Oil-in-Water Nanosized Emulsions for Drug Delivery and Targeting. Tamilvanan Shunmugaperumal. Читать онлайн. Newlib. NEWLIB.NET

Автор: Tamilvanan Shunmugaperumal
Издательство: John Wiley & Sons Limited
Серия:
Жанр произведения: Химия
Год издания: 0
isbn: 9781119585251
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surfactants used for emulsion stabilization contain small amounts of polar compounds that can be incorporated into the adsorption layer and lead to a modest droplet charge, which additionally stabilizes the emulsion (Tamilvanan 2008). Surface layer with charged natural admixtures reported by Trotta et al. (2002) is only a particular case of a very large class of emulsion‐stabilizing systems based on a tailored application of ionic–zwitterionic surfactant mixtures. Mixtures of dipalmitoylphosphatidylcholine (DPPC) and homologues and dimyristoylphosphatidylethanolamine (DMPE) phospholipids were utilized by Ishii and Nii (2005) for stabilizing model API‐carrying o/w nanosized emulsions. In contrast to the data, the main stability factor was found to be the optimal average hydrophilic–lipophilic balance (HLB) value of the stabilizers’ mixture, defined similarly for nonionic surfactants (Trotta et al. 2002). For example, emulsions prepared with mixtures of dimyristoylphosphatidylcholine (DMPC, zwitterionic) and DMPE behaved similarly to emulsions prepared by DMPC alone. This fact was explained by the equivalence of HLB values for both surfactants used, regardless of their ionic nature. However, the ionic character of a surfactant like DMPE (and therefore the charge of respective emulsion droplets) can be affected by the pH of the dispersion medium.

      Anionic emulsion formulations capture apolipoproteins (apo) along with other plasma proteins within minutes after an infusion in human blood, facilitating their fast elimination. In contrast, cationic emulsions reveal a much longer retention time in the plasma. Moreover, cationic colloidal carriers can promote the penetration of therapeutic agents into cell surfaces possibly via an endocytotic mechanism (Calvo et al. 1997). To improve the API targeting efficacy of colloidal carriers of anionic emulsions and to further prolong the circulating effect of the cationic emulsions, a mixed stabilizer film at the oil–water droplet interface composed of nonionic Poloxamer 188 and ionic lipoid E80 and stearylamine/oleylamine was created by combining the effects of electrostatic and steric barriers at the oil–water interface (Tamilvanan et al. 2005). In order to prove this concept, surface (charge)‐modified o/w nanosized emulsions (cationic and anionic) were prepared following the well‐established combined emulsification techniques (de novo) and these two emulsions were characterized for their droplet size distribution and surface charge. Marketed lipofundin MCT 10%, deoxycholic acid‐based anionic emulsions, oleylamine‐/stearylamine‐based cationic emulsions, and oleic acid‐based anionic emulsions were selected in this study. The effect of these emulsions on in vitro adsorption of plasma proteins was investigated by means of two‐dimensional polyacrylamide gel electrophoresis (2D PAGE).

Bar chart depicts the amount of major proteins on the 2-dimensional gels of plasma proteins adsorbed on emulsions with negative or positive surface charge in comparison with Lipofundin MCT 10-percent.

      [Taken with permission from Elsevier (Tamilvanan et al. 2005).]

      Most often used stabilizers for the preparation of emulsions, in the fields of agrochemicals, pharmaceuticals, and personal care products, are either block or graft copolymers. In block copolymers, the hydrophobic blocks reside at the surface or even partly penetrate in the oil droplet, making trains or short loops whereas the hydrophilic blocks protrude in the dispersion medium as loops or tails providing steric stabilization (Benichou et al. 2004). As examples, PEO‐PPO‐PEO triblock copolymer (commercially available as “Pluronics”) or PPO‐PEO‐PPO can be mentioned. Triblock copolymers are, however, not the most efficient stabilizers because the PPO chain is not hydrophobic enough to attach strongly at the o/w interface (Benichou et al. 2004). The surface activity of these polymeric surfactants is rather the result of a rejective anchoring or negative enthalpic energy change of the PPO group because of its low solubility in water and most oils. Alternative and more efficient graft copolymers consist of a polymeric backbone attached to the interface and several chains dangling into the continuous phase and forming at the interface a “brush” structure.

      A typical example of commercial graft was described (Jumaa and Müller 2002). Here, mixtures of polyoxyethylene‐660‐12‐hydroxystearate (Solutol HS15) with the anionic lipid composition. Lipoid S75 was employed to enhance the long term as well as accelerated (by freezing and centrifugation) stability of o/w nanosized emulsions. Emulsion stabilized by phospholipids displayed a stable behavior after autoclaving and centrifugation but de‐emulsified after freezing. In contrast, emulsions prepared only with Solutol HS15 demonstrated a significant change in particle size after autoclaving. The best results were obtained using a stabilizer mixture revealing a combination of electrostatic stabilization mechanism typical for the anionic phospholipids and the steric stabilization mechanism originating from nonionic