Enhanced lymph node delivery and immunogenicity of hepatitis B surface antigen entrapped in galactosylated liposomes

Abstract

The purpose of this work is to increase the lymph node delivery and the immunogenicity of hepatitis B surface antigen (HBsAg) in vivo. HBsAg was entrapped in the dried liposomes with their surfaces modified with galactose. Pharmacokinetics and organ distribution of free HBsAg alone, HBsAg mixed with aluminum phosphate, HBsAg entrapped in ungalactosylated liposomes and galactosylated liposomes (GaIL) were studied. For each sample, the anti-HBsAg titres were measured by RIA. Most HBsAg in Ga1L existed in an antibody-available form. In rats, HBsAg in GaIL administered to right thigh muscles, resided in the injection sites longer than did free HBsAg alone or HBsAg mixed with aluminum phosphate. Also, Ga1L delivered higher amounts of HBsAg to the regional lymph nodes than did other formulations: the area under the concentration-time curve of HBsAg in the regional lymph nodes given in Ga1L was 16, 2.4, and 2.2-fold higher than that in free form, aluminum phosphate mixture and ungalactosylated liposomes, respectively. The immunogenicity of HBsAg given in Ga1L showed a good correlation to its enhanced delivery to the lymph nodes. HBsAg in Ga1L boosted the formation of antibodies 40-fold higher than did free HBsAg, whereas HBsAg mixed with aluminum phosphate and HBsAg in ungalactosylated liposomes increased the titre by 21- and 13-fold, respectively. Taken together, it is concluded that the galactosylated liposomes can target HBsAg to the regional lymph nodes, rich in the antigen-presenting cells and enhance the immunogenicity of HBsAg more efficiently than do the conventional aluminum phosphate or the ungalactosylated liposome formulations.