A novel approach for delivery of enzyme drugs: preliminary demonstration of feasibility and utility in vitro.
A novel heparin/protamine-based approach for delivery of enzyme drugs without associated toxic effects has been proposed. This approach would allow an enzyme drug to be administered in an inactive (i.e. pro-drug) form and then released at the target site in an active form using protamine as the triggering agent. The pro-drug and the triggered release features of this approach would permit the enzyme drug to act specifically and only on its target substrates while sparing normal substrates, thereby alleviating unwanted toxic effects. The in vitro feasibility of the approach has been successfully demonstrated using trypsin as the model protease drug. In addition, the utility of the approach has also been demonstrated by applying the system in delivering streptokinase, one of the most widely used clinical drugs in thrombolytic therapy. This approach may open up the possibility of developing a wide range of new catalytic drugs that are initially thought to be impossible for therapeutic use due to their potent toxic effects.
College of Pharmacy, The University of Michigan, 428 Church Street, Ann Arbor, MI 48109-1065, USA.
J F
JF
Liang
Y T
YT
Li
V C
VC
Yang
D001399:Azure Stains / Q000008:administration & dosage*; D016503:Drug Delivery Systems / Q000379:methods*; D004798:Enzymes / Q000008:administration & dosage*; D005240:Feasibility Studies; D005343:Fibrinolytic Agents / Q000008:administration & dosage*; D006493:Heparin / Q000008:administration & dosage*; D011355:Prodrugs / Q000008:administration & dosage; D013300:Streptokinase / Q000008:administration & dosage; D014357:Trypsin / Q000008:administration & dosage
D001399:Azure Stains; D004798:Enzymes; D005343:Fibrinolytic Agents; D011355:Prodrugs; D006493:Heparin; D013300:Streptokinase; D014357:Trypsin; C025818:Azure A