Relationship between the adjuvant and cytotoxic effects of the positive charges and polymerization in liposomes

Abstract

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.

Keywords::

• Polymerizable liposomes
• cationic lipids
• immunoadjuvant
• cytotoxicity
• vaccine

Acknowledgments

The authors would like to thank Dr Oscar D. Bustuoabad Ph.D for his invaluable advice, support, and contribution to the ideas discussed in this article.

Declaration of interest

This research was supported by the Comisión Nacional de Investigaciones Científicas and Técnicas (CONICET) and Universidad Nacional de Quilmes (Buenos Aires, Argentina).