Doxorubicin entrapped within liposome-associated antigens results in a selective inhibition of the antibody response to the linked antigen.
The generation of an immune response can dramatically alter the circulation lifetime of a targeted liposome, particularly when the response is generated against the surface-coupled ligand. Following repeated administrations, rapid elimination of the carrier system is observed, thereby limiting potential applications for targeted liposomes in a therapeutic setting. In this study, we have investigated whether the encapsulation of a toxic drug within the carrier could prevent an immune response against a surface-bound protein. Liposome clearance and humoral immune response were monitored throughout multiple administrations of liposomes containing doxorubicin with surface-conjugated ovalbumin. The results show that low doses of encapsulated doxorubicin can prevent humoral immunity against repeated administration of liposomes conjugated with ovalbumin. The immunosuppressive effect was specific for the ovalbumin coupled to the liposome surface. This selective suppression of immunity against a surface conjugated protein could prove advantageous for safe repeated administration of protein containing liposomal systems.
Oja
C
C
Liposome Research Unit, Department of Biochemistry, University of British Columbia, 2146 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada.
Tardi
P
P
Schutze-Redelmeier
M
M
Cullis
P R
PR
D000818:Animals; D000937:Antigen-Antibody Reactions / Q000276:immunology; D000941:Antigens / Q000008:administration & dosage* / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage* / Q000276:immunology; D016503:Drug Delivery Systems; D005260:Female; D006863:Hydrogen-Ion Concentration; D007166:Immunosuppressive Agents / Q000276:immunology*; D007275:Injections, Intravenous; D008081:Liposomes; D051379:Mice; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D011510:Proteolipids / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology
D000941:Antigens; D007166:Immunosuppressive Agents; D008081:Liposomes; D011510:Proteolipids; C020485:proteoliposomes; D004317:Doxorubicin; D010047:Ovalbumin