Extensive surface studies help to analyse zeta potential data: the case of cationic emulsions
Introduction
Emulsions are widely used in pharmaceutical practice as they allow to entrap large doses of lipophilic substances. They are convenient for all routes of administration (Benita, 1999, Klang et al., 1994, Stevenson et al., 2000), they decrease inter and intra-individual absorption variations when given orally (Gershanik and Benita, 2000), they are stable (Min-Woo et al., 2001), can be easily sterilised (Groves and Herman, 1993) and have a relatively low cost of production.
More recently, cationic emulsions have received increased attention as potential drug delivery systems as they succeeded to show improved electrostatically-induced stability and enhanced in vivo absorption, probably due to the increased interactions with the biological membranes (Gershanik et al., 2000, Yang and Benita, 2000). In addition, they permit to condense negatively charged macromolecules as DNA or oligonucleotides (Kim et al., 2003, Teixeira et al., 2001, Teixeira et al., 2003).
In this context emulsions containing triglycerides as the oil phase, phospholipids (PL) and Poloxamer as emulsifiers and a lipophilic cation such as stearylamine (SA) or oleylamine (OA) are developed as potential drug carriers (Benita, 1999, Pongcharoenkiat et al., 2002, Yang and Benita, 2000). The influence of the amine on the emulsions characteristics is therefore an essential aspect for this technology, as it was demonstrated that the surface charge might affect physical and chemical stability (Grit and Crommelin, 1993, Zuidam and Crommelin, 1995) and future encapsulation of active molecules (Pongcharoenkiat et al., 2002).
This is the reason why it was urgent to examine the effects of increasing amounts of cationic lipid on the electrostatic properties of the emulsion surface. Surprisingly, only a few papers deal with surface properties in cationic emulsions (Kim et al., 2003, Min-Woo et al., 2001, Pongcharoenkiat et al., 2002, Teixeira et al., 2001), most of them limiting their research to ζ-potential measurements and none of them presenting a complete analysis of the issue in respect to the cation concentration. More sophisticated studies were performed only in liposomes (Meidan et al., 2000, Zuidam and Barenholz, 1997). While standard ζ-potential measures are usually satisfactory for industrial purposes, they are far from being adequate for a full comprehension of the surface.
The aim of this study was therefore to investigate and fully evaluate the effect of increasing amounts of the cationic lipid oleylamine in the electrostatic properties of the emulsion. In order to perform such investigation, experimental methods existing previously for liposomes were adapted to our system and new approaches have been developed. These tools allowed us to achieve a comprehensive analysis of the ζ-potential data discriminating between surface saturation, ionisation saturation and shear plane shift effects.
Section snippets
Materials
Oleylamine was developed conjointly by Novagali and Sigma. It was synthesised from vegetal oleic acid and contained at least 85% oleylamine (95% total primary amines content), in contrast to the commercially available one which contains 98% total primary amines but among which only 70% are oleylamine.
Lipoid E-80 was purchased from Lipoid Gmbh (Ludwigshafen, Germany). According to the manufacturer, the mixture is composed of 80% phosphatidylcholine (PC), 8% phosphatidylethanolamine (PE) and 3%
Size and ζ-potential
The mean droplet diameter of the emulsions was not affected by the OA content and varied from 140 to160 nm showing an unimodal distribution (polydispersity index: <0.2), while the SUV liposomes displayed average vesicle diameters of 50 nm (polydispersity index: ∼0.6) whatever their OA content (data not shown).
The ζ-potential values of the emulsions with increasing OA content were investigated in Hepes 20 mM pH 7.4. As shown in Fig. 1, the non-cationic emulsion displayed a negative potential near
Discussion
The electrokinetic or ζ-potential is defined as the average electrostatic potential existing at the hydrodynamic plane of shear, somewhere between the Stern plane and the end of the diffuse layer and normally considered to be 0.2 nm from the surface (Cevc, 1990, Eisenberg et al., 1979, Kraayenhof et al., 1996). This concept imposes the definition of the surface plane, which is still ambiguous in the majority of papers dealing with surface properties in lipid model membranes. Indeed the
Conclusion
In this paper, new approaches and modified methods for the characterisation of charged colloids in general and cationic emulsion surface in particular are presented. This study demonstrates the complexity in analysing ζ-potential data and the difficulty in relating it to the cation concentration since phenomena such as surface saturation, ionisation decrease, ion condensation and slipping plane thickness are playing a major role.
With OA containing emulsions up to a OA:PL ratio of 0.67, it was
Acknowledgements
We thank the Association Nationale de la Recherche Technique (ANRT) for supporting Laura Rabinovich-Guilatt with a CIFRE convention. The authors acknowledge professor Yechezkel Barenholz from the Hebrew University of Jerusalem (Israel), Dr. Franck Artzner and Prof. Dominique Langevin from the Université Paris Sud (France) for fructiferous discussions.
References (45)
Examination of the intracellular ionic environment and of ionophore action by null point measurements employing the fluorescein chromophore
J. Biol. Chem.
(1983)Prevention of topical and ocular oxidative stress by positively charged submicron emulsion
Biomed. Pharmacother.
(1999)Membrane electrostatics
Biochim. Biophys. Acta
(1990)- et al.
Self-dispersing lipid formulations for improving oral absorption of lipophilic drugs
Eur. J. Pharm. Biopharm.
(2000) - et al.
Charge-dependent interaction of self-emulsifying oil formulations with Caco-2 cells monolayers: binding, effects on barrier function and cytotoxicity
Int. J. Pharm.
(2000) - et al.
The effect of surface charge on the hydrolysis kinetics of partially hydrogenated egg phosphatidylcholine and egg phosphatidylglycerol in aqueous liposome dispersions
Biochim. Biophys. Acta
(1993) - et al.
External surface and lamellarity of lipid vesicles: a practice-oriented set of assay methods
Biochim. Biophys. Acta
(1994) - et al.
Transbilayer diffusion of phospholipids: dependence on headgroup structure and acyl chain length
Biochim. Biophys. Acta
(1988) - et al.
The location of fluorescence probes with charged groups in model membranes
Biochim. Biophys. Acta
(1998) - et al.
The effects of serum on the stability and the transfection activity of the cationic lipid emulsion with various oils
Int. J. Pharm.
(2003)
Addition of (tri-)block copolymers to phospholipid vesicles: a study of the molecular morphology and structure by using hydrophobic dye molecules as bilayer probes
J. Colloid Interface Sci.
Monovalent cations differentially affect membrane surface properties and membrane curvature, as revealed by fluorescent probes and dynamic light scattering
Biochim. Biophys. Acta
Interactions of a non-ionic surfactant with mixed phospholipid-oleic acid monolayers. Studies under dynamic conditions
Colloids Surf.
Interaction of oligonucleotides with cationic lipids: the relationship between electrostatics, hydration and state of aggregation
Biochim. Biophys. Acta
A simple expression for Henry’s function for the retardation effect in electrophoresis of spherical colloidal particles
J. Colloid Interface Sci.
The effect of surface charge and partition coefficient on the chemical stability of solutes in O/W emulsions
J. Pharm. Sci.
A NMR study of the ionisation of fatty acids, fatty amines and N-acylamino acids incorporated in phosphatidylcholine vesicles
Biochim. Biophys. Acta
Efficacy and safety of cyclosporin A ophthalmic emulsion in the treatment of moderate-to-severe dry eye disease: a dose-ranging, randomized trial. The Cyclosporin A Phase 2 Study Group
Ophthalmology
Cationic emulsions improves the delivery of oligonucleotides to leukemic P388/ADR cells in ascite
J. Controlled Release
Characterisation of oligonucleotide/lipid interactions in submicron cationic emulsions: influence of the cationic lipid structure and the presence of PEG-lipids
Biophys. Chem.
Determination by photoreduction of flip-flop kinetics of spin-labeled stearic acids across phospholipid bilayers
Biochim. Biophys. Acta
Electrostatic parameters of cationic liposomes commonly used for gene delivery as determined by 4-heptadecyl-7-hydroxycoumarin
Biochim. Biophys. Acta
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