Orally Active, Cell-Penetrating Homing Peptide and Methods of Using Same

Abstract

Disclosed are compositions and methods useful for oral delivery of targeted therapies for pulmonary diseases, fibrotic disorders and cancer. The compositions and methods are based on peptide sequences that selectively bind to and home to diseased tissue and enable targeted therapies to affect a beneficial therapeutic result. The disclosed targeting is useful for oral delivery of therapeutic and detectable agents to diseased tissue in an animal.

What is claimed is: 
     
         1 . A composition comprising:
 a) an orally active targeting peptide comprising a sequence substantially identical to at least one member selected from the group consisting of SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6 and SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11 and SEQ ID NO: 12; and   (b) at least one therapeutic compound which conveys a measureable therapeutic benefit to a disease.   
     
     
         2 . The composition of  claim 1 , wherein the targeting peptide is animal, bacterial, viral or synthetic in origin. 
     
     
         3 . The composition of  claim 1 , wherein the disease is selected from the group consisting of pulmonary hypertension, interstitial lung disease, acute lung injury (ALI), acute respiratory distress syndrome (ARDS), sepsis, septic shock, sarcoidosis of the lung, pulmonary manifestations of connective tissue diseases, including systemic lupus erythematosus, rheumatoid arthritis, scleroderma, and polymyositis, dermatomyositis, bronchiectasis, asbestosis, berylliosis, silicosis, Histiocytosis X, pneumotitis, smoker's lung, bronchiolitis obliterans, the prevention of lung scarring due to tuberculosis and pulmonary fibrosis, other fibrotic diseases such as myocardial infarction, endomyocardial fibrosis, mediastinal fibrosis, myelofibrosis, retroperitoneal fibrosis, progressive massive fibrosis, pneumoconiosis, nephrogenic systemic fibrosis, keloid, arthrofibrosis, adhesive capsulitis, radiation fibrosis, fibrocystic breast condition, liver cirrhosis, hepatitis, liver fibrosis, nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, sarcoidosis of the lymph nodes, or other organs; inflammatory bowel disease, Crohn's disease, ulcerative colitis, primary biliary cirrhosis, pancreatitis, interstitial cystitis, chronic obstructive pulmonary disease, atherosclerosis, ischemic heart disease, vasculitis, neoplastic/metastatic/oncological diseases (including cancer), pneumoconiosis, autoimmune diseases, inflammatory diseases, angiogenic diseases, wound healing, infections, trauma injuries and systemic connective tissue diseases including systemic lupus erythematosus, rheumatoid arthritis, scleroderma, polymyositis, dermatomyositis, and diabetes. 
     
     
         4 . The composition of  claim 3 , wherein the disease is pulmonary hypertension. 
     
     
         5 . The composition of  claim 1 , wherein the at least one therapeutic compound is specific for the disease to be treated. 
     
     
         6 . The composition of  claim 5 , wherein the at least one therapeutic compound is selected from the group consisting of steroids, fibronectin, anticlotting drugs, anti-platelet function drugs, drugs which prevent smooth muscle cell growth on inner surface wall of vessel, heparin, heparin fragments, aspirin, Coumadin, tissue plasminogen activator (TPA), urokinase, hirudin, streptokinase, methotrexate, cisplatin, fluorouracil, Adriamycin), ascorbic acid, beta carotene, vitamin E, antimetabolites, thromboxane inhibitors, non-steroidal and steroidal anti-inflammatory drugs, beta channel blockers, calcium channel blockers, DNA fragments, RNA fragments, complete expression genes, antibodies, lymphokines, growth factors, prostaglandins, leukotrienes, laminin, elastin, collagen, integrins, insulin and GLP-1 agonists. 
     
     
         7 . The composition of  claim 6 , wherein the at least one therapeutic compound is a vasodilator. 
     
     
         8 . A method of preventing or treating a disease comprising the steps of:
 a) providing an orally active targeting peptide comprising a sequence substantially identical to at least one member selected from the group consisting of SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6 and SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11 and SEQ ID NO: 12; and   (b) providing at least one therapeutic compound which conveys a measureable therapeutic benefit to a disease;   (c) co-administering an oral composition comprising (a) and (b) to an animal in need thereof; and   (d) measuring the therapeutic benefit to the animal.   
     
     
         9 . The method of  claim 8 , wherein the targeting peptide is animal, bacterial, viral or synthetic in origin. 
     
     
         10 . The method of  claim 8 , wherein the disease is selected from the group consisting of pulmonary hypertension, interstitial lung disease, acute lung injury (ALI), acute respiratory distress syndrome (ARDS), sepsis, septic shock, sarcoidosis of the lung, pulmonary manifestations of connective tissue diseases, including systemic lupus erythematosus, rheumatoid arthritis, scleroderma, and polymyositis, dermatomyositis, bronchiectasis, asbestosis, berylliosis, silicosis, Histiocytosis X, pneumotitis, smoker's lung, bronchiolitis obliterans, the prevention of lung scarring due to tuberculosis and pulmonary fibrosis, other fibrotic diseases such as myocardial infarction, endomyocardial fibrosis, mediastinal fibrosis, myelofibrosis, retroperitoneal fibrosis, progressive massive fibrosis, pneumoconiosis, nephrogenic systemic fibrosis, keloid, arthrofibrosis, adhesive capsulitis, radiation fibrosis, fibrocystic breast condition, liver cirrhosis, hepatitis, liver fibrosis, nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, sarcoidosis of the lymph nodes, or other organs; inflammatory bowel disease, crohn's disease, ulcerative colitis, primary biliary cirrhosis, pancreatitis, interstitial cystitis, chronic obstructive pulmonary disease, atherosclerosis, ischemic heart disease, vasculitis, neoplastic/metastatic/oncological diseases (including cancer), pneumoconiosis, autoimmune diseases, inflammatory diseases, angiogenic diseases, wound healing, infections, trauma injuries and systemic connective tissue diseases including systemic lupus erythematosus, rheumatoid arthritis, scleroderma, polymyositis, dermatomyositis, and diabetes. 
     
     
         11 . The method of  claim 10 , wherein the disease is pulmonary hypertension. 
     
     
         12 . The method of  claim 8 , wherein the at least one therapeutic compound is specific for the disease to be treated. 
     
     
         13 . The method of  claim 12 , wherein the at least one therapeutic compound is selected from the group consisting of steroids, fibronectin, anticlotting drugs, anti-platelet function drugs, drugs which prevent smooth muscle cell growth on inner surface wall of vessel, heparin, heparin fragments, aspirin, Coumadin, tissue plasminogen activator (TP A), urokinase, hirudin, streptokinase, methotrexate, cisplatin, fluorouracil, Adriamycin), ascorbic acid, beta carotene, vitamin E, antimetabolites, thromboxane inhibitors, non-steroidal and steroidal anti-inflammatory drugs, beta channel blockers, calcium channel blockers, DNA fragments, RNA fragments, complete expression genes, antibodies, lymphokines, growth factors, prostaglandins, leukotrienes, laminin, elastin, collagen, integrins, insulin and GLP-1 agonists. 
     
     
         14 . The method of  claim 13 , wherein the at least one therapeutic compound is a vasodilator.