Sterically stabilized liposomes bearing anti-HLA-DR antibodies for targeting the primary cellular reservoirs of HIV-1.
The ability of liposomes bearing anti-HLA-DR Fab' fragments at the end termini of polyethyleneglycol chains (sterically stabilized immunoliposomes) to target HLA-DR expressing cells and increase the accumulation of liposomes into lymphoid organs has been evaluated and compared to that of conventional liposomes, sterically stabilized liposomes and conventional immunoliposomes after a single subcutaneous injection to mice. The accumulation of sterically stabilized liposomes in lymph nodes was higher than that of conventional liposomes. Sterically stabilized immunoliposomes accumulated much better than conventional immunoliposomes in all tissues indicating that the presence of PEG has an important effect on the uptake of immunoliposomes by the lymphatic system. Fluorescence microscopy studies showed that sterically stabilized liposomes are mainly localized in macrophage-rich areas such as the subcapsular region of lymph nodes and in the red pulp and marginal zone of the spleen. In contrast, sterically stabilized immunoliposomes mostly accumulated in the cortex in which follicles are located and in the white pulp of the spleen. As the human HLA-DR determinant of the major histocompatibility complex class II is expressed on activated CD4+ T lymphocytes and antigen presenting cells such as monocyte/macrophages and dendritic cells, known as the cellular reservoirs of HIV-1, liposomes bearing anti-HLA-DR antibodies constitute an attractive approach to concentrate drugs in HIV-1 reservoirs and improve their therapeutic effect.
Bestman-Smith
J
J
Centre de Recherche en Infectiologie, Centre Hospitalier Universitaire de Québec, Pavillon CHUL, 2705 Blvd Laurier, G1V 4G2, Québec, QC, Canada.
Gourde
P
P
Désormeaux
A
A
Tremblay
M J
MJ
Bergeron
M G
MG
D000818:Animals; D000906:Antibodies / Q000008:administration & dosage* / Q000276:immunology; D002232:Carbocyanines / Q000737:chemistry; D016503:Drug Delivery Systems; D005260:Female; D005434:Flow Cytometry; D005456:Fluorescent Dyes; D015497:HIV-1; D006684:HLA-DR Antigens / Q000276:immunology*; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D066298:In Vitro Techniques; D008081:Liposomes / Q000032:analysis / Q000737:chemistry / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology; D008221:Lymphoid Tissue / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008809:Mice, Inbred C3H; D008856:Microscopy, Fluorescence; D011092:Polyethylene Glycols / Q000737:chemistry; D013154:Spleen / Q000276:immunology; D014018:Tissue Distribution
D000906:Antibodies; D002232:Carbocyanines; D005456:Fluorescent Dyes; D006684:HLA-DR Antigens; D007140:Immunoglobulin Fab Fragments; D008081:Liposomes; D011092:Polyethylene Glycols; C024286:3,3'-dioctadecylindocarbocyanine