title: Investigating the role of cholesterol in the formation of non-ionic surfactant based bilayer vesicles: thermal analysis and molecular dynamics.
abstract: 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.
authors: School of Life and Health Sciences, Aston University, Birmingham B4 7ET, UK.
authors: Jitinder S
authors: JS
authors: Wilkhu
authors: School of Life and Health Sciences, Aston University, Birmingham B4 7ET, UK.
authors: Defang
authors: D
authors: Ouyang
authors: Variation Biotechnologies, 222 Third Street, Suite 2241, Cambridge, MA 02142, USA.
authors: Marc J
authors: MJ
authors: Kirchmeier
authors: Variation Biotechnologies, 222 Third Street, Suite 2241, Cambridge, MA 02142, USA.
authors: David E
authors: DE
authors: Anderson
authors: School of Life and Health Sciences, Aston University, Birmingham B4 7ET, UK. Electronic address: y.perrie@aston.ac.uk.
authors: Yvonne
authors: Y
authors: Perrie
mesh_terms: D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical / Q000379:methods; D002784:Cholesterol / Q000737:chemistry*; D004355:Drug Stability; D005989:Glycerides / Q000737:chemistry*; D008081:Liposomes; D008853:Microscopy; D056004:Molecular Dynamics Simulation; D010755:Organophosphates / Q000737:chemistry*; D013501:Surface-Active Agents / Q000737:chemistry*; D013696:Temperature; D013816:Thermodynamics; D013818:Thermogravimetry; D013997:Time Factors; D044366:Transition Temperature
chemical_list: D005989:Glycerides; D008081:Liposomes; D010755:Organophosphates; D013501:Surface-Active Agents; C002290:dicetylphosphate; D002784:Cholesterol; C027735:palmitoyl glycerol
keywords: Differential scanning calorimetry; Molecular dynamics; Monolayer; Niosomes; Particle size; Surface charge