Influence of fines on the surface energy heterogeneity of lactose for pulmonary drug delivery.

The effects of the blending of lactose fines to the overall adhesion property of coarse alpha-lactose monohydrate carrier particles were investigated. Five samples, three of them commercial samples from DOMO (Lactohale) LH100, LH210, and LH250) whilst the other two are blends of LH210 and LH250, were studied. Characterisation included particle sizing, SEM, PXRD and IGC. Dispersive surface energy gamma(SV)(d) was determined using a finite concentration IGC method to obtain a distribution profile. The gamma(SV)(d) distribution of lactose crystals was found to vary from 40 to 48mJ/m(2). The unmilled coarse crystalline lactose sample (LH100) gamma(SV)(d) was lowest and showed less heterogeneity than the milled sample (LH250). Fines (LH210) were found to have the highest gamma(SV)(d) value. The samples with loaded LH210 were found to have a higher energy than LH100. The amount of LH210 in Blend 1 was not able to decrease surface energy heterogeneity, whereas sample Blend 2 showed adequate loading of fines to obtain a relatively homogeneous surface. Addition of fines resulted in an increase in gamma(SV)(d), suggesting that coarse lactose surfaces were replaced by surfaces of the fines. Increasing the loading of fines may result in a more homogeneous surface energy of lactose particles.

Road to disorder in smectic elastomers.

We present a high-resolution x-ray study of the effects of disorder induced by random cross-linking side-chain smectic elastomers. The influence of variation of the concentration and stiffness of the cross-link units on the disruption of the one-dimensional translational order is reported in detail. Precise analysis of the line shape of the quasi-Bragg peaks associated with the smectic layering indicates a transition from algebraic decaying ordering to disorder. The smectic line shapes can be described by the Caillé correlation function convoluted with a finite-size factor represented by a stretched Gaussian (compressed exponential). The transition to disorder is signaled by a change in the exponent of the stretched Gaussian from 1 (simple Gaussian describing finite-size domains) via 0.5 (Lorentzian describing exponentially decaying short-range correlations) to <0.5 (stretched exponential correlations). For a flexible cross linker the changeover occurs for concentration between 0.15 and 0.20, for a stiff cross linker below about 0.10. Broadening of the higher harmonics of the x-ray peak indicates strong nonuniform strain within finite-size domains and local deformations induced by randomly distributed dislocations.

Dynamic heterogeneity in hydrogen-bonded polymers.

We report on neutron spin echo experiments on hydrogen-bonded polymers and compare the experimentally found dynamical structure factor with theoretical predictions. Surprisingly, we find that in the melt phase the expected scaling of the Rouse dynamics is not satisfied. We propose an explanation based upon the large spatial volume occupied by the connecting groups. When the effects of these bulky groups on the local friction are taken into account, the usual scaling behavior is restored.

MRI of perfluorocarbon emulsion kinetics in rodent mammary tumours.

Perfluorocarbon (PFC) emulsions can be imaged directly by fluorine-19 MRI. We developed an optimized protocol for preparing PFC droplets of uniform size, evaluated use of the resulting droplets as blood pool contrast agents, studied their uptake by tumours and determined the spatial resolution with which they can be imaged at 4.7 T. Perfluorocarbon droplets of three different average sizes (324, 293 and 225 nm) were prepared using a microemulsifier. Images of PFC droplets with good signal-to-noise ratio were acquired with 625 microm in-plane resolution, 3 mm slice thickness and acquisition time of approximately 4.5 min per image. Kinetics of washout were determined using a simple mathematical model. The maximum uptake of the PFC droplets was three times greater at the tumour rim than in muscle, but the washout rate was two to three times slower in the tumour. The results are consistent with leakage of the droplets into the tumour extravascular space due to the hyper-permeability of tumour capillaries. PFC droplets may allow practical and quantitative measurements of blood volume and capillary permeability in tumours with reasonable spatial resolution.

Interaction of antimicrobial peptide protegrin with biomembranes.

The antimicrobial peptide protegrin-1 (PG-1) interacts with membranes in a manner that strongly depends on membrane lipid composition. In this research we use an approach representing the outer layers of bacterial and red blood cell membranes with lipid monolayers and using a combination of insertion assay, epifluorescence microscopy, and surface x-ray scattering to gain a better understanding of antimicrobial peptide's mechanism of action. We find that PG-1 inserts readily into anionic dipalmitoyl-phosphatidylglycerol, palmitoyl-oleoyl-phosphatidylglycerol, and lipid A films, but significantly less so into zwitterionic dipalmitoyl-phosphatidylcholine, palmitoyl-oleoyl-phosphatidylcholine, and dipalmitoyl-phosphatidylethanolamine monolayers under similar experimental conditions. Epifluorescence microscopy shows that the insertion of PG-1 into the lipid layer results in the disordering of lipid packing; this disordering effect is corroborated by grazing incidence x-ray diffraction data. X-ray reflectivity measurements further point to the location of the peptide in the lipid matrix. In a pathologically relevant example we show that PG-1 completely destabilizes monolayer composed of lipid A, the major component in the outer membrane of Gram-negative bacteria, which is likely to be the mechanism by which PG-1 disrupts the outer membrane, thus allowing it to reach the target inner membrane.