The aim of this research was to investigate the molecular interactions occurring in the formulation of non-ionic surfactant based vesicles composed monopalmitoyl glycerol (MPG), cholesterol (Chol) and dicetyl phosphate (DCP). In the formulation of these vesicles, the thermodynamic attributes and surfactant interactions based on molecular dynamics, Langmuir monolayer studies, differential scanning calorimetry (DSC), hot stage microscopy and thermogravimetric analysis (TGA) were investigated. Initially the melting points of the components individually, and combined at a 5:4:1 MPG:Chol:DCP weight ratio, were investigated; the results show that lower (90 C) than previously reported (120-140 C) temperatures could be adopted to produce molten surfactants for the production of niosomes. This was advantageous for surfactant stability; whilst TGA studies show that the individual components were stable to above 200 C, the 5:4:1 MPG:Chol:DCP mixture show ∼2% surfactant degradation at 140 C, compared to 0.01% was measured at 90 C. Niosomes formed at this lower temperature offered comparable characteristics to vesicles prepared using higher temperatures commonly reported in literature. In the formation of niosome vesicles, cholesterol also played a key role. Langmuir monolayer studies demonstrated that intercalation of cholesterol in the monolayer did not occur in the MPG:Chol:DCP (5:4:1 weight ratio) mixture. This suggests cholesterol may support bilayer assembly, with molecular simulation studies also demonstrating that vesicles cannot be built without the addition of cholesterol, with higher concentrations of cholesterol (5:4:1 vs 5:2:1, MPG:Chol:DCP) decreasing the time required for niosome assembly. © 2013 Elsevier B.V.
|Number of pages||11|
|Journal||International Journal of Pharmaceutics|
|Publication status||Published - 30 Jan 2014|
Bibliographical noteNOTICE: this is the author’s version of a work that was accepted for publication in International journal of pharmaceutics. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Wilkhu, JS, Ouyang, D, Kirchmeier, MJ, Anderson, DE & Perrie, Y, 'Investigating the role of cholesterol in the formation of non-ionic surfactant based bilayer vesicles: Thermal analysis and molecular dynamics' International journal of pharmaceutics, vol. 461, no. 1-2(2014) DOI http://dx.doi.org/10.1016/j.ijpharm.2013.11.063
Funding: BBSRC (Industrial Case Award) [BB/G017948/1]; Variation Biotechnologies Inc
- particle size
- surface charge
- molecular dynamics
- differential scanning calorimetry
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Non-ionic surfactant technology for the delivery and administration of sub-unit flu antigensAuthor: Wilkhu, J., 12 Jun 2013
Supervisor: Perrie, Y. (Supervisor) & Mohammed, A. (Supervisor)
Student thesis: Doctoral Thesis › Doctor of PhilosophyFile