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Influence of DOPC on Lipid Liquid Crystalline Sponge Phases

Mc Evoy, Aina LU (2021) KEMR20 20211
Department of Chemistry
Theoretical Chemistry
Abstract
Lipids in the presence of a solvent can through the process of self-assembly form a number of phases referred to as Lipid Liquid Crystalline (LLC) phases. The inverse hexagonal, inverse bicontinuous cubic phases and sponge phase are examples of LLC structures that have been studied and used in drug delivery settings or food applications. For this project the focal point will be the sponge (L3) phase. This structure is formed in the presence of water and contains a network of hydrophilic water channels and continuous hydrophobic bilayer structures, similar to the inverse bicontinuous cubic LLC phase. However, the sponge phase tends to have a greater flexibility and fluid nature compared to the inverse bicontinuous cubic phase allowing for... (More)
Lipids in the presence of a solvent can through the process of self-assembly form a number of phases referred to as Lipid Liquid Crystalline (LLC) phases. The inverse hexagonal, inverse bicontinuous cubic phases and sponge phase are examples of LLC structures that have been studied and used in drug delivery settings or food applications. For this project the focal point will be the sponge (L3) phase. This structure is formed in the presence of water and contains a network of hydrophilic water channels and continuous hydrophobic bilayer structures, similar to the inverse bicontinuous cubic LLC phase. However, the sponge phase tends to have a greater flexibility and fluid nature compared to the inverse bicontinuous cubic phase allowing for improved swelling properties. Where water channel diameters of 12 nm for the sponge phase compared to 8.4 nm for the inverse bicontinuous cubic phase have been observed for similar systems. These structural features could allow the lipid sponge phase to accommodate larger molecules. The water channel and bilayers of the structure construct the polar and apolar regions of the structure respectively. The presence of these two regions together with the ability to swell are greatly sought after properties in drug delivery structures. It has previously been observed that the glycerides: Capmul glycerol monooleate (GMO-50) and diglycerol monooleate (DGMO), when mixed within a certain range of ratios form a sponge phase when hydrated. It was also found that the addition of an emulsifier Polysorbate 80 (P80) expands this sponge forming range. In this thesis the effect of the zwitterionic phospholipid dioleoylphosphatidylcholine (DOPC) on sponge phases will be investigated. The incorporation of charges from the zwitterionic head group of DOPC to the system may be of interest when it comes to drug uptake and releasing mechanisms. Specifically the thesis investigates the effect of adding DOPC to GMO-50/DGMO and GMO-50/DGMO/P80 mixtures that are in or around their sponge phase forming ratios. Also the thesis investigates the possibility of replacing DGMO with DOPC without affecting the original phase present. The phases formed by these various mixtures were identified by visual inspection with cross polarised light as well as by small angle X-ray scattering (SAXS) measurements. It was found that the GMO-50/DGMO/P80/water sponge forming system tolerated the inclusion of DOPC to a greater extent compared to the GMO-50/DGMO/water system. This was observed for both the addition of DOPC as well as the replacement of DGMO with DOPC. However, where DGMO had been fully replaced by DOPC none of the systems studied formed a pure sponge phase at 25°C. The temperature dependencies of the formed phases were also investigated for the hydrated GMO-50/DGMO/DOPC(/P80) systems, showing different behaviours depending on the DOPC concentration in the system. (Less)
Popular Abstract
Lipids are the building blocks for many biological systems, such as cell membranes. Some lipids are described as being amphiphilic meaning that they consist of both water-loving (hydrophilic) and water-disliking (hy- drophobic) parts. The hydrophobic part comprises one or more hydrocarbon tails or chains and the hy- drophilic part comprises the head group. In the presence of a solvent, such as water, due to the amphiphilic nature of the lipids they try find the optimum physical formation for that environment, in order to minimise the exposure of the hydrophobic part of the lipid to water. This process or ordering event is called lipid self-assembly, and is dependant on many factors such as the characteristics of the lipid as well as... (More)
Lipids are the building blocks for many biological systems, such as cell membranes. Some lipids are described as being amphiphilic meaning that they consist of both water-loving (hydrophilic) and water-disliking (hy- drophobic) parts. The hydrophobic part comprises one or more hydrocarbon tails or chains and the hy- drophilic part comprises the head group. In the presence of a solvent, such as water, due to the amphiphilic nature of the lipids they try find the optimum physical formation for that environment, in order to minimise the exposure of the hydrophobic part of the lipid to water. This process or ordering event is called lipid self-assembly, and is dependant on many factors such as the characteristics of the lipid as well as environmen- tal factors. The self-assembly may result in the formation of structures or so called Lipid liquid crystalline phases. Some of these structures are used for drug delivery where the structure contains a medical substance which is carried to its target. Some Lipid liquid crystalline phases form structures with hydrophobic regions and hydrophilic compartments, which is desirable as the structure can incorporate both hydrophobic and hy- drophilic medical substances. In this project the main focus will be on one particular Lipid liquid crystalline phase, namely the sponge phase. This phase has the property of both having hydrophobic and hydrophilic continuous networks, but also a flexibility which allows for swelling of the system. Larger water channels are useful for the purpose of drug delivery, as larger substances can also be incorporated. In this study the sponge phase consisting of a mixture of two and three lipid compounds that have previously been shown to form sponge phases at certain ratios once hydrated. The lipids used were the glycerides: Capmul glycerol monooleate (GMO-50) and diglycerol monooleate (DGMO) both in the presence and absence of an emulsifier Polysorbate 80 (P80) which is commonly used in drug and food applications. In this project these systems will be further investigated and modified by the addition of another lipid namely dioleoylphosphatidylcholine (DOPC) and also by replacement of DGMO with DOPC. DOPC compared to DGMO has the property of having two hydrocarbon tails as opposed to one and a zwitterionic head group. The latter means that it has a locally positive and negative charged head group, which could possibly contribute beneficial drug delivery properties. Through this study it was found that the presence of P80 enhances the retention of the sponge phase as the relative proportion of lipids (GMO-50/DGMO/DOPC) changed. However, fully replacing the DGMO portion of a lipid ratio with DOPC, at 25°C, altered the phase formed and did not reproduce the phase of the original system. (Less)
Please use this url to cite or link to this publication:
author
Mc Evoy, Aina LU
supervisor
organization
course
KEMR20 20211
year
type
H2 - Master's Degree (Two Years)
subject
keywords
Lipid liquid crystalline phases, Sponge phases, DOPC, SAXS, Theoretical chemistry
language
English
id
9060229
date added to LUP
2021-07-01 15:33:26
date last changed
2021-07-01 15:33:26
@misc{9060229,
  abstract     = {{Lipids in the presence of a solvent can through the process of self-assembly form a number of phases referred to as Lipid Liquid Crystalline (LLC) phases. The inverse hexagonal, inverse bicontinuous cubic phases and sponge phase are examples of LLC structures that have been studied and used in drug delivery settings or food applications. For this project the focal point will be the sponge (L3) phase. This structure is formed in the presence of water and contains a network of hydrophilic water channels and continuous hydrophobic bilayer structures, similar to the inverse bicontinuous cubic LLC phase. However, the sponge phase tends to have a greater flexibility and fluid nature compared to the inverse bicontinuous cubic phase allowing for improved swelling properties. Where water channel diameters of 12 nm for the sponge phase compared to 8.4 nm for the inverse bicontinuous cubic phase have been observed for similar systems. These structural features could allow the lipid sponge phase to accommodate larger molecules. The water channel and bilayers of the structure construct the polar and apolar regions of the structure respectively. The presence of these two regions together with the ability to swell are greatly sought after properties in drug delivery structures. It has previously been observed that the glycerides: Capmul glycerol monooleate (GMO-50) and diglycerol monooleate (DGMO), when mixed within a certain range of ratios form a sponge phase when hydrated. It was also found that the addition of an emulsifier Polysorbate 80 (P80) expands this sponge forming range. In this thesis the effect of the zwitterionic phospholipid dioleoylphosphatidylcholine (DOPC) on sponge phases will be investigated. The incorporation of charges from the zwitterionic head group of DOPC to the system may be of interest when it comes to drug uptake and releasing mechanisms. Specifically the thesis investigates the effect of adding DOPC to GMO-50/DGMO and GMO-50/DGMO/P80 mixtures that are in or around their sponge phase forming ratios. Also the thesis investigates the possibility of replacing DGMO with DOPC without affecting the original phase present. The phases formed by these various mixtures were identified by visual inspection with cross polarised light as well as by small angle X-ray scattering (SAXS) measurements. It was found that the GMO-50/DGMO/P80/water sponge forming system tolerated the inclusion of DOPC to a greater extent compared to the GMO-50/DGMO/water system. This was observed for both the addition of DOPC as well as the replacement of DGMO with DOPC. However, where DGMO had been fully replaced by DOPC none of the systems studied formed a pure sponge phase at 25°C. The temperature dependencies of the formed phases were also investigated for the hydrated GMO-50/DGMO/DOPC(/P80) systems, showing different behaviours depending on the DOPC concentration in the system.}},
  author       = {{Mc Evoy, Aina}},
  language     = {{eng}},
  note         = {{Student Paper}},
  title        = {{Influence of DOPC on Lipid Liquid Crystalline Sponge Phases}},
  year         = {{2021}},
}