In vitro and in vivo comparison of immunoliposomes made by conventional coupling techniques with those made by a new post-insertion approach.
Ligand-targeted liposomes have the potential to increase the therapeutic efficacy of antineoplastic agents. Recently, a combinatorial approach to the preparation of ligand-targeted liposomes has been developed, termed the post-insertion technique, which will facilitate the production of targeted liposomes. In this paper, Stealth immunoliposomes (SIL) coupled to anti-CD19 made by either a conventional coupling technique (SIL[anti-CD19]), or by the post-insertion technique (PIL[anti-CD19], were compared with respect to their in vitro binding and cytotoxicity and their ability to improve in vivo survival in tumor-bearing mice. The in vitro binding and uptake of PIL[anti-CD19] by CD19-expressing, B-cell lymphoma (Namalwa) cells was similar to that of SIL[anti-CD19] and both were significantly higher than binding of non-targeted liposomes (SL). In addition, no significant differences were found between the respective in vitro cytotoxicities of doxorubicin-loaded PIL[anti-CD19] or SIL[anti-CD19], or in their in vivo therapeutic efficacy in a murine model of human B-lymphoma. Overall, the results demonstrate that the post-insertion technique is a simple, flexible and effective means for preparing targeted liposomal drugs for clinical applications.
Iden
D L
DL
Department of Pharmacology, University of Alberta, Edmonton, AB, Canada T6G 2H7.
Allen
T M
TM
D000818:Animals; D000911:Antibodies, Monoclonal; D018941:Antigens, CD19 / Q000276:immunology; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D002051:Burkitt Lymphoma / Q000188:drug therapy; D004317:Doxorubicin / Q000008:administration & dosage / Q000627:therapeutic use; D004337:Drug Carriers; D005260:Female; D008024:Ligands; D008081:Liposomes / Q000138:chemical synthesis / Q000276:immunology* / Q000493:pharmacokinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D008823:Micelles; D011956:Receptors, Cell Surface / Q000276:immunology; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D018941:Antigens, CD19; D000970:Antineoplastic Agents; D004337:Drug Carriers; D008024:Ligands; D008081:Liposomes; D008823:Micelles; D011956:Receptors, Cell Surface; D004317:Doxorubicin