Lipids and surfactants

It should be noted that Cypridina luciferin emits a fairly strong chemiluminescence in aqueous solutions in the presence of various lipids and surfactants, even in the complete absence of luciferase. The luminescence is especially conspicuous with cationic surfactants (such as hexadecyltrimethylammonium bromide) and certain emulsion materials (such as egg yolk and mayonnaise). Certain metal ions (especially Fe2+) and peroxides can also cause luminescence of the luciferin. Therefore, great care must be taken in the detection of Cypridina luciferase in biological samples with Cypridina luciferin. 

The solid matrix of SLN protects the drug from hydrolysis and oxidation. Chemical stability of tocopherol and retinol improves considerably [17,39], with tocopherol improving by 57% compared with an aqueous dispersion. The degree of retinol stabilization depends on the nature of lipid and surfactant [39]. For each drug, the optimal preparation has to be defined individually. 

The relative concentration of gadolinium can be significantly increased as compared to that achievable with liposomes because the physical stability of the mixed micelles is reached for relatively low amounts of additional lipids and surfactants. It is also worth mentioning that the gadolinium-heads of the complexes embedded in micelles are all exposed to the aqueous phase and can interact directly with the water molecules of the bulk, a situation which is usually not met with liposome systems. 

Aqueous dispersions of polymerizable lipids and surfactants can be polymerized by UV irradiation (Fig. 18). In the case of diacetylenic lipids the transition from monomeric to polymeric bilayers can be observed visually and spectroscopically. This was first discussed by Hub, 9) and Chapman 20). As in monomolecular layers (3.2.2) short irradiation brings about the blue conformation of the poly(diacetylene) chain. In contrast, upon prolonged irradiation or upon heating blue vesicles above the phase transition temperature of the monomeric hydrated lipid the red form of the polymer is formed 23,120). The visible spectra of the red form in monolayers and liposomes are qualitatively identical (Fig. 19). 

Recently, certain lipids and surfactants have been shown to reduce the activity of efflux transporters in the GI wall, and hence, to increase the fraction of drug absorbed. Because of the interplay between P-gp and CYP3A4 activity this mechanism may reduce intraen-terocyte metabolism as well. This issue will be further explained in detail separately (Section 6.3.2.2). 

Penetration enhancers have different mechanisms of action depending on their physicochemical properties. Some examples of penetration enhancers and their mechanisms are bile salts (micellization and solubilization of epithelial lipids), fatty acids such as oleic acid (perturbation of intracellular lipids) [25,26], azone (l-dodecylazacycloheptan-2-one) (increasing fluidity of intercellular lipids), and surfactants such as sodium lauryl sulfate (expansion of intracellular spaces). The complete list of enhancers and their mechanism of actions are discussed in detail in Chapter 10. 

The preferred method of delivery of oral microemulsion formulations is either as a combination of drug, lipid, and surfactant/cosurfactant (generally filled into soft or sealed hard gelatin capsules) that spontaneously microemulsify in the GIT, or as a microemulsion preconcentrate in which the dose form contains a small quantity of hydrophilic phase and is in itself a concentrated O/W or W/O microemulsion, which becomes diluted or phase inverted in the GI fluids. 

Fig. 1. Structural formulae of lipids and surfactants (a) — lecithin (b) — dihexadecylphosphate (c) — viologen...

Pietkiewicz J, Sznitowska M. The choice of lipids and surfactants for injectable extravenous microspheres. Pharmazie 2004 59 325-326. 

Figure 20.4. Molecular models of cutaway structures formed from the lipid-like peptides with negatively charged heads and glycine tails. Each peptide is c. 2 nm in length. (A, C) Peptide vesicle with an area sliced away. (B, D) Peptide tubes. The glycines are packed inside the bilayer away from water, and the aspartic acids are exposed to water, much like other lipids and surfactants. The modeled dimension is 50-100 nm in diameter. Preliminary experiments suggest that the wall thickness may be c. 4-5 nm, implying that the wall may form a double layer, similar to phospholipids in cell membranes.

These interactions are frequently ionic in character. The coulombic forces of interaction between macroions and lower molecular weight ionic species are central to the life processes of the cell. For example, intermolecular interactions of nucleic acids with proteins and small ions, of proteins with anionic lipids and surfactants and with the ionic substrates of enzyme catalyzed reactions, and of ionic polysaccharides with a variety of inorganic cations are all improtant natural processes. Intramolecular coulombic interactions are also important for determining the shape and stability of biopolymer structures, the biological function of which frequently depends intimately on the conformational features of the molecule. 

In comparison with the polymeric colloidal carriers mentioned so far, SLN are much more compatible with phagocytic cells. SLN composed of different lipids and surfactants do not exert any cytotoxic effects up to concentrations of 2.5% lipid, and even concentrations up to 10% led to a viability of 80% with human granulocytes [20]. Similar results were obtained in retinoic acid-differentiated HL-60 cells, whereas polymethylcyanoacrylate and polyhexylcyanoacrylate nanoparticles at concentrations of 0.05% or 0.35% led to complete cell death. In this chapter, the results of cytotoxicity testing of SLN on freshly isolated peritoneal mouse macrophages are presented. 

Photon Correlation Spectroscopy Diameters of Solid Lipid Nanoparticles Produced with Different Lipids and Surfactants (5% Lipid, 0.5% Surfactant) to Assess the Influence of the Matrix Lipid on the Biodegradation of the Corresponding Solid Lipid Nanoparticles... 

Lipid and Surfactant Diameter (nm) Standard Deviation (%) Polydispersity Index... 

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