Lipid colloidal systems

Table 18.6 Physical Characteristics of Different Lipid Colloidal Systems ...

The procedure chosen for the preparation of lipid complexes of AmB was nanoprecipitation. This procedure has been developed in our laboratory for a number of years and can be applied to the formulation of a number of different colloidal systems liposomes, microemulsions, polymeric nanoparticles (nanospheres and nanocapsules), complexes, and pure drug particles (14-16). Briefly, the substances of interest are dissolved in a solvent A and this solution is poured into a nonsolvent B of the substance that is miscible with the solvent A. As the solvent diffuses, the dissolved material is stranded as small particles, typically 100 to 400 nm in diameter. The solvent is usually an alcohol, acetone, or tetrahydrofuran and the nonsolvent A is usually water or aqueous buffer, with or without a hydrophilic surfactant to improve colloid stability after formation. Solvent A can be removed by evaporation under vacuum, which can also be used to concentrate the suspension. The concentration of the substance of interest in the organic solvent and the proportions of the two solvents are the main parameters influencing the final size of the particles. For liposomes, this method is similar to the ethanol injection technique proposed by Batzii and Korn in 1973 (17), which is however limited to 40 mM of lipids in ethanol and 10% of ethanol in final aqueous suspension. 

In Part Four (Chapter eight) we focus on the interactions of mixed systems of surface-active biopolymers (proteins and polysaccharides) and surface-active lipids (surfactants/emulsifiers) at oil-water and air-water interfaces. We describe how these interactions affect mechanisms controlling the behaviour of colloidal systems containing mixed ingredients. We show how the properties of biopolymer-based adsorption layers are affected by an interplay of phenomena which include selfassociation, complexation, phase separation, and competitive displacement. 

For example, the use of a conically shaped lipid, dioleoylphos-phatidylethanolamine (DOPE), in cationic liposomes helps the destabilization of the cellular membranes, leading to a more efficient delivery of plasmid DNA in cell culture.84 The structural diversity of the lipidic colloids offers great flexibility in their applications as drug delivery and drug targeting systems. 

Emulsions and suspensions are colloidal dispersions of two or more immiscible phases in which one phase (disperse or internal phase) is dispersed as droplets or particles into another phase (continuous or dispersant phase). Therefore, various types of colloidal systems can be obtained. For example, oil/water and water /oil single emulsions can be prepared, as well as so-called multiple emulsions, which involve the preliminary emulsification of two phases (e.g., w/o or o/w), followed by secondary emulsification into a third phase leading to a three-phase mixture, such as w/o/w or o/w/o. Suspensions where a solid phase is dispersed into a liquid phase can also be obtained. In this case, solid particles can be (i) microspheres, for example, spherical particles composed of various natural and synthetic materials with diameters in the micrometer range solid lipid microspheres, albumin microspheres, polymer microspheres and (ii) capsules, for example, small, coated particles loaded with a solid, a liquid, a solid-liquid dispersion or solid-gas dispersion. Aerosols, where the internal phase is constituted by a solid or a liquid phase dispersed in air as a continuous phase, represent another type of colloidal system. 

The stability of colloidal systems consisting of charged particles can be essentially explained by the Derjaguin-Landau-Verwey-Overbeek (DLVO) theory [1-7]. According to this theory, the stability of a suspension of colloidal particles is determined by the balance between the electrostatic interaction and the van der Waals interaction between particles. A number of studies on colloid stability are based on the DLVO theory. In this chapter, as an example, we consider the interaction between lipid bilayers, which serves as a model for cell-cell interactions [8, 9]. Then, we consider some aspects of the interaction between two soft spheres, by taking into account both the electrostatic and van der Waals interactions acting between them. 

Various colloidal systems have been studied for use as potential ophthalmic delivery systems, including liposomes and nanoparticles. Liposomes are bioerodible and biocompatible systems consisting of microscopic vesicles composed of lipid bilayers surrounding aqueous compartments. Liposomes have demonstrated prolonged drug effect at the site of action but with reduced toxicity. Ophthalmic studies have included topical, subconjunctival, and intravitreal administration, but no commercial preparations are currently available for ophthalmic use. 

Lipids exist in most foods as multiphased colloidal systems bound by surface-active phospholipids, proteins and emulsifiers. The oxidative stability of food lipids is greatly affected by the partitioning of the lipid substrates, metal initiators and antioxidants, which is complex and depends on the physical properties of the food. We may consider three types of food systems (see Chapter 10) ... 

The term interfacial oxidation refers to the complex interaction between constituents in multiphase lipid systems in either promoting or inhibiting lipid oxidation. Interfacial oxidation is a surface reaction dependent on the rate of oxygen diffusion and its interactions with unsaturated lipids, metal initiators, radical generators and terminators, all of which are distributed in different compartments of colloidal systems. 

The term "lipid nanoparticles" includes all colloidal systems where the nanoparticles consist of a kind of lipid matrix whereas the matrix lipid can occur in different physicochemical states (Figure 9.1) isotropic liquid (e.g. conventional fat emulsions), liquid crystalline (e.g. lyotropic cubic and thermotropic smectic ) or solid crystalline (SLN). A further distinction can be made if the lipid matrix is continuous (emulsions, SLN) or presents a discontinuous network of e.g. lipid bilayers (e.g. cubic nanoparticles). However, it should be kept in mind that lipid nanoparticles in several physicochemical states may coexist in one formulation. Generally the mean size of the nanoparticles is in the mid to lower nm-range normally between 100 and 500 nm. 

In absorption studies, the appUcation of colloidal systems, which show specific and unspecific interactions with mainly lipophilic substances is of main interest. An obvious application is the study of lipophilic and poorly absorbable drugs that are administered orally or transdermally. Such interactions with surface-active agents may either cause a diminution of the bioavailability by trapping the drug in the micelle or, on the other hand, lead to an improved solubility (prevention of the precipitation of the drug) and facilitated transfer of the solute across lipid membranes (e.g., the intestinal wall in the gastrointestinal tract) and therefore to an improved bioavailability. 

As mentioned above, food systems are complex multiphase products that may contain dispersed components such as sohd particles, hquid droplets or gas bubbles. The continuous phase may also contain colloidally dispersed macromolecules such as polysaccharides, protein and lipids. These systems are non-Newtonian, showing complex rheology, usually plastic or pseudo-plastic (shear thinning). Complex structural units are produced as a result of the interaction between the particles of the disperse phase as well as by interaction with polymers that are added to control the properties of the system, such as its creaming or sedimentation as well as the flow characteristics. The control of rheology is important not only during processing but also for control of texture and sensory perception. 

It is hoped to have shown that micropipet manipulation is an incredibly versatile technique. It enables the study of a wide range of giant vesicle behavior and properties, including the material properties of bilayers, their colloidal interactions, and the uptake and desorption of a variety of macromolecules. These direct measurements on single giant vesicles then help to characterize the properties of natural cell membranes and also provide the essential information needed for the design and ultimate application of lipid vesicle and lipid-coated systems in biotechnology and medicine. 

In special cases (as in colloidal solutions) some particles can be considered as essential and other particles as irrelevant , but in most cases the essential space will itself consist of collective degrees of freedom. A reaction coordinate for a chemical reaction is an example where not a particle, but some function of the distance between atoms is considered. In a simulation of the permeability of a lipid bilayer membrane for water [132] the reaction coordinate was taken as the distance, in the direction perpendicular to the bilayer, between the center of mass of a water molecule and the center of mass of the rest of the system. In proteins (see below) a few collective degrees of freedom involving all atoms of the molecule, describe almost all the... 

---