a Department of Human Health Therapeutics , National Research Council Canada , Ottawa , Canada.
b Department of Measurement Science and Standards , National Research Council Canada , Ottawa , Canada.
J Liposome Res. 2018 Dec;28(4):305-314. doi: 10.1080/08982104.2017.1376683. Epub 2017 Sep 26.
Archaeosomes composed of archaeal total polar lipids (TPL) or semi-synthetic analog vesicles have been used as vaccine adjuvants and delivery systems in animal models for many years. Typically administered by intramuscular or subcutaneous injections, archaeosomes can induce robust, long-lasting humoral and cell-mediated immune responses against entrapped antigens and provide protection in murine models of infectious disease and cancer. Herein, we evaluated various archaeosomes for transdermal delivery, since this route may help eliminate needle-stick injuries and needle re-use, and therefore increase patient compliance. Archaeosomes composed of TPL from different archaea (Halobacterium salinarum, Methanobrevibacter smithii, Haloferax volcanii) and various semi-synthetic glycolipid combinations were evaluated for their ability to diffuse across the skin barrier using an ex vivo pig skin model and the results were compared to conventional synthetic ester liposomes. Physicochemical characteristics were determined for selected formulations including vesicle size, size distribution, zeta potential, fluidity, antigen (ovalbumin) incorporation efficiency and release. Archaeosomes, in particular those composed of M. smithii TPL or the synthetic glycolipid sulfated S-lactosylarchaeol (SLA) mixed with uncharged glycolipid lactosyl archaeol (LA), appeared to be effective carriers for ovalbumin, achieving much better antigen distribution and vesicle accumulation in the skin epidermis than conventional liposomes. The enhanced skin permeation of archaeosomes may be attributed to their chemical structure and physicochemical properties such as particle size, surface charge, stability, and fluidity of their lipid bilayer.
多年来，由古菌总极性脂（TPL）或半合成类似囊泡组成的 archaeosomes 已被用作动物模型中的疫苗佐剂和递药系统。通常通过肌内或皮下注射给药， archaeosomes 可以诱导针对包封抗原的强大、持久的体液和细胞介导的免疫应答，并为感染性疾病和癌症的小鼠模型提供保护。在此，我们评估了各种 archaeosomes 用于经皮给药，因为这种途径可能有助于消除针刺损伤和针重复使用，从而提高患者的依从性。使用离体猪皮模型评估了来自不同古菌（盐沼盐杆菌、甲烷短杆菌、沃氏嗜盐菌）的 TPL 组成的 archaeosomes 以及各种半合成糖脂组合的能力，以确定它们穿过皮肤屏障的扩散能力，并将结果与传统的合成酯质体进行比较。对选定的制剂进行了物理化学特性的测定，包括囊泡大小、粒径分布、zeta 电位、流动性、抗原（卵清白蛋白）包封效率和释放。 archaeosomes，特别是由 M. smithii TPL 或合成糖脂硫酸化 S-乳糖基古醇（SLA）与不带电荷的糖脂乳糖基古醇（LA）混合组成的 archaeosomes，似乎是卵清白蛋白的有效载体，与传统脂质体相比，在皮肤表皮中实现了更好的抗原分布和囊泡积累。 archaeosomes 的增强的皮肤渗透可能归因于其化学结构和物理化学特性，例如粒径、表面电荷、稳定性和脂质双层的流动性。
