Laboratorio de Biomembranas, Departamento de Ciencia y Tecnología, Universidad Nacional de Quilmes, Bernal, Buenos Aires, Argentina.
J Liposome Res. 2011 Jun;21(2):124-33. doi: 10.3109/08982104.2010.491073. Epub 2010 Jun 16.
Vaccine development today encounters a main obstacle, which is the need for effective adjuvants suitable for clinical trials. Aluminum salts, discovered 70 years ago and, very recently, MF59, are the only types of adjuvants currently used in vaccines licensed by the U.S. Food and Drug Administration. Liposomes represent an alternative approach to vaccine adjuvants. In this article, we describe the inflammatory response and biological effect of polymerization and the addition of positive charges in liposome formulations. Nonpolymerized cationic (NP(+)) liposomes significantly reduce metabolism in Vero cells after 24 hours. Correspondingly, both NP(+) and polymerized cationic (P(+)) liposomes reduce cell viability following a 48-hour incubation. Similar results were obtained with cells from the peritoneal cavities of mice. Paradoxically, those liposomes that presented clearly cytostatic or cytotoxic effects in vitro stimulated metabolism and had a mitogenic effect in vivo. Finally, the adjuvant effect was tested by immunization in BALB/c mice. The major effect was obtained with NP(+) liposomes. Accordingly, we also demonstrated that NP(+) liposomes injected into the dermis produced an outstanding inflammatory reaction, showing the histopathological characteristics of an inoculation granuloma. Thus, positive charge would play an important role in the immunoadjuvant effect of liposomes by conferring them cytotoxic capacity.
疫苗开发目前面临一个主要障碍,即需要适用于临床试验的有效佐剂。铝盐在 70 年前被发现,而最近的 MF59 是目前美国食品和药物管理局批准的疫苗中使用的唯一佐剂类型。脂质体是疫苗佐剂的另一种方法。在本文中,我们描述了聚合和脂质体制剂中带正电荷的添加物的炎症反应和生物学效应。未聚合的阳离子(NP(+))脂质体在 24 小时后显著降低了 Vero 细胞的代谢。相应地,NP(+)和聚合阳离子(P(+))脂质体在孵育 48 小时后均降低了细胞活力。用来自小鼠腹腔的细胞也得到了类似的结果。矛盾的是,那些在体外表现出明显的细胞抑制或细胞毒性作用的脂质体刺激了代谢,并在体内具有有丝分裂作用。最后,通过 BALB/c 小鼠免疫接种测试了佐剂作用。主要作用是由 NP(+)脂质体产生的。因此,我们还证明了注入真皮的 NP(+)脂质体产生了出色的炎症反应,显示出接种性肉芽肿的组织病理学特征。因此,正电荷通过赋予脂质体细胞毒性能力,在脂质体的免疫佐剂作用中发挥重要作用。
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