ENHANCEMENT OF POLYPEPTIDE AND PROTEIN-ABSORPTION BY MACROMOLECULAR CARRIERS VIA ENDOCYTOSIS AND TRANSCYTOSIS .3.
被引:54
作者:
SHEN, WC
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机构:John Stauffer Pharmaceutical Sciences Center, Department of Pharmaceutical Sciences, University of Southern California School of Pharmacy, Los Angeles, CA
SHEN, WC
WAN, JS
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机构:John Stauffer Pharmaceutical Sciences Center, Department of Pharmaceutical Sciences, University of Southern California School of Pharmacy, Los Angeles, CA
WAN, JS
EKRAMI, H
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机构:John Stauffer Pharmaceutical Sciences Center, Department of Pharmaceutical Sciences, University of Southern California School of Pharmacy, Los Angeles, CA
EKRAMI, H
机构:
[1] John Stauffer Pharmaceutical Sciences Center, Department of Pharmaceutical Sciences, University of Southern California School of Pharmacy, Los Angeles, CA
MACROMOLECULE;
DRUG CARRIER;
TRANSCELLULAR TRANSPORT;
INTRACELLULAR PROCESSING;
TRANSPORT ENHANCEMENT;
PROTEIN MODIFICATION;
D O I:
10.1016/0169-409X(92)90016-J
中图分类号:
R9 [药学];
学科分类号:
1007 ;
摘要:
Recent advances in biotechnology and the increasingly availability of proteins and of peptides with potential therapeutic applications have generated a renewed necessity for the controlled delivery of this class of macromolecules. Due to their large size and hydrophilic nature, these proteins and peptides are incapable of premeating cellular membranes without the assistance of specific cell-membrane transporters or carriers. Although cellular uptake of proteins is dependent upon endocytosis, passage through endothelial and epithelial barriers, i.e., transcytosis, will govern delivery from the site of administration to the site of action. The transport of proteins can be achieved by either modification of the native protein or attachment to receptor-specific or membrane-adsorptive carrier molecules. The design of an effective macromolecular drug carrier system requires an understanding of these intricate cellular transport and processing mechanisms. In some cases these processes can be manipulated in a pharmacological manner in order to improve significantly their transport. The exploitation of endocytotic and transcytotic processes is likely to become useful for the delivery of therapeutic proteins as well as other desirable macromolecules.