Method of drug delivery to interstitial regions of the myocardium

Abstract

A method of treating the heart and other body tissues by injecting a compound comprised of microsphere encapsulated macromolecule therapeutic agents into the myocardium, such that the microsphere size inhibits capillary transport of the compound but may permit lymphatic transport of the compound, and the compound releases therapeutic agents upon degradation of the microsphere. The compounds may be used in a method of treating the coronary arteries in which lymphatic transportable therapeutic agents are injected into the myocardium at a location distal to a target site in the coronary artery, after which they are taken up by the lymphatic vessels and transported proximally relative to the coronary artery, and migrate from the lymphatic vessel to the coronary blood vessel.

1 . A composition for treatment of body tissue comprising: 
 a plurality of microspheres for treatment of body tissue, said microspheres being degradable in the body;    wherein said microspheres comprise an outer layer and an inner core inside the outer layer;    wherein the outer layer comprises an anti-angiogenic agent that can enter the lymphatic system of a heart in a first time period; and    wherein the inner core comprises an angiogenic agent that can only enter the lymphatic system of the heart in a second time period subsequent to the first time period.    
     
     
         2 . The composition of  claim 1  wherein the microspheres have an initial diameter greater than 30 μm.  
     
     
         3 . The composition of  claim 1  wherein the microspheres have an initial diameter between about 50 μm to about 600 μm.  
     
     
         4 . A composition for treatment of body tissue comprising: 
 a first group of microspheres sized to permit entry into the lymphatic system of the heart in a first time period; and    a second group of microspheres sized to inhibit entry into the lymphatic system of the heart in the first time period and permit entry into the lymphatic system of the hear in a subsequent time period    wherein the first group of microspheres comprises an anti-angiogenic agent and the second group of microspheres comprises an angiogenic agent    wherein the first group and second group of microspheres are degradable in the body.