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US20090269397: TARGETED AND HIGH DENSITY DRUG LOADED POLYMERIC MATERIALS
33 Claims, 5 Drawings
Polymeric delivery devices have been developed which combine high loading/high density of molecules to be delivered with the option of targeting. As used herein, “high density” refers to microparticles having a high density of ligands or coupling agents, which is in the range of 1000-10,000,000, more preferably between 10,000 and 1,000,000 ligands per square micron of microparticle surface area. A general method for incorporating molecules into the surface of biocompatible polymers using materials with an HLB of less than 10, more preferably less than 5, such as fatty acids, has been developed. Because of its ease, generality and flexibility, this method has widespread utility in modifying the surface of polymeric materials for applications in drug delivery and tissue engineering, as well other fields. Targeted polymeric microparticles have also been developed which encapsulate therapeutic compounds such as drugs, cellular materials or components, and antigens, and 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. Polymeric microparticles for delivery of a therapeutic, nutritional, diagnostic or prophylactic agent incorporated in a high density on or within the microparticles, the microparticles comprising ligands present in a density of between about which is preferably in the range of 1,000 to 10,000,000, more preferably 10,000-1,000.000, ligands per square micron of microparticle surface area.
- 28. A method for making a microparticle for delivery of a therapeutic, nutritional, diagnostic or prophylactic agent comprising
Providing a solution of a hydrophobic polymer or the polymer in liquid form,
Adding materials with an HLB of less than 10, more preferably less than 5, to the polymer, which insert into the surface of the microparticles when the polymer is solidified to form microparticles under conditions wherein one end of the material with an HLB of less than 10 inserts into the polymer and the other extends outwardly from the polymeric surface of the microparticle.
- 32. Microparticles formed of a hydrophobic or lipophilic polymer with a first end of a material with an HLB of less than 10 as a ligand interspersed therein and a second end of the material with an HLB of less than 10 facing outwardly from the surface of the microparticles.
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