Abstract：
Liposomal formulations, as versatile nanocarrier systems suitable for targeted delivery, have a highly focused role in the therapy development of unmet clinical needs and diagnostic imaging techniques. Formulating nanomedicine with suitable zeta potential is an essential but challenging task. Formulations with a minimum ±30 mV zeta potential are considered stable. The charge of the phospholipid bilayer can be adjusted with membrane additives. The present Quality by Design-derived study aimed to optimise liposomal formulations prepared via the thin-film hydration technique by applying stearylamine (SA) or dicetyl phosphate (DCP) as charge imparting agents. This 32 fractional factorial design-based study determined phosphatidylcholine, cholesterol, and SA/DCP molar ratios for liposomes with characteristics meeting the formulation requirements. The polynomials describing the effects on the zeta potential were calculated. The optimal molar ratios of the lipids were given as 12.0:5.0:5.0 for the SA-PBS pH 5.6 (optimised sample containing stearylamine) and 8.5:4.5:6.5 for the DCP-PBS pH 5.6 (optimised sample containing dicetyl phosphate) particles hydrated with phosphate-buffered saline pH 5.6. The SA-PBS pH 5.6 liposomes had a vesicle size of 108 ± 15 nm, 0.20 ± 0.04 polydispersity index, and +30.1 ± 1.2 mV zeta potential, while these values were given as 88 ± 14 nm, 0.21 ± 0.02, and -36.7 ± 3.3 mV for the DCP-PBS pH 5.6 vesicles. The prepared liposomes acquired the requirements of the zeta potential for stable formulations.
摘要：
脂质体制剂，作为适用于靶向递送的多功能纳米载体系统，在未满足的临床需求和诊断成像技术的治疗发展中具有高度集中的作用。配制具有合适ζ电位的纳米药物是一项必不可少但具有挑战性的任务。具有最小±30mVζ电位的制剂被认为是稳定的。磷脂双层的电荷可以用膜添加剂调节。当前基于设计的质量研究旨在通过使用硬脂胺（SA）或磷酸二乙酯（DCP）作为电荷赋予剂，优化通过薄膜水合技术制备的脂质体制剂。这项基于32分数阶乘设计的研究确定了磷脂酰胆碱，胆固醇,和特征满足制剂要求的脂质体的SA/DCP摩尔比。计算了描述对ζ电位影响的多项式。对于SA-PBSpH5.6(含有硬脂胺的优化样品),脂质的最佳摩尔比给出为12.0:5.0:5.0,对于用磷酸盐缓冲盐水pH5.6水合的DCP-PBS(含有磷酸二乙酯的优化样品),脂质的最佳摩尔比给出为8.5:4.5:6.5。SA-PBSpH5.6脂质体的囊泡尺寸为108±15nm，0.20±0.04多分散指数，和+30.1±1.2mVzeta电位，虽然这些值为88±14nm，对于pH为5.6的DCP-PBS囊泡，为0.21±0.02和-36.7±3.3mV。制备的脂质体获得了稳定制剂的ζ电位的要求。
