Wachter Christian, Vierl Ulrich, Cevc Gregor
IDEA AG, Frankfurter Ring 193a, Munich, Germany.
J Drug Target. 2008 Aug;16(7):611-25. doi: 10.1080/10611860802230158.
Novel potential carriers for non-invasive drug delivery were prepared from polyoxyethylene(20) oleyl ether (C(18:1)EO(20)) and soybean phosphatidylcholine (SPC) in different relative molar ratios, R(e); this produced stiff SPC liposomes (2r(ves) approximately 120 nm) at one end and much smaller (2r(mic) <or= 15 nm), comparably non-deformable, mixed micelles at the other end of aggregate spectrum. Deformability of the mixed amphiphat vesicles (2r(v) approximately 105 nm) existing in-between increases with R(e) non-linearly, up to a quasi-plateau at R(e) >or= R(e)(sat) = 0.25 in the bilayer. The surfactant-saturated bilayers exhibit bending rigidity of kappa(c) approximately 2.1 k(B)T, as determined with an improved vesicle adaptability assay involving analysis of normalised flux density through a nano-porous barrier as an activated transport process. Pore penetrability vs. driving pressure data measured with the mixed amphiphat vesicles resemble results of computer simulation of deformable vesicles penetrating a constriction [Gompper G, Kroll DM. 1995. Driven transport of fluid vesicles through narrow pores. Phys Rev E Stat Phys Plasmas Fluids Relat Interdiscip Topics. 52:4198-4208], confirming basic similarity of both processes. The improved assay can reveal partial lipid solubilisation at R(e)>R(e)(sat), which is linearly proportional to R(e) - R(e)(sat). C(18:1)EO(20)-SPC mixed vesicles that can cross narrow pores are arguably suitable for targeted drug delivery across intact skin.
以不同相对摩尔比R(e),由聚氧乙烯(20)油醚(C(18:1)EO(20))和大豆磷脂酰胆碱(SPC)制备了用于非侵入性药物递送的新型潜在载体;这在聚集谱的一端产生了刚性的SPC脂质体(2r(ves)约为120 nm),而在另一端产生了小得多(2r(mic)≤15 nm)、相对不可变形的混合胶束。存在于两者之间的混合两亲性囊泡(2r(v)约为105 nm)的可变形性随R(e)呈非线性增加,在双层中R(e)≥R(e)(sat)=0.25时达到准平稳状态。通过一种改进的囊泡适应性测定法确定,表面活性剂饱和双层的弯曲刚度κ(c)约为2.1 k(B)T,该测定法涉及将通过纳米多孔屏障的归一化通量密度作为活化传输过程进行分析。用混合两亲性囊泡测量的孔渗透性与驱动压力数据类似于可变形囊泡穿透狭窄通道的计算机模拟结果[Gompper G, Kroll DM. 1995. Driven transport of fluid vesicles through narrow pores. Phys Rev E Stat Phys Plasmas Fluids Relat Interdiscip Topics. 52:4198 - 4208],证实了这两个过程的基本相似性。改进后的测定法可以揭示在R(e)>R(e)(sat)时的部分脂质溶解,其与R(e)-R(e)(sat)成线性比例。可以穿过狭窄通道的C(18:1)EO(20)-SPC混合囊泡可以说是适用于完整皮肤的靶向药物递送。