Relationship between the adjuvant and cytotoxic effects

JULIETA GASPARRI; LUCÍA SPERONI; NADIA CHIARAMONI; SILVIA ALONSO

JOURNAL OF LIPOSOME RESEARCH

TAYLOR & FRANCIS INC

Lugar: Londres; Año: 2010

0898-2104

Vaccine development today encounters a main obstacle, which is the need for effective adjuvants suitablefor clinical trials. Aluminum salts, discovered 70 years ago and, very recently, MF59, are the only types of adjuvantscurrently used in vaccines licensed by the U.S. Food and Drug Administration. Liposomes represent analternative approach to vaccine adjuvants. In this article, we describe the inflammatory response and biologicaleffect of polymerization and the addition of positive charges in liposome formulations. Nonpolymerizedcationic (NP+) liposomes significantly reduce metabolism in Vero cells after 24 hours. Correspondingly, bothNP+ and polymerized cationic (P+) liposomes reduce cell viability following a 48-hour incubation. Similarresults were obtained with cells from the peritoneal cavities of mice. Paradoxically, those liposomes thatpresented clearly cytostatic or cytotoxic effects in vitro stimulated metabolism and had a mitogenic effectin vivo. Finally, the adjuvant effect was tested by immunization in BALB/c mice. The major effect was obtainedwith NP+ liposomes. Accordingly, we also demonstrated that NP+ liposomes injected into the dermis producedan outstanding inflammatory reaction, showing the histopathological characteristics of an inoculationgranuloma. Thus, positive charge would play an important role in the immunoadjuvant effect of liposomesby conferring them cytotoxic capacity.