Uniform Field Magnetization and Targeting of Therapeutic Formulations

Abstract

Systems and methods for magnetic targeting of therapeutic particles are provided. Therapeutic particles comprise one or more magnetic or magnetizable materials and at least one therapeutic agent. Therapeutic particles are specifically targeted using uniform magnetic fields capable of magnetizing magnetizable materials, and can be targeted to particular locations in the body, or can be targeted for capture, containment, and removal. Also provided are bioresorbable nanoparticles prepared without the use of organic solvents, and methods for therapeutically using such bioresorbable nanoparticles.

1 . A method for preparing nanoparticles comprising the steps of:
 (a) providing a first aqueous solution comprising a water soluble salt of a mono-carboxylic fatty acid or a lipid mono-phosphate; and   (b) adding to the first aqueous solution a second aqueous solution comprising a polyvalent biocompatible cation;   wherein the step of adding is performed in the presence of at least one colloidal stabilizer.   
     
     
         2 . The method of  claim 1 , wherein the first or second aqueous solution further comprises at least one therapeutic agent. 
     
     
         3 . The method of  claim 1 , wherein the first aqueous solution further comprises magnetic nanocrystals. 
     
     
         4 . The method of  claim 2 , further comprising forming the magnetic nanocrystals in the first aqueous solution. 
     
     
         5 . The method of  claim 1 , wherein the first aqueous solution comprises said water soluble salt of a mono-carboxylic fatty acid. 
     
     
         6 . The method of  claim 4 , wherein the water soluble salt of the mono-carboxylic fatty acid is sodium oleate. 
     
     
         7 . The method of  claim 1 , wherein the first aqueous solution comprises said water soluble salt of a lipid mono-phosphate. 
     
     
         8 . The method of  claim 7 , wherein the water soluble salt of the lipid mono-phosphate is α-tocopheryl phosphate disodium salt. 
     
     
         9 . The method of  claim 7 , wherein the water soluble salt of the lipid mono-phosphate is oeyl phosphate disodium salt. 
     
     
         10 . The method of  claim 1 , wherein the stabilizer is albumin. 
     
     
         11 . The method of  claim 1 , wherein the stabilizer comprises a non-ionic surfactant. 
     
     
         12 . The method of  claim 11 , wherein the non-ionic surfactant is selected from the group consisting of polyethylene oxide, ethylene oxide/propylene oxide block co-polymers, and ethoxylated fatty acid esters of sorbitan. 
     
     
         13 . The method of  claim 1 , wherein the polyvalent biocompatible cation is a polyvalent metal cation. 
     
     
         14 . The method of  claim 1 , wherein the polyvalent biocompatible cation is Ca ++ . 
     
     
         15 . The method of  claim 1 , wherein the polyvalent biocompatible cation is Zn ++ . 
     
     
         16 . The method of  claim 1 , wherein the polyvalent biocompatible cation is Mg ++ . 
     
     
         17 . The method of  claim 1 , wherein the second aqueous solution further comprises at least one cationic polypeptide. 
     
     
         18 . The method of  claim 17 , wherein the cationic peptide is poly-L-arginine. 
     
     
         19 . The method of  claim 2 , wherein the at least one therapeutic agent is taxol or all-trans retinoic acid. 
     
     
         20 . The method of  claim 2 , wherein the at least one therapeutic agent comprises an adenovirus. 
     
     
         21 . The method of  claim 2 , wherein at least one therapeutic agent is a nucleic acid. 
     
     
         22 . The method of  claim 2 , wherein the at least one therapeutic agent is a regulatory nucleic acid. 
     
     
         23 . The method of  claim 2 , wherein the at least one therapeutic agent is siRNA, shRNA, or mRNA. 
     
     
         24 . The method of  claim 2 , wherein the at least one therapeutic agent comprises paclitaxel. 
     
     
         25 . The method of  claim 2 , wherein the at least one therapeutic agent comprises an enzyme. 
     
     
         26 . The method of  claim 1 , wherein the at least one particle comprises magnetite. 
     
     
         27 . The method of  claim 1 , further comprising
 (c) attaching a therapeutic agent to the nanoparticles.   
     
     
         28 . The method of  claim 27 , wherein the therapeutic agent comprises a pharmaceutical, biomolecule, or cell. 
     
     
         29 . The method of  claim 27 , wherein the therapeutic agent is a cell. 
     
     
         30 . The method of  claim 29 , wherein the cell is an endothelial cell. 
     
     
         31 . The method of  claim 30 , wherein the endothelial cell is a vascular endothelium cell.