SPECIFIC ENHANCEMENT OF DRUG DELIVERY TO AKR LYMPHOMA BY ANTIBODY-TARGETED SMALL UNILAMELLAR VESICLES

  • 1 January 1984
    • journal article
    • research article
    • Vol. 44  (5) , 1880-1886
Abstract
Antibody targeting of drug-containing liposomes to specific cell populations provides the opportunity to improve cancer chemotherapy. The efficacy of targeted liposomes containing methotrexate-.gamma.-aspartate against 2 murine T-lymphomas, AKR/J SL2 and R1.1 was reported. Both large and small unilamellar vesicles conjugated to anti-Thy-1.1 antibody associated with AKR lymphoma cells in 10-fold greater amounts than nonconjugated liposomes or liposomes conjugated to a nonspecific antibody. Cell association was inhibited by 2 different anti-Thy-1.1 monoclonal antibodies, but not by nonspecific antibody. Vesicle size is the critical factor determining drug delivery of targeted liposomes to both AKR and R1.1 T-lymphoma cells. Although targeted large unilamellar vesicles (mean diameter, 0.45 .mu.m) specifically bind to lymphoma cells, they probably are not internalized, becuase they fail to enhance the efficacy of the drug for growth inhibition of either AKR or R1.1 cells. Drug encapsulated in targeted small unilemallar vesicles (mean diameter, 0.053 .mu.m) is up to 22 times more effective than free drug against AKR cells, and is 40 times more effective against R1.1 cells. The efficacy of small compared to large unilamellar vesicles was demonstrated using 2 different target antigens. Thy-1.1 for AKr cells and H-2Kk for R1.1 cells. These experiments estabish a system which can be used to test the antitumor efficacy of targeted liposomes against AKR/J SL2 lymphoma implanted in AKR/Cu mice.