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Enhanced intracellular delivery of methotrexate by a receptor-mediated process.

DIR@IMTECH: CSIR-Institute of Microbial Technology

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Title Enhanced intracellular delivery of methotrexate by a receptor-mediated process.
 
Creator Mukhopadhyay, A
Basu, S K
 
Subject QD Chemistry
 
Description In the present investigation we have described a method of enhancing the uptake of methotrexate by macrophages. This enhanced uptake was mediated by endocytosis through the "scavenger receptor" system which recognized maleylated bovine serum albumin. Experimental evidence showed that macrophages internalized methotrexate coupled to maleylated bovine serum albumin through a saturable process at 37 degrees C leading to an eightfold higher concentration of cell-associated methotrexate compared to the free drug. Following uptake, the drug conjugate was degraded in the lysosomes leading to intracellular release of a pharmacologically active form of methotrexate. When administered to macrophages infected with Leishmania mexicana amazonensis, the drug conjugate could eliminate the intracellular amastigotes more efficiently than the free drug. The leishmanicidal effect of the drug conjugate was inhibited in the presence of excess maleylated bovine serum albumin and lysosomal inhibitors such as chloroquine and monensin. Addition of folinic acid to the medium also prevented the elimination of the amastigotes by the drug conjugate. These results suggested that the scavenger receptor-mediated endocytosis of the drug conjugate led to enhanced transport and intracellular release of a pharmacologically active form of methotrexate resulting in more efficient killing of the amastigotes compared to the free drug. This modality of delivering drugs selectively to macrophages might have utility in the chemotherapy of macrophage-associated disorders in general.
 
Publisher Elsevier Science
 
Date 1990-10
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://crdd.osdd.net/open/432/1/basu1990.pdf
Mukhopadhyay, A and Basu, S K (1990) Enhanced intracellular delivery of methotrexate by a receptor-mediated process. Biotechnology and applied biochemistry, 12 (5). pp. 529-36. ISSN 0885-4513
 
Relation http://crdd.osdd.net/open/432/