Department of Pharmaceutics, College of Pharmacy, University of Hail, Hail, Saudi Arabia; Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt.
Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt.
Chem Phys Lipids. 2018 Jan;210:98-108. doi: 10.1016/j.chemphyslip.2017.10.008. Epub 2017 Oct 28.
Deformability is not just a fundamentally interesting vesicle characteristic; it is also the key determinant of vesicle ability to cross the skin barrier; i.e. skin penetrability. Development of bilayer vesicles for drug and vaccine delivery across the skin should hence involve optimization of this property, which is controllable by the concentration of bilayer softeners in or near the vesicle bilayers. To this end, we propose a simple method for quantifying the effect of bilayer softeners on deformability of bilayer vesicles. The method derives the bending rigidity of vesicle bilayers from vesicle size dependence on softener concentration. To exemplify the method, we studied mixtures of soybean phosphatidylcholine with anionic sodium deoxycholate, non-ionic polyoxyethylene (20) sorbitan oleyl ester (polysorbate 80), or non-ionic polyoxyethylene (20) oleyl ether (CEO, Brij 98). With each of the tested bilayer softeners, the bending rigidity of the resulting mixed-amphipat vesicle bilayers decreased quasi-exponentially as the concentration of the bilayer softener increased, as one would expect on theoretical ground. The bilayer bending rigidity reached low values, near the thermal stability limit, i.e. kT, before vesicle transformation into non-vesicular aggregates began. For a soybean phosphatidylcholine concentration of 5.0mmolkg, the bilayer bending rigidity reached 1.5kT at the total deoxycholate concentration of 4.1mmolkg and 3.4kT at the total polysorbate 80 concentration of 2.0mmolkg. In the case of CEO, the bilayer bending rigidity reached 1.5kT at the bilayer surface occupancy α=0.1. The dependence of vesicle size on bilayer softener concentration thus reveals vesicle transformation into different aggregate structures (such as mixed micelles with poor skin penetrability) and practically valuable information on vesicle deformability. Our results compare favorably with results of literature measurements. We provide practical guidance on using the new analytical method to optimize deformable vesicle formulations.
变形性不仅是囊泡的一个基本特性，也是囊泡穿越皮肤屏障的关键决定因素，即皮肤渗透性。因此，为了通过皮肤递药和递疫苗，双层囊泡的开发应涉及对这一特性的优化，而这一特性可通过双层柔软剂在囊泡双层内外的浓度来控制。为此，我们提出了一种定量评估双层柔软剂对双层囊泡变形性影响的简单方法。该方法从囊泡大小对柔软剂浓度的依赖性中推导出囊泡双层的弯曲刚度。为了举例说明该方法，我们研究了大豆卵磷脂与阴离子去氧胆酸钠、非离子聚氧乙烯（20）失水山梨醇油酸酯（聚山梨酯 80）或非离子聚氧乙烯（20）油醚（Brij 98）的混合物。对于每种测试的双层柔软剂，随着双层柔软剂浓度的增加，所得混合两性囊泡双层的弯曲刚度呈近指数下降，这与理论预期一致。双层弯曲刚度在接近热稳定性极限（即 kT）之前达到低值，此时囊泡开始转化为非囊泡聚集物。对于 5.0mmolkg 的大豆卵磷脂浓度，在总去氧胆酸钠浓度为 4.1mmolkg 时双层弯曲刚度达到 1.5kT，在总聚山梨酯 80 浓度为 2.0mmolkg 时达到 3.4kT。在 Brij 98 的情况下，当双层表面占有率α=0.1 时，双层弯曲刚度达到 1.5kT。囊泡大小随双层柔软剂浓度的变化揭示了囊泡转化为不同的聚集结构（如具有较差皮肤渗透性的混合胶束）的情况，以及囊泡变形性的实际有价值的信息。我们的结果与文献测量结果相当。我们为使用新的分析方法优化可变形囊泡配方提供了实用指导。
