Biomedical subjects
Publications and source records attributed to Dave E Dunstan.
Mixtures of silver(I) and citrate that are used to produce silver nanoparticles evoke intense chemiluminescence with tris(2,2'-bipyridyl)ruthenium(II) and cerium(IV), which can be exploited for the determination of citrate ions and other analytes over a wide concentration range.
The formation of self assembled nano-structures from the biopolymer laminarin dried onto mica is reported. The observed structures are composed of stacked terraced layers decreasing in size away from the mica surface. The layers display a high degree of dimensional regularity as observed using atomic force microscope imaging (AFM). The width of the layers is linearly dependent upon the number of layers in the structure and decreases with layer number away from the mica substrate. The thickness of the layers is uniform throughout the structure. A pore is contained in the central region of each structure with more than one layer. We postulate that these structures have potential use as templates in microelectronic devices and sensors where the central pore has the potential to immobilise functional materials.
Shear flow is indirectly implicated in amyloid formation in vitro. Despite the association between amyloid fibrils and disease, and the prevalence of flow in physiological systems, the effect of this parameter is uncharacterized. We designed a novel Couette cell to quantitatively investigate shear exposure during fibrillogenesis. Amyloid formation by beta-lactoglobulin was monitored in situ with real-time fluorescence measurements across a range of shear rates. We demonstrate shear-induced aggregation of spheroidal seed-like species. These seeds enhance fibril formation in native beta-lactoglobulin, thereby demonstrating that shear flow generates an amyloidogenic precursor. Furthermore, preformed fibrils are degraded by exposure to high shear rates. Our results have implications for the mechanism of amyloid formation in physiological flow conditions.
A novel rheofluorescence technique has been developed that permits the study of fluorescent polymers in a near-uniform shear field. The system has been used to examine the effects of shear flow on dilute solutions of two commercially available samples of poly[2-methoxy-5-(2-ethylhexyloxy)-1,4-phenylenevinylene] (MEH-PPV) in toluene and xylene. A detailed description of the instrument is provided, along with data that confirm a small probe molecule, Rhodamine 6G, is not affected by simple shear flow. MEH-PPV solutions were examined over two decades of concentration for rheochromism indicative of changes in segment length, and shear-induced orientation revealed by measurements of the steady state emission anisotropy. It is demonstrated that these dilute samples were not influenced by shear rates in the range 100-1000 s(-1). In contrast, MEH-PPV dispersed in a concentrated polystyrene solution showed evidence of shear-induced orientation and rheochromism. This new technique shows promise for investigating the impact of shear flow on the conformation of conjugated polymers employed in organic optoelectronic devices.
The formation of lyotropic phases resulting from the digestion of formulation lipids has a pronounced impact on the intestinal solubilization and resultant bioavailability of poorly water-soluble drugs. In this study, phase diagrams were produced to determine the phase behavior of the digestion products of common formulation lipids (C8:0, C12:0, and C18:1) under model physiological conditions. Pseudoternary phase diagrams were constructed using varying proportions of SEIF (Simulated Endogenous Intestinal Fluid) and fatty acid (FA) and monoglyceride (MG) (as representative exogenous lipid digestion products). A change from liquid crystal to colloidal liquid (containing mixed micelles and vesicles) was observed with decreasing FA/MG concentrations. The solubilization enhancement ratio (SER) afforded by these phases for a series of poorly water-soluble compounds (hydrocortisone and hydrocortisone esters, clogP = 1.4 to 5.2) was measured relative to the intrinsic solubility in buffer. Large increases in SER were observed in both lamellar (10-2000 fold) and cubic (10-30,000 fold) liquid crystal phases. Positive correlations were observed between the solubilization benefit provided by each phase and drug lipophilicity (r(2) > or = 0.9). These phase/solubility trends assist in our understanding of the mechanism by which poorly water-soluble drugs are trafficked across the intestinal colloidal species that form during the digestion of lipid-based drug delivery systems.