Correlation of Dynamic Surface Tension with Sedimentation of PTFE Particles and Water Penetration in Powders.

The dynamic surface tension of aqueous poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) [(PEO-PPO-PEO)]-type polymeric surfactant (P103, P105, F108, P123, and F127) solutions were correlated with water penetration in packed Teflon powders, the sedimentation of Teflon suspensions in these solutions, foamability, and contact angle measurements on a Teflon surface. The DST trend with bubble lifetime indicated that the overall slowdown in the diffusion process in aqueous solutions is a function of a higher poly(ethylene oxide) (PEO) molecular weight for a given series of block copolymers containing equal PPO molecular weights, favoring slower diffusion kinetics to the air-water interface caused by preferential partitioning in bulk water. The wettability of poly(tetrafluoroethylene) (PTFE) powder illustrates better water penetration for polymers with low molecular weight and lower HLB values. The wettability of F127 solutions decreases with corresponding increases in concentration resulting from higher viscosity, which restrains the diffusion kinetics at the PTFE-water interface. The foamability decreases drastically with higher PEO molecular weight as attributed by slower diffusion kinetics, leading to a decrease in the effective concentration of molecules at the foam interface. The contact angle on glass and the PTFE surface are in good agreement with assumptions made by other analytical techniques showing a lower value of the contact angle with a lower HLB of the Pluronic, which relates to the higher adsorption of molecules at the interface. It is concluded that the adsorption of molecules at the PTFE-water interface decreases in aqueous Pluronic solutions with corresponding increases in the hydrophilic lipophilic balance (HLB), which is consistent with foaming, water penetration in a packed powder of PTFE, the rate of sedimentation, and DST data. A PTFE dispersion containing P123 showed the maximum wettability and lowest sedimentation among the series of block copolymers introduced, which is attributed to faster diffusion kinetics and a higher PPO contribution fostering faster adsorption at the PTFE surface. The dynamic surface tension of aqueous Pluronic solutions seems to correlate well with the adsorption characteristics at the air-water and PTFE-water interfaces.

Novel strategy involving surfactant-polymer combinations for enhanced stability of aqueous teflon dispersions.

Among various polymers, the Teflon surface possesses extreme hydrophobicity (low surface energy), which is of great interest to both industry and academia. In this report, we discuss the stability of aqueous Teflon dispersions (particle size range of 100-3000 nm) formulated by a novel strategy that involves distinct combinations of surfactant and polymer mixtures for dispersion stabilization. As a first step, the hydrophobic Teflon particles were wetted using a range of surfactants (ionic, Triton, Brij, Tween, and Pluronic series) bearing different hydrophobic-lipophilic balance (HLB) and further characterized by contact angle and liquid penetration in packed powder measurements. The interaction between hydrophobic chains of surfactants and the Teflon particle surface is the driving force resulting in wetting of the Teflon particle surface. Further, these wetted particles in aqueous solutions were mixed with various polymers, for example, poly(vinyl alcohol) (PVA), polyvinylpyrrolidone (PVP), hydroxyethyl cellulose (HEC), and hydroxypropyl methyl cellulose (HPMC). The rate of sedimentation for the final dispersions was measured using a pan suspended into the dispersion from a transducer recording the increase in weight with time. A significant stability was noticed for Teflon particles suspended in surfactant + polymer mixtures, which was linearly proportional to the concentration of added polymer. The observed phenomenon can be possibly explained by molecular interactions between the hydrophobic chains of surfactant molecules and polar groups in the polymer architecture. Brij-O10 + HEC mixture was found to be the best surfactant-polymer combination for decreasing the sedimentation of the Teflon particles in the final dispersion. As measured by dynamic light scattering (DLS), the hydrodynamic volume of the Teflon particles increases up to ∼55% in the final formulation. These dispersions could be further explored for various technological applications such as paints, inks, protective coatings, and so forth.

Solution and interfacial self-assembly of Bacillus subtilis bacterial lipoteichoic acid (LTA): nanoclustering, and effects of Ca2+ and temperature.

Lipoteichoic acid (LTA) is a major structural and functional molecule in the Gram-positive bacteria membrane. Knowledge of LTA adsorption at interfaces and its solution self-assembly is crucial to understanding its role in bacterial adhesion and colonisation, infections and inflammations. Here, we report the self-assembly behaviour of LTA extracted from Bacillus subtilis, a Gram-positive bacterium, in an aqueous solution using cryogenic transmission electron microscopy (Cryo-TEM) and small-angle neutron scattering (SANS) and its adsorption behaviour at the solid-liquid interface using atomic force microscopy (AFM) imaging and quartz crystal microbalance with dissipation monitoring (QCM-D). The Cryo-TEM results indicated the formation of spherical LTA micelles that decreased in size on addition of calcium chloride (CaCl2), attributed to charge neutralisation and possible formation of stable Ca2+-bridges between the phosphate groups on neighbouring LTA chains. Analysis of the SANS data from the polydisperse LTA aggregates in solution using the two Lorentzian model revealed the existence of two correlation lengths, which could respectively account for the presence of LTA micelle clusters and the local structure arising from LTA intra-molecular interactions. In the presence of CaCl2, the decrease in the correlation lengths of the clusters indicated possible disruption of H-bonding by Ca2+, leading to poorer water-LTA interactions. At higher temperatures, the correlation length corresponding to the clusters increased, indicating a temperature assisted growth caused by the fluidization of micellar core and dehydration of the polar LTA chains. AFM imaging showed that adsorption of LTA aggregates at the SiO2-water interface was significantly prompted by the addition of CaCl2, also confirmed by QCM-D measurements. These unprecedented nanoscopic structural details on the morphology of LTA aggregates in solution and at the solid-liquid interface add to our fundamental understanding of its self-assembly behaviour hitherto underexplored.

Mixed liposomes containing gram-positive bacteria lipids: Lipoteichoic acid (LTA) induced structural changes.

Lipoteichoic acid (LTA), a surface associated polymer amphiphile tethered directly to the Gram-positive bacterial cytoplasmic membrane, is a key structural and functional membrane component. Its composition in the membrane is regulated by bacteria under different physiological conditions. How such LTA compositional variations modulate the membrane structural stability and integrity is poorly understood. Here, we have investigated structural changes in mixed liposomes mimicking the lipid composition of Gram-positive bacteria membranes, in which the concentration of Bacillus Subtilis LTA was varied between 0-15 mol%. Small-angle neutron scattering (SANS) and dynamic light scattering (DLS) measurements indicated formation of mixed unilamellar vesicles, presumably stabilized by the negatively charged LTA polyphosphates. The vesicle size increased with the LTA molar concentration up to ∼6.5 mol%, accompanied by a broadened size distribution, and further increasing the LTA concentration led to a decrease in the vesicle size. At 80 °C, SANS analyses showed the formation of larger vesicles with thinner shells. Complementary Cryo-TEM imaging confirmed the vesicle formation and the size increase with LTA addition, as well as the presence of interconnected spherical aggregates of smaller size at higher LTA concentrations. The results are discussed in light of the steric and electrostatic interactions of the bulky LTA molecules with increased chain fluidity at the higher temperature, which affect the molecular packing and interactions, and thus depend on the LTA composition, in the membrane.

Thermoresponsive liquid crystalline formulation of Exemestane: Design and structural characterization.

Exemestane (EXE), a drug used for the treatment of breast cancer, has limited aqueous solubility of 0.08 mg/mL and log P∼ 4.22. The only available marketed formulation in form of tablets possess limitations of poor oral absorption (∼ 42 %), low solubility, extensive hepatic metabolism and numerous adverse effects due to its peripheral absorption. In order to address these issues, an alternative route of topical application is attempted through a lamellar liquid crystal based formulation. Pluronic® was used as stabilizer due to its higher surface activity and gelling properties. The solubility enhancement of EXE was achieved using liquid crystal formulation. We have investigated the effect of concentration of oil, Smix (surfactant - cosurfactant mixture) and EXE on lattice parameter, rheology and drug release for various combinations of the formulation. The small angle x-ray scattering (SAXS) measurement demonstrated an evidence of a lamellar structure with lattice parameter ∼15 nm, which increases with corresponding increase in oil and EXE due to increase in hydrophobic interactions leading to an expansion of lamella. The inter lamellar distance decreases at higher surfactant concentration, due to the distribution of the same amount of oil and drug within larger concentration of surfactant molecules. The rheology measurement exhibited gel like properties at low shear rate indicating soft gel formation, which converts to Newtonian type flowing liquid at higher shear rate. At constant Smix with increasing oil content, the viscosity decreases, which is attributed to the dilution of the lamellar structures with oil. The temperature sweep rheology reveals a change in the viscosity near physiological temperature, which may be attributed to the structural transition of lamellae. The formulation remains gel like at room temperature, which aids in proper application to skin and converts it to free flowing liquid above 37 °C. The invitro drug release of optimized formulation for 24 h was ∼ 38 % at 37 °C, which increased to 50 % at 42 °C. Accordingly, this formulation containing thermoresponsive lamellar liquid crystal gels of EXE represents a viable option for hyperthermia induced enhanced drug release. The characteristic and advantageous features offered by this formulation includes improved bioavailability of EXE due to enhanced solubility, permeability and absorption.

Quality by Design approach for an in situ gelling microemulsion of Lorazepam via intranasal route.

The present study illustrates the application of the concept of Quality by Design for development, optimization and evaluation of Lorazepam loaded microemulsion containing ion responsive In situ gelator gellan gum and carbopol 934. A novel approach involving interactions between surfactant and polymer was employed to achieve controlled drug release and reduced mucociliary clearance. Microemulsion formulated using preliminary solubility study and pseudo ternary phase diagrams showed significantly improved solubilization capacity of Lorazepam with 54.31±6.07nm droplets size. The effect of oil to surfactant/cosurfactant ratio and concentration of gelling agent on the drug release and viscosity of microemulsion gel (MEG) was evaluated using a 32 full factorial design. The gel of optimized formulation (MEG1) showed a drug release up to 6h of 97.32±1.35% of total drug loaded. The change in shear-dependent viscosity for different formulations on interaction with Simulated Nasal Fluid depicts the crucial role of surfactant-polymer interactions on the gelation properties along with calcium ions binding on the polymer chains. It is proposed that the surfactant-polymer interactions in the form of a stoichiometric hydrogen bonding between oxyethylene and carboxylic groups of the polymers used, provides exceptional ME stability and adhesion properties. Compared with the marketed formulation, optimized MEG showed improved pharmacodynamic activity. Ex vivo diffusion studies revealed significantly higher release for MEG compared to microemulsion and drug solution. MEG showed higher flux and permeation across goat nasal mucosa. According to the study, it could be concluded that formulation would successfully provide the rapid onset of action, and decrease the mucociliary clearance due to formation of in situ gelling mucoadhesive system.

A multitechnique approach on adsorption, self-assembly and quercetin solubilization by Tetronics® micelles in aqueous solutions modulated by glycine.

Ethylene oxide-propylene oxide (EO-PO) block copolymer micelles are useful potential nanoreservoirs for the delivery of hydrophobic drugs. Considering that glycine is an excipient and can favorably affect the surface/micellar behavior and thus improve solubilization power/dispersion stability/wetting characteristics we have reported here studies on aqueous solution behavior of two commercially available branched block copolymers (Tetronics®) with differing hydrophobicities namely Tetronics® 1307 and 1304, hereafter referred as T1307 and T1304, in the presence of glycine. Steady state fluorescence studies using pyrene as a probe, equilibrium and dynamic surface tension measurements, wetting and dispersion stability studies of Teflon (polytetrafluoroethylene; PTFE) and solubilization studies of a hydrophobic antioxidant/anticancer drug quercetin (QN) have been examined. The cloud point (CP) and critical micelle temperature (CMT) decrease while micelle hydrodynamic size (Dh) increases with the addition of glycine as well as on loading of the drug in the micelles. Water penetration through packed PTFE powder and dynamic surface tension confirm the enhanced micellization process for aqueous Tetronic® solutions in presence of glycine and accordingly restricted diffusion for the surfactant molecules towards air-water and PTFE-water interface. The contact angles for Tetronic® solutions in presence of glycine indicate moderate decrease. The pressure-area curves of the copolymers in water and glycine solutions were also constructed. Surface and micellar properties of copolymers are markedly altered in the presence of glycine and can be tuned for use of these nanocarriers in delivery systems.