Investigating the role of cholesterol in the formation of non-ionic surfactant based bilayer vesicles: thermal analysis and molecular dynamics

Jitinder S. Wilkhu, Defang Ouyang, Marc J. Kirchmeier, David E Anderson, Yvonne Perrie

Research output: Contribution to journalArticle

14 Citations (Scopus)

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.

LanguageEnglish
Pages331-41
Number of pages11
JournalInternational Journal of Pharmaceutics
Volume461
Issue number1-2
DOIs
Publication statusPublished - 30 Jan 2014

Fingerprint

Molecular Dynamics Simulation
Surface-Active Agents
Glycerol
Liposomes
Hot Temperature
Cholesterol
Temperature
Weights and Measures
Differential Scanning Calorimetry
Thermodynamics
Freezing
Microscopy
cholesteryl phosphate
dicetylphosphate
Research

Keywords

  • differential scanning calorimery
  • pharmaceutical chemistry
  • cholesterol
  • drug stability
  • glycerides
  • liposomes
  • microscopy
  • molecular dynamics simulation
  • organophosphates
  • surface-active agents
  • temperature
  • thermodynamics
  • thermogravimetry
  • time Factors
  • transition Temperature
  • niosomes
  • monolayer
  • particle size
  • surface change
  • molecular dynamics

Cite this

@article{b5f52f98722c4867a34731ab6fc9ca39,
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.",
keywords = "differential scanning calorimery, pharmaceutical chemistry, cholesterol, drug stability, glycerides, liposomes, microscopy, molecular dynamics simulation, organophosphates, surface-active agents, temperature, thermodynamics, thermogravimetry, time Factors, transition Temperature, niosomes, monolayer, particle size, surface change, molecular dynamics",
author = "Wilkhu, {Jitinder S.} and Defang Ouyang and Kirchmeier, {Marc J.} and Anderson, {David E} and Yvonne Perrie",
note = "Copyright {\circledC} 2013 Elsevier B.V. All rights reserved.",
year = "2014",
month = "1",
day = "30",
doi = "10.1016/j.ijpharm.2013.11.063",
language = "English",
volume = "461",
pages = "331--41",
journal = "International Journal of Pharmaceutics",
issn = "0378-5173",
number = "1-2",

}

Investigating the role of cholesterol in the formation of non-ionic surfactant based bilayer vesicles : thermal analysis and molecular dynamics. / Wilkhu, Jitinder S.; Ouyang, Defang; Kirchmeier, Marc J.; Anderson, David E; Perrie, Yvonne.

In: International Journal of Pharmaceutics, Vol. 461, No. 1-2, 30.01.2014, p. 331-41.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Investigating the role of cholesterol in the formation of non-ionic surfactant based bilayer vesicles

T2 - International Journal of Pharmaceutics

AU - Wilkhu, Jitinder S.

AU - Ouyang, Defang

AU - Kirchmeier, Marc J.

AU - Anderson, David E

AU - Perrie, Yvonne

N1 - Copyright © 2013 Elsevier B.V. All rights reserved.

PY - 2014/1/30

Y1 - 2014/1/30

N2 - 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.

AB - 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.

KW - differential scanning calorimery

KW - pharmaceutical chemistry

KW - cholesterol

KW - drug stability

KW - glycerides

KW - liposomes

KW - microscopy

KW - molecular dynamics simulation

KW - organophosphates

KW - surface-active agents

KW - temperature

KW - thermodynamics

KW - thermogravimetry

KW - time Factors

KW - transition Temperature

KW - niosomes

KW - monolayer

KW - particle size

KW - surface change

KW - molecular dynamics

UR - http://www.sciencedirect.com/science/journal/03785173

U2 - 10.1016/j.ijpharm.2013.11.063

DO - 10.1016/j.ijpharm.2013.11.063

M3 - Article

VL - 461

SP - 331

EP - 341

JO - International Journal of Pharmaceutics

JF - International Journal of Pharmaceutics

SN - 0378-5173

IS - 1-2

ER -