Tissue selective drug delivery utilizing carrier-mediated transport systems.
This paper describes some successful examples of a tissue selective drug delivery by utilizing specialized transporter(s) expressed in the targeted tissue cells. These are as follows: (1) oral delivery via H(+)/oligopeptide transporter, rat or human Pept1, in the intestine for beta-lactam antibiotics and a newly synthesized dipeptide, L-dopa-L-phenylalanine; (2) tumor cell specific delivery via the newly discovered H(+)/oligopeptide transporter(s) expressed in human fibrosarcoma cell line HT-1080 for model oligopeptides, glycylsarcosine and carnosine; (3) oral and hepatic delivery via an H(+)/monocarboxylate transporter in the intestine and an organic anion transporter in the liver for HMG-CoA reductase inhibitor, pravastatin; and (4) lung selective delivery via some type of transporter and avoidance of transfer into the brain via P-glycoprotein at the blood-brain barrier for a new quinolone antibacterial, HSR-903.
Tsuji
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Department of Pharmacobio-Dynamics, Faculty of Pharmaceutical Sciences, Kanazawa University, 13-1 Takara-machi, Kanazawa, Japan. tsuji@kenroku.kanazawa-u.ac.jp
D000818:Animals; D000900:Anti-Bacterial Agents / Q000378:metabolism*; D001692:Biological Transport; D001921:Brain / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D004151:Dipeptides / Q000378:metabolism*; D016503:Drug Delivery Systems; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D007769:Lactams; D008099:Liver / Q000378:metabolism; D009928:Organ Specificity; D000074011:Peptide Transporter 1; D017035:Pravastatin / Q000378:metabolism; D051381:Rats; D027981:Symporters; D014407:Tumor Cells, Cultured; D014982:Xenopus laevis
D000900:Anti-Bacterial Agents; D002352:Carrier Proteins; D004151:Dipeptides; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007769:Lactams; D000074011:Peptide Transporter 1; C082186:SLC15A1 protein, human; C489940:Slc15a1 protein, rat; D027981:Symporters; C093694:hydrogen-coupled oligopeptide transporter PepT2; D017035:Pravastatin