Delaram Ahmadi1, Ruth Ledder2, Najet Mahmoudi3, Peixun Li3, James Tellam3, Douglas Robinson3, Richard K Heenan3, Paul Smith4, Christian D Lorenz4, David J Barlow5, M Jayne Lawrence6. 1. Institute of Pharmaceutical Science, King's College London, Franklin Wilkins Building, 150 Stamford Street, London SE1 9NH, United Kingdom. 2. Division of Pharmacy & Optometry, School of Health Sciences, Stopford Building, University of Manchester, Oxford Road, Manchester M13 9PG, United Kingdom. 3. STFC ISIS Facility, Rutherford Appleton Laboratory, Chilton, Didcot OX11 0QX, United Kingdom. 4. Department of Physics, King's College London, London WC2R 2LS, United Kingdom. 5. Institute of Pharmaceutical Science, King's College London, Franklin Wilkins Building, 150 Stamford Street, London SE1 9NH, United Kingdom; Division of Pharmacy & Optometry, School of Health Sciences, Stopford Building, University of Manchester, Oxford Road, Manchester M13 9PG, United Kingdom. Electronic address: dave.barlow@kcl.ac.uk. 6. Division of Pharmacy & Optometry, School of Health Sciences, Stopford Building, University of Manchester, Oxford Road, Manchester M13 9PG, United Kingdom. Electronic address: jayne.lawrence@manchester.ac.uk.
Abstract
HYPOTHESIS: Biomimetic liquid crystalline systems are widely used in skin care cosmetics and topical pharmaceutical preparations. Our ability to rationally design such formulations, however, is hampered by our incomplete understanding of their structure on the nanoscale. EXPERIMENTS: Using polarized light microscopy and small-angle and wide-angle X-ray scattering, the molecular architecture and properties of a barrier formulation prepared from distearoylphosphatidylcholine mixed with long chain fatty acid and alcohols, with and without antimicrobial pentanediols are directly probed. The nature and composition of the phases identified are determined through small-angle neutron scattering studies using chain-deuterated components, and the detailed structure and dynamics of the gel network lamellae are determined through molecular dynamics simulations. FINDINGS: The formulations show molecular ordering with long and short periodicity lamellar phases and there is little change in these structures caused by changes in temperature, drying, or the application of shear stress. The diol-free formulation is demonstrated to be self-preserving, and the added pentanediols are shown to distribute within the interlamellar regions where they limit availability of water for microbial growth. In culmination of these studies, we develop a more complete picture of these complex biomimetic preparations, and thereby enable their structure-based design.
HYPOTHESIS: Biomimetic liquid crystalline systems are widely used in skin care cosmetics and topical pharmaceutical preparations. Our ability to rationally design such formulations, however, is hampered by our incomplete understanding of their structure on the nanoscale. EXPERIMENTS: Using polarized light microscopy and small-angle and wide-angle X-ray scattering, the molecular architecture and properties of a barrier formulation prepared from distearoylphosphatidylcholine mixed with long chain fatty acid and alcohols, with and without antimicrobial pentanediols are directly probed. The nature and composition of the phases identified are determined through small-angle neutron scattering studies using chain-deuterated components, and the detailed structure and dynamics of the gel network lamellae are determined through molecular dynamics simulations. FINDINGS: The formulations show molecular ordering with long and short periodicity lamellar phases and there is little change in these structures caused by changes in temperature, drying, or the application of shear stress. The diol-free formulation is demonstrated to be self-preserving, and the added pentanediols are shown to distribute within the interlamellar regions where they limit availability of water for microbial growth. In culmination of these studies, we develop a more complete picture of these complex biomimetic preparations, and thereby enable their structure-based design.