Libster Dima, Aserin Abraham, Yariv Doron, Shoham Gil, Garti Nissim
Casali Institute of Applied Chemistry, The Institute of Chemistry, The Hebrew University of Jerusalem, Jerusalem 91904, Israel.
Colloids Surf B Biointerfaces. 2009 Nov 1;74(1):202-15. doi: 10.1016/j.colsurfb.2009.07.020. Epub 2009 Jul 23.
This paper describes the formation and characterization of liquid crystalline dispersions based on the hexagonal phase of GMO/tricaprylin/water. As a stabilizer of the soft particles dispersed in the aqueous phase, a non-ionic, non-polymeric surfactant--ethoxylated phytosterol with 30 oxyethylene units (PhEO) was utilized. In contrast to Pluronic copolymers, normally utilized in the stabilization of liquid crystalline dispersions with ordered inner structure, use of such non-polymeric surfactant is not a common practice in this field. We revealed how properties of these particles, such as internal structure, size, and stability, can be rationally modified by the concentration of the stabilizing agent and processing conditions. The physical stability of the hexosomes was further examined by the LUMiFuge technique. Structural effect of PhEO solubilization on the properties of the bulk H(II) mesophase system showed that phase behavior was greatly influenced following phase transitions: H(II)-->H(II)+cubic-->cubic+L(alpha)-->L(alpha). The decrease of hydrogen bonding of the hydroxyl and carbonyl groups of monoolein with water and simultaneous hydration of EO groups of PhEO appeared to be important for the observed behavior. The use of PhEO as a dispersant resulted in a soft matter multi-phase water dispersion with bimodal distribution of the particle population. Effective stabilization of hexosomes was obtained in an extremely narrow concentration range of PhEO (0.1-0.2 wt%), coexisting with small vesicles and disordered particles. At higher PhEO content, particles had disordered inner structure, and unilamellar and multilamellar vesicles, at the expense of hexosomes in consequence of incorporation of the dispersant into the hexosome structure. PhEO was found to induce lamellar phase formation, introducing disorder into the hexagonal LLC and reducing their domain size. Finally, hexosomes were evaluated as delivery vehicles for the therapeutic peptide desmopressin. Sustained release of this drug was observed during the first 10 h; however, permeation drastically increased in the 10-24 h range.
本文描述了基于甘油单油酸酯/三辛酸甘油酯/水六方相的液晶分散体的形成与表征。作为分散于水相中的软颗粒的稳定剂,使用了一种非离子、非聚合表面活性剂——具有30个氧化乙烯单元的乙氧基化植物甾醇(PhEO)。与通常用于稳定具有有序内部结构的液晶分散体的普朗尼克共聚物不同,使用这种非聚合表面活性剂在该领域并不常见。我们揭示了如何通过稳定剂浓度和加工条件合理改变这些颗粒的性质,如内部结构、尺寸和稳定性。通过LUMiFuge技术进一步研究了六边体的物理稳定性。PhEO增溶对本体H(II)中间相体系性质的结构效应表明,相变后相行为受到很大影响:H(II)-->H(II)+立方相-->立方相+L(α)-->L(α)。单油酸甘油酯的羟基和羰基与水的氢键减少以及PhEO的EO基团同时水合似乎对观察到的行为很重要。使用PhEO作为分散剂导致形成了具有双峰颗粒分布的软物质多相水分散体。在极窄的PhEO浓度范围(0.1 - 0.2 wt%)内实现了六边体的有效稳定,同时存在小囊泡和无序颗粒。在较高的PhEO含量下,颗粒具有无序的内部结构以及单层和多层囊泡,这是由于分散剂掺入六边体结构导致六边体减少。发现PhEO会诱导层状相形成,使六方液晶复合物产生无序并减小其域尺寸。最后,评估了六边体作为治疗性肽去氨加压素的递送载体。在最初的10小时内观察到该药物的持续释放;然而,在10 - 24小时范围内渗透急剧增加。