Receptor-mediated endocytosis of macromolecular conjugates in selective drug delivery.
IR@IMTECH: CSIR-Institute of Microbial Technology, Chandigarh
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| Title |
Receptor-mediated endocytosis of macromolecular conjugates in selective drug delivery.
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| Creator |
Basu, S K
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| Subject |
QD Chemistry
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| 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 37OC 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 ofthe 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 ofdelivering drugs selectively to macrophages might have
utility in the chemotherapy of macrophage-associated disorders in general.
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| Publisher |
Portland Press Ltd.
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| Date |
1990-11-01
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| Type |
Article
PeerReviewed |
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| Format |
application/pdf
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| Identifier |
http://crdd.osdd.net/open/430/1/basu1990.pdf
Basu, S K (1990) Receptor-mediated endocytosis of macromolecular conjugates in selective drug delivery. Biochemical pharmacology, 40 (9). pp. 1941-6. ISSN 0006-2952 |
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| Relation |
http://www.sciencedirect.com/science/article/pii/0006295290902227
http://crdd.osdd.net/open/430/ |
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