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 (C_18:1EO₂₀, 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. k_BT, before vesicle transformation into non-vesicular aggregates began. For a soybean phosphatidylcholine concentration of 5.0 mmol kg⁻¹, the bilayer bending rigidity reached 1.5 k_BT at the total deoxycholate concentration of 4.1 mmol kg⁻¹ and 3.4 k_BT at the total polysorbate 80 concentration of 2.0 mmol kg⁻¹. In the case of C_18:1EO₂₀, the bilayer bending rigidity reached 1.5 k_BT 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.

可变形性不仅仅是一个非常有趣的囊泡特征；它也是一个重要的特征。它也是囊泡穿过皮肤屏障能力的关键决定因素；即皮肤渗透性。因此，用于跨皮肤递送药物和疫苗的双层囊泡的开发应涉及优化该特性，该特性可通过囊泡双层内或附近的双层软化剂的浓度来控制。为此，我们提出了一种简单的方法来量化双层软化剂对双层囊泡变形性的影响。该方法从囊泡尺寸对软化剂浓度的依赖性得出囊泡双层的弯曲刚度。为了举例说明该方法，我们研究了大豆磷脂酰胆碱与阴离子脱氧胆酸钠、非离子聚氧乙烯 (20) 脱水山梨醇油酯（聚山梨酯 80）或非离子聚氧乙烯 (20) 油基醚（C _18:1 EO ₂₀ ，Brij）的混合物^®98 ）。对于每一种测试的双层软化剂，所得混合两亲性囊泡双层的弯曲刚度随着双层软化剂浓度的增加呈准指数下降，正如人们在理论基础上所预期的那样。在囊泡开始转变为非囊泡聚集体之前，双层弯曲刚度达到较低值，接近热稳定性极限，即k _B T 。对于大豆磷脂酰胆碱浓度为5.0 mmol kg ^-1的情况，双层弯曲刚度在总脱氧胆酸盐浓度为4.1 mmol kg ^-1时达到1.5 k _B T ，在总聚山梨酯80浓度为2.0 mmol kg ^-1时双层弯曲刚度达到3.4 k _B T 。 在C _18:1 EO ₂₀的情况下，双层表面占有率α =0.1时双层弯曲刚度达到1.5k _B T 。因此，囊泡大小对双层软化剂浓度的依赖性揭示了囊泡转变为不同的聚集结构（例如皮肤渗透性差的混合胶束）以及关于囊泡变形性的实用有价值的信息。我们的结果与文献测量的结果相比毫不逊色。我们提供使用新分析方法优化可变形囊泡配方的实用指导。