Scattering Solutions proposes to develop the new non-invasive technique of Surface Light Scattering Spectroscopy (SLSS) to characterize interfaces between fluids, with special initial emphasis on the quantitative properties of biomembranes with respect to drug permeability. SLSS technology promises a distinct advantage over current methods for pharmacokinetics screening of drug candidates: the ability to quickly and accurately measure key biophysical characteristics and behavior of complex interfaces without physical disturbance. In addition to liquid/vapor interfaces, the method is directly applicable to measurement of lipid mono-and bilayers spread over open surfaces and between polar and non-polar liquids. Successful development of this approach will contribute to reducing the high cost of ADMET (Absorption, Distribution, Metabolism, Excretion and Toxicology) drug screening. Scattering Solutions personnel have been instrumental in developing new approaches and techniques that overcome traditional obstacles, such as vibration and meniscus effects, which now make SLSS commercially feasible. Technical details of the SLSS method and how it may be simply developed and applied to measure formerly inaccessible quantities are discussed. Preliminary experimental results confirming the validity of our techniques are shown for simple interfaces and lipid monolayers. An interdisciplinary team has been formed to assess the feasibility of employing SLSS for lipid characterization and to examine technical issues and refinements needed for robust and accurate determination of biomembrane properties. Phase I uses a laboratory instrument to obtain measurements that can be verified against published literature, including compounds that are of interest to blood-brain barrier studies. Phase II includes refinement and generalization of an advanced instrument design, fabrication and testing of a commercial prototype, measurement of various fluid interface configurations that better approximate in vivo conditions, examination of different measurement strategies, and extension of the preliminary measurements to a wider range of compounds of deep interest and concern in the pharmaceutical and medical industries. It should also result in an innovative and practical instrument for non-contact studies of biomembranes and their models in general. ? Project Narrative:Surface light scattering spectroscopy is an inexpensive alternative to conventional methods which can measure drug permeation through biomembranes, and it holds the potential for more accurate early and late stage high throughput ADMET drug screening. The success of this project could result in accelerating drug development and lowering the cost of bringing drugs to market. ? ? ?
