatment by an oppositely charged dual polymer system is a good approach to increase paper strength. In this work, starch, a cationic polymer, and carboxymethyl cellulose (CMC), an anionic polymer, were used step-by-step to improve paper strength. The adsorption of cationic starch and CMC on cellulose fibers were analyzed via polyelectrolyte titration. The results showed that paper strength was enhanced slightly with a layer-by-layer assembly of the polymers. However, if the washing stage, which was required for layer-by-layer assembly, was eliminated, the starch/CMC complex was deposited on fibers more efficiently, and the paper strength was improved more significantly.