Aggregate Free Solution Research Articles

Developing an Efficacious Diclofenac Diethylamine Transdermal Formulation

The aim of current study was to develop an efficacious topical formulation of diclofenac diethylamine (DDA), for eventual use as a locally applied analgesic lotion. A series of lotions were prepared that incorporated 2% w/v DDA but a variable (1, 2, 3 or 4% v/v) concentration of oleic acid (permeation enhancer)-turpentine oil binary mixture (1:1 v/v). After measurements of each lotion's visual appearance, viscosity, spreadability, pH and long term stability, a diffusion cell method was employed to quantify DDA permeation from each lotion across both silicone membranes and rabbit skin. Subsequently, three distinct in vivo animal models were utilised to evaluate each lotion's induced anti-inflammatory, antinociception and irritancy effects. Lastly, a panel of human volunteers assessed the subjective sensory feel of each lotion as well as its potential for cutaneous irritancy following a brief application. Upon preparation, all four DDA-containing lotions (L1, L2, L3 and L4) appeared as clear, colourless, homogenous and aggregate-free solutions. All the lotions exhibited a pH of ~6.2 with non-significant (p ＞ 0.05) differences between each formulation (data not shown). Increasing the formulation's oleic acid concentration yielded a general trend of mild enhancement of DDA transport across silicone membrane and dramatic improvements of DDA flux through rabbit skin. Application of each of the DDA-containing formulations significantly reduced tissue inflammation in the rabbit model. It was determined that the DDA lotion containing 4% v/v oleic acid exhibited the best performance overall and that this specific formulation should be the basis for further clinical investigation.

Redox-active polyamine-salt aggregates as multistimuli-responsive soft nanoparticles.

Polyamine-salt aggregates have become promising soft materials in nanotechnology due to their easy preparation process and pH-responsiveness. Here, we report the use of hexacyanoferrate(ii) and hexacyanoferrate(iii) as electroactive crosslinking agents for the formation of nanometer-sized redox-active polyamine-redox-salt aggregates (rPSA) in bulk suspension. This nanoplatform can be selectively assembled or disassembled under different stimuli such as redox environment, pH and ionic strength. By changing the charge of the building blocks, external triggers allow switching the system between two phase states: aggregate-free solution or colloidal rPSA dispersion. The stimuli-activated modulation of the assembly/disassembly processes opens a path to exploit rPSA in technologies based on smart nanomaterials.

Ammonium hydroxide treatment of Aβ produces an aggregate free solution suitable for biophysical and cell culture characterization

Alzheimer’s disease is the leading cause of dementia in the elderly. Pathologically it is characterized by the presence of amyloid plaques and neuronal loss within the brain tissue of affected individuals. It is now widely hypothesised that fibrillar structures represent an inert structure. Biophysical and toxicity assays attempting to characterize the formation of both the fibrillar and the intermediate oligomeric structures of Aβ typically involves preparing samples which are largely monomeric; the most common method by which this is achieved is to use the fluorinated organic solvent 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP). Recent evidence has suggested that this method is not 100% effective in producing an aggregate free solution. We show, using dynamic light scattering, size exclusion chromatography and small angle X-ray scattering that this is indeed the case, with HFIP pretreated Aβ peptide solutions displaying an increased proportion of oligomeric and aggregated material and an increased propensity to aggregate. Furthermore we show that an alternative technique, involving treatment with strong alkali results in a much more homogenous solution that is largely monomeric. These techniques for solubilising and controlling the oligomeric state of Aβ are valuable starting points for future biophysical and toxicity assays.

Characterization of Polymer Solutions Containing a Small Amount of Aggregates by Static and Dynamic Light Scattering

Aggregate-containing solutions of poly(n-hexyl isocyanate) (PHIC) and atactic polystyrene of finite concentrations were studied by static and dynamic light scattering. Their static structure factors Ŝ(k) and the intensity autocorrelation functions g(2)(t) exhibited the enhanced low-angle scattering and bimodal relaxation, respectively. From Ŝ(k) and g(2)(t) obtained, the fast- and slow-mode components of the static structure factor (Ŝfast(k) and Ŝslow(k)) and of the first cumulant (Γfast and Γslow) were estimated as functions of the magnitude of the scattering vector k. As verified by a theory based on the dynamic mean-field theory, if the solution contains only a small amount of aggregates with diffusion coefficients much smaller than that of the nonaggregating component, Ŝfast(k) and Γfast give us the osmotic compressibility ∂c/∂Π and mutual diffusion coefficient Dm of aggregate-free solutions, respectively, and Ŝslow(k) and Γslow provide us the radius of gyration 〈S2〉z,A1/2 and hydrodynamic radius RH,A...

Size exclusion chromatographic measurement of PVC molecular weight distributions

AbstractAggregates that may exist in poly(vinyl chloride) (PVC) solutions at ambient temperatures compromise the accuracy of SEC measurements of molecular weight distributions. Aggregate‐free solutions can be produced in 1,2,4‐trichlorobenzene (TCB) by controlling the dissolution time and temperature. SEC measurements were made in trichlorobenzene at 110°C after dissolution for 12 h at 120°C. An on‐line continuous viscometer can be used to determine when aggregate‐free solutions have been produced. The Mark‐Houwink parameters (K = 0.161 mL/g, α = 0.762) can be used for universal calibration procedures in TCB at 110°C. Complete dissolution of the PVC affects the high molecular weight end of the molecular weight distribution. Measured M̄n values are not affected, but Mz's are much higher than those estimated, for example, from room‐temperature SEC analyses in tetrahydrofuran. Molecular weight distributions are also seen to be broader, especially for higher molecular weight PVCs. © 1993 John Wiley & Sons, Inc.

High temperature GPC of polypropylene

AbstractThe highest temperature at which molecular weight distributions can be characterized by current techniques is 145°C. Supermolecular aggregates may exist at this temperature in polypropylene solutions in trichlorobenzene and other solvents. Dissolution procedures at higher temperatures are ineffective in this case because of the limited thermal stability of polypropylene. Aggregate‐free solutions can be prepared, however, by controlling storage times at 145°C in mixtures with added stabilizers. Low angle laser light scattering measurements can be used to determine when true solutions have been produced. This occurs when measured second virial coefficients agree with values predicted for the Mw measured in the light scattering experiment. GPC–LALLS measurements of Mw and Mz provide similar information about the effects of storage time on dissolution of aggregates and polymer degradation.