INVESTIGADORES
ALONSO Silvia Del Valle
artículos
Título:
Relationship between the adjuvant and cytotoxic effects of the positive charges and polymerization in liposomes
Autor/es:
JULIETA GASPARRI, LUCÍA SPERONI, NADIA SILVIA CHIARAMONI AND SILVIA DEL VALLE ALONSO
Revista:
JOURNAL OF LIPOSOME RESEARCH
Editorial:
TAYLOR & FRANCIS INC
Referencias:
Lugar: UK; Año: 2010 p. 1 - 10
ISSN:
0898-2104
Resumen:
<!-- /* Style Definitions */ p.MsoNormal, li.MsoNormal, div.MsoNormal {mso-style-parent:""; margin:0cm; margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:10.0pt; font-family:"Times New Roman"; mso-fareast-font-family:"Times New Roman"; mso-ansi-language:EN-US;} @page Section1 {size:612.0pt 792.0pt; margin:70.85pt 3.0cm 70.85pt 3.0cm; mso-header-margin:36.0pt; mso-footer-margin:36.0pt; mso-paper-source:0;} div.Section1 {page:Section1;} --> Vaccine development today encounters a main obstacle which is the need for effective adjuvants suitable for clinical trials. Aluminum salts, discovered 70 years ago, remain to be the only type of adjuvant currently approved by the US Food and Drug Administration. Liposomes represent an alternative approach to vaccine adjuvants. Herein we study 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 48-hour incubation. Similar results were obtained with cells from peritoneal cavity 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.