Topics Covered
Background
Determination of Zeta Potential and Particle
Size
The Importance of Zeta Potential to
Liposomes
Uptake of Liposomes by the Body
The Effect Hydrophilic Polymers on
Liposomes
Case Study – Zeta
Potential Study of The Effect of Polyethylene Glycol on Liposomes
Experimental
Results
Conclusions
Background
Liposomes are vesicles in which an aqueous
volume is entirely enclosed by a membrane composed of lipid molecules, usually
phospholipid. They can be prepared so that they entrap materials both within
their aqueous compartment (water-soluble materials) and within the membrane
(oil-soluble materials). They are extensively used as vehicles for the targeted
delivery of drugs. The fate of intravenously injected liposomes is determined by
a number of properties. Two of the most important are particle size and zeta
potential.
Determination of Zeta
Potential and Particle Size
The zeta potential is the overall charge a
particle acquires in a particular medium. Both size and zeta potential can be
measured on a Zetasizer 3000HSA.
The Importance of Zeta
Potential to Liposomes
Knowledge of the zeta potential of a
liposome preparation can help to predict the fate of the liposomes in vivo. Any
subsequent modification of the liposome surface can also be monitored by
measurement of the zeta potential.
Uptake of Liposomes by the
Body
A major problem in the use of liposomes for
the delivery of drugs by injection into the blood stream is the specific uptake
of the liposomes by the reticuloendothelial system (RES). Longer circulation
times can be achieved by coating the liposomes with a suitable polymer.
Liposomes that lengthen circulation times in the blood and avoid uptake by the
RES are called Stealth liposomes (Stealth is a registered trademark of Liposome
Technology Inc., Menlo
Park, CA).
The Effect Hydrophilic
Polymers on Liposomes
The presence of hydrophilic polymers on the
surface of the liposomes gives rise to a steric barrier which inhibits the
adsorption of blood components which assist in the uptake of the liposomes by
the RES.
The most successful hydrophilic polymers to
date are polyethylene glycols (PEG). Figure 1 is schematic showing a liposome
with covalently attached polyethylene glycol on the surface.
Figure 1. Schematic diagram of a polymer
coated liposome.
Case Study – Zeta Potential Study
of The Effect of Polyethylene Glycol on Liposomes
This application note describes zeta
potential measurements of liposomes with polyethylene glycol covalently attached
onto the surface.
Experimental
Anionic liposomes were prepared which
contained a polyethylene glycol (PEG) derivatized phospholipid at different
concentrations.The polyethylene glycol had a molecular weight of 2000
Daltons. The zeta
potentials of these liposome preparations were measured using a Malvern Zetasizer 3000HSA in saline at physiological
concentration.
Results
Figure 2 shows a plot of the measured zeta
potential of liposomes as a function of the concentration of PEG derivatized
phospholipid (mole %). The zeta potential of ‘naked’ liposomes (with no PEG
present on the liposome surface) is –43mV.The zeta potential starts to decrease
with increasing concentration of PEG derivatized phospholipid and eventually
reaches a plateau around –5mV. The decrease in the zeta potential as the surface
of the liposome is covered can be explained in one of two ways:
- The slipping plane being moved further
away from the liposome surface and hence reducing the zeta potential,
- The drag caused by the presence of the PEG
chains on the liposome surface reducing the mobility of the liposomes (and hence
the zeta potential).
Figure 2. The zeta potential as a
function of the mole % PEG derivatized phospholipid liposomes in saline at
physiological concentration.
The plateau region observed in figure 2
corresponds to the point at which no more PEG molecules can fit around the
surface of the liposome. In the data shown in figure 2, this point occurs at a
concentration of 5 mole % of PEG derivatized phospholipid.
The measurements also show that samples in
physiological strength saline can be easily measured in the Malvern Zetasizer 3000HSA.
Conclusions
The surface characteristics of steric
stabilised liposomes are determined by both the molecular mass of the PEG and
the amount of the PEG derivatized phospholipid incorporated into the lipid
bilayer. Such surface characteristics of liposomes can be investigated by
measurement of the zeta potential.
Source: "The Use of Zeta Potential Measurements to Study
Sterically Stabilized Liposomes”, Application Note by
Malvern Instruments.
For more information on this source please
visit Malvern
Instruments Ltd (UK) or Malvern Instruments
(USA).