This paper describes how we have used material science, physical chemistry, and some luck, to design a new thermal-sensitive liposome (the low temperature sensitive liposome (LTSL)) that responds at clinically attainable hyperthermic temperatures releasing its drug in a matter of seconds as it passes through the microvasculature of a warmed tumor. The LTSL is composed of a judicial combination of three component lipids, each with a specific function and each affecting specific material properties, including a sharp thermal transition and a rapid on-set of membrane permeability to small ions, drugs and small dextran polymers. Experimentally, the paper describes how bilayer-concentration changes involving the lysolipid and the presence or absence of DSPE-PEG2000 affect both the lipid transition temperature and the drug release. While the inclusion of 4 mol% DSPE-PEG2000 raises the transition temperature peak (T(m)) by about 1 degrees C, the inclusion of 5.0, 9.7, 12.7 and 18.0 mol% MSPC slightly lowered this peak back to 41.7 degrees C, while not further broadening the peak breadth. As for drug release, in the absence of MSPC, the encapsulated doxorubicin-citrate is hardly released at all. Increasing the composition of MSPC in the lipid mixture (5.0, 7.4, 8.5 and 9.3 mol% MSPC) shows faster and faster initial doxorubicin release rates, with 8.5 and 9.3 mol% MSPC formulations giving 80% of encapsulated drug released in 4 and 3 min, respectively. The Thermodox formulation (9.7 mol% MSPC) gives 60% released in the first 20 s. The presence of PEG-lipid is found to be essential in order for the lysolipid-induced permeability to reach these very fast times. From drug and dextran release experiments, and estimates of the molecular and pore size, the conclusions are that: in order to induce lasting nanopores in lipid bilayers -10 nm diameter, they initially require the presence (from the solid phase structure) of grain boundary defects at the DPPC transition and the permeabilizing component(s) can either be a pore forming lysolipid/surfactant plus a PEG-lipid, or can be generated by a PEG-surfactant incorporated at -4-5 mol%. The final discussion is centered around the postulated defect structures that result in membrane leakage and the permeability of doxorubicin and H+ ions.
Digital Image Correlation (DIC) is employed for the measurement of full-field deformation during fluid-structure interaction experiments in a wind tunnel. The methodology developed for the wind tunnel environment is quantitatively assessed. The static deformation error of the system is shown to be less than 0.8% when applied to a curved aerofoil specimen moved through known displacements using a micrometer. Enclosed camera fairings were shown to be required to minimise error due to wind induced camera vibration under aerodynamic loading. The methodology was demonstrated using a high performance curved foil, from a NACRA F20 sailing catamaran, tested within the University of Southampton RJ Mitchell, 3.5m x 2.4m, wind tunnel. The aerodynamic forces induced in the wind tunnel are relatively small, compared with typical hydrodynamic loading, resulting in small deformations. The coupled deflection and blade twist is evaluated over the tip region (80-100% Span, measured from the root) for a range of wind speeds and angles of attack. Steady deformations at low angles of attack were shown to be well captured however unsteady deformations at higher angles of attack were observed as an increase in variability due to hardware limitations in the current DIC system. It is concluded that higher DIC sample rates are required to assess unsteady deformations in the future. The full field deformation data reveals limited blade twist for low angles of attack, below the stall angle. For larger angles, however, there is a tendency to reduce the effective angle of attack at the tip of the structure, combined with an unsteady structural response. This capability highlights the benefits of the presented methodology over fixed-point measurements as the three dimensional foil deflections can be assessed over a large tip region. In addition, the methodology demonstrates that very small deformations and twist angles can be resolved.
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