and consequently, due to a lower electrostatic repulsion between the colloidal droplets (Goldstein et al. 2007b). On the other hand, immunoemulsions stabilized by both anionic and cationic emulsifiers exhibited a multifold increase in cell binding in contrast to the emulsions without antibodies.
The cationic o/w nanosized emulsions were also found to be effective vehicles to improve the skin permeability of incorporated lipophilic molecules in dermatological applications (Yilmaz and Borchert 2005). Because epithelial cells of the skin carry a negative surface charge, they show high selectivity and permeability to positively charged solutes. Thus, positively charged nanosized emulsions are promising systems for enhancing the skin permeability for APIs included in the colloidal droplets. The authors also showed that ceramides could be successfully delivered in a transdermal route by means of nanosized emulsions stabilized by a positively charged interfacial layer of the naturally occurring molecule, phytosphingosine. Other applications of nanosized emulsions as carriers, stabilized by ionic surfactants, in the pharmaceutical and cosmetic fields have been briefly reviewed by Solans et al. (2005) and Tamilvanan (2008).
Anionic phospholipids are also commonly utilized for the stabilization of API‐carrying nanosized emulsion droplets both individually and in binary mixtures (Trotta et al. 2002). Soybean lecithin and modified phospholipid, n‐hexanoyl lysolecithin (6‐PC), alone and as 1 : 1 mixtures were used as stabilizers of MCT droplets in water (Trotta et al. 2002). Although individual uncharged phospholipids provide emulsion droplets, a moderate negative charge for stabilization, mixed phospholipids produce much more stable emulsions and a large negative zeta‐potential value. A possible explanation for this phenomenon is related to the increased incorporation of polar compounds from the soya lecithin into the mixed interfacial film when 6‐PC is present. This interfacial film acts as a stabilizer by forming a high energy barrier that repels adjacent droplets and leads to the formation of stabilized emulsified droplets. The stability of the emulsion did not noticeably change, even in the presence of the model destabilizing API, indomethacin, demonstrating the high potential for such mixed emulsifiers for the formulation of colloidal API delivery systems (Trotta et al. 2002). Lysolecithin has one fatty acid ester chain removed from the glycerol backbone, in addition, lysolecithin is toxic (destroys RBC cell membranes). Furthermore, although the role of phospholipids is essential for the stability of the emulsions, possible cataractogenic effects due to the phosphatidyl choline (PC) and, basically, to a derivative of the same, lysophosphatidyl, have been described by different authors (Cotlier et al. 1975; Kador and Kinoshita 1978).
A new class of surface‐active dialkyl maleates can be utilized for emulsion polymerization (Abele et al. 1997). Here, the emulsion droplets of monomeric maleates are self‐stabilized and simultaneously serve as liquid “reactive storage carriers.” Three types of head group in the dialkyl maleates were studied—nonionic, cationic, and zwitterionic with different lengths of hydrophobic alkyl chain. Cationic and zwitterionic dialkyl maleates with the longest alkyl chains ‐C16H33 and ‐C17H35 provided the best stability for o/w nanosized emulsions. When compared with the data obtained for the well‐known nonionic surfactant nonylphenol‐poly (ethylene oxide) (NPEO10) and the cationic cetyltrimethyl ammonium bromide (CTAB), an excellent stabilizing capacity especially for the cationic maleates can be stated. Whereas nonionic dialkyl maleates show almost the same emulsifying ability and stability as NPEO10, the cationic derivatives of these novel surfactants are more effective in stabilization than the traditional CTAB.
Sometimes anionic surfactants are especially added to emulsion droplets for the stabilization of “reactive storage carriers” subjected to further chemical transformation. Sodium dodecyl sulfate (SDS) was utilized to stabilize miniemulsion droplets, which in the subsequent step, were polymerized and formed poly(n‐butylcyanoacrylate) (PBCA) nanoparticles, suitable for targeting API delivery to specific cells (Weiss et al. 2007). It is worth mentioning that SDS is predominantly used to achieve required miniemulsion stability (Landfester 2006). In some cases, however, cationic surfactants are also used in miniemulsion formulations, which were reported first in the late seventies of the 20th century. In general, however, stability of miniemulsions does not depend on the sign of the surfactant charge and is mainly determined by the surfactant coverage of the reactive carriers (miniemulsion droplets). The same factor is also crucial for the size of miniemulsion droplets after steady‐state miniemulsions are obtained (Landfester 2006).
2.2.4. Importance of Neutral‐Charged (Sterically Stabilized) Nanosized Emulsions
In many cases, however, greater emulsion stability can be achieved without imparting a significant surface charge to the emulsion droplets, by means of steric stabilization (Capek 2004). Nonionic surfactants possessing bulky hydrophilic groups like PEO protruding into the dispersion media decrease coalescence arising from droplet collisions. Another contribution to the steric stabilization of emulsions by nonionic surfactants is provided by the close packing of PEO chains at the droplet surface. The compact packing of PEO chains at the droplet surface creates steric stabilization because little or no interpenetration of PEO chains on different droplet surfaces occurs due to entropic repulsion (Dale et al. 2006). Large head groups carrying simultaneously charges of opposite signs, such as in zwitterionic surfactants, can cause similar effects. In polar dispersion media of low‐to‐medium ionic strength, these groups are, as a rule, strongly solvated (hydrated in the most common case of H2O) (Yaseen et al. 2006). Voluminous and on an average almost non‐charged hydration shells, surrounding the emulsion droplet, possess a significant steric rigidity and can also effectively stabilize emulsions. There are, however, only a few examples in the literature that use zwitterionic surfactants as effective emulsion stabilizers. For example, lecithin was used for the stabilization of perfluorooctyl bromide (PFOB) in water emulsions, to be used as oxygen‐carrying system in a bio‐artificial liver device (Moolman et al. 2004). The Sauter mean diameter of 0.2 μm PFOB emulsion droplet in water was obtained by high‐pressure homogenization. The emulsion was stable for several months even at a volume fraction of 20%. Nonionic surfactants are more often used for emulsion stabilization than zwitterionic phospholipids because they are synthetically manufactured, can be well defined analytically, and have significantly less batch‐to‐batch variation than naturally occurring (egg yolk, soybean) lecithins.
The nonionic surfactant Span‐83 was used for stabilizing water droplets in oil to form a reactive storage carrier for the synthesis of calcium carbonate nanoparticles by means of a two membrane system (Hu et al. 2004). Firstly, an aqueous emulsion was prepared in kerosene stabilized by 0.02596 wt% Span and containing CO3−2 ions in the droplets of the dispersed phase. The oil phase contained also a 0.02792 M solution of bis(2‐ethylhexyl) hydrogen phosphate (2DEHPA), a well‐known molecular carrier for the transportation of metal ions across emulsion liquid membranes (ELM). In the second stage, a CaCl2 aqueous solution‐filled dialysis tube was placed into the o/w emulsion and due to the reaction between CO3−2 and Ca2+ ions in the aqueous droplets, CaCO3 nanoparticles were obtained. Similarly, ZnS nanoparticles were prepared in inverse water‐oil‐emulsion (Naskar et al. 2006). The stabilization of emulsions was provided by the addition of 5 wt% of Span 80 or Span 20, respectively, to the oil phase (cyclohexane). The dispersed phase contained a mixture of zinc acetate and thioacetamide, which react upon heating to form ZnS. The authors demonstrated that for the preparation of ZnS nanoparticles, the use of Span 20 was more favorable because of the smaller emulsion droplet size and therefore lower and more homogeneous size of the final particles. Another advantage was the higher stability of Span 20 against hydrolysis as compared to Span 80.
In general, fulfilling both stabilization mechanisms (smaller droplet size and lesser susceptibility of surfactant toward chemical degradation) simultaneously leads not only to the highest emulsion stability but also to lesser sensitivity to changes in the external conditions such as pH, ionic strength, and temperature. Therefore, the use of mixtures of different classes of surfactants for emulsion stabilization is frequently the most effective solution in many practical cases.
2.2.5. Advantages of Nanosized Emulsions Stabilized by Mixed or Multicomponent Emulsifier Molecules