Methods of treatment with drug loaded polymeric materials

Abstract

Polymeric microparticles have been developed which encapsulate therapeutic compounds such as drugs, cellular materials or components, and antigens, and can have targeting ligands directly bound to the microparticle surface. Preferred applications include use in tissue engineering matrices, wound dressings, bone repair or regeneration materials, and other applications where the microparticles are retained at the site of application or implantation. Another preferred application is in the use of microparticles to deliver anti-proliferative agents to the lining of blood vessels following angioplasty, transplantation or bypass surgery to prevent or decrease restenosis, and in cancer therapy. In still another application, the microparticles are used to treat or prevent macular degeneration when administered to the eye, where agents such as complement inhibitors are administered.

1 . A method of treatment or prevention of undesirable proliferation of cells comprising administering at a site at or adjacent to a region of undesired proliferation microparticles delivering a high density of an anti-proliferative factor in an amount effective to prevent or decrease cellular proliferation. 
   
   
       2 . The method of  claim 1  wherein the undesired proliferation is restenosis arising from endothelial dysfunction. 
   
   
       3 . The method of  claim 1  comprising administering the microparticles at the time of or immediately following angioplasty, vessel grafting, tissue or organ transplantation, synthetic vessel implants, synthetic joint implants or other medical implants. 
   
   
       4 . The method of  claim 1  wherein the cells are endothelial cells, wherein the method is for the treatment or prevention of macular degeneration and the microparticles contain a high density of an anti-angiogenic, anti-proliferative or complement inhibitor in an amount effective to prevent or decrease vascularization of the retina when the microparticles are administered intraocularly. 
   
   
       5 . The method of  claim 1  wherein the agent is a cytotoxic, cytostatic, antiproliferative or anti-angiogenic agent and the microparticles are administered locally or regionally for the treatment of cancer. 
   
   
       6 . The method of  claim 1  wherein the microparticles further comprise ligands having bound thereto targeting or attachment molecules. 
   
   
       7 . The method of  claim 1  wherein the agent is a cytotoxic, cytostatic, antiproliferative or anti-angiogenic agent, the targeting molecules are specific for tumor cells and the microparticles are administered to a individual having the tumor cells. 
   
   
       8 . A method for inhibiting calcification of surgical implants, stents, prosthesis comprising implanting as part of or adjacent to the surgical implant, stent, or prosthesis microparticles comprising molecules inhibiting calcification. 
   
   
       9 . The method of  claim 8  wherein the molecules are osteopontin. 
   
   
       10 . A tissue engineering matrix, wound dressing, or medical implant comprising high density microparticles for delivery of a therapeutic, nutritional, diagnostic or prophylactic agent incorporated in a high density on or within the microparticle. 
   
   
       11 . The matrix of  claim 10  wherein the microparticles comprise ligands having a first end incorporated into the surface of the microparticle and a second end facing outwardly from the surface of the microparticle, the ligands being present in a high density on the surface of the microparticle and being bound to an agent to be delivered selected from the group consisting of therapeutic, nutritional, diagnostic and prophylactic agents, targeting and attachment molecules.