Drugs and gene carrier particles that rapidly move through mucous barriers

Abstract

The invention generally relates to polymeric particles suitable for transporting bioactive agents across mucosal barriers. The invention also relates to methods of making and using those polymeric particles.

1 - 25 . (canceled) 
     
     
         26 . A method for treating, preventing, or diagnosing a condition in a patient, comprising administering to the patient a pharmaceutical composition comprising a polymeric particle and a pharmaceutically acceptable carrier, wherein the polymeric particle comprises a pharmaceutically acceptable polymer core, a bioactive agent, and a surface-altering agent disposed on the surface of the polymer core,
 wherein the surface-altering agent enhances the average rate at which the particle moves in mucus by at least 5-fold compared to the same particle except without a surface-altering agent disposed on the surface,   wherein the surface-altering agent reduces the overall charge on the surface of the polymeric particle and enhances the hydrophilicity of the surface of the polymeric particle compared to the same particle except without a surface-altering agent disposed on the surface,   wherein the surface-altering agent comprises polyethylene glycol having a molecular weight of about 2-3 kDa, and   wherein the polymeric particle is less than about 1 micron in diameter.   
     
     
         27 . The method of  claim 26 , wherein the bioactive agent is encapsulated in the polymer core. 
     
     
         28 . The method of  claim 26 , wherein the bioactive agent is disposed on the surface of the polymeric particle. 
     
     
         29 . The method of  claim 26 , wherein the bioactive agent is covalently coupled to the polymer core. 
     
     
         30 . The method of  claim 26 , wherein the pharmaceutically acceptable polymer is a poly(D,L-lactic-co-glycolic) acid, a polyethylenimine, dioleyltrimethylammoniumpropane, dioleyl-sn-glycerolphosphoethanolamine, a poly(anhydride), a polymer formed from clinically approved monomers, or a combination of dioleyltrimethylammoniumpropane and dioleyl-sn-glycerolphosphoethanolamine. 
     
     
         31 . The method of  claim 30 , wherein the clinically approved monomers are monomers of sebacic acid, 1,3-bis(carboxyphenoxy)propane, and/or ethylene glycol. 
     
     
         32 . The method of  claim 26 , wherein the bioactive agent is a therapeutic agent or an imaging agent. 
     
     
         33 . The method of  claim 32 , wherein the therapeutic agent is a DNA, an RNA, a small molecule, a peptidomimetic, or a protein. 
     
     
         34 . The method of  claim 32 , wherein the bioactive agent is an imaging agent; and the imaging agent is a diagnostic agent. 
     
     
         35 . The method of  claim 32 , wherein the bioactive agent is an imaging agent; and the imaging agent further comprises a detectable label. 
     
     
         36 . The method of  claim 26 , wherein the polymeric particle further comprises a targeting moiety. 
     
     
         37 . The method of  claim 26 , wherein the polymeric particle further comprises an adjuvant. 
     
     
         38 . The method of  claim 26 , wherein the surface-altering agent is a cationic surfactant. 
     
     
         39 . The method of  claim 38 , wherein the cationic surfactant is dimethyldioctadecylammonium bromide. 
     
     
         40 . The method of  claim 26 , wherein the surface-altering agent is polyethylene glycol having a molecular weight of about 2-3 kDa. 
     
     
         41 . The method of  claim 26 , wherein the polymeric particle is less than 200 nm in diameter. 
     
     
         42 . The method of  claim 26 , wherein the polymeric particle passes through a mucosal barrier at a greater rate than a polystyrene particle of the same size. 
     
     
         43 . The method of  claim 26 , wherein the bioactive agent is a DNA, and wherein the polymeric particle comprising the DNA transfects a cell more efficiently than does naked DNA. 
     
     
         44 . The method of  claim 26 , wherein the polymeric particle in the pharmaceutical composition passes through a mucosal barrier in the patient. 
     
     
         45 . The method of  claim 26 , wherein the polymeric particle is less than about 500 nm in diameter. 
     
     
         46 . A method for treating, preventing, or diagnosing a condition in a patient in need thereof, comprising administering to the patient an effective amount of a particle,
 wherein   the particle comprises a pharmaceutically acceptable core, a bioactive agent, and a surface-altering agent disposed on the surface of the core,   the surface-altering agent enhances the average rate at which the particle moves in mucus by at least 5-fold compared to the same particle except without a surface-altering agent disposed on the surface,   the surface-altering agent reduces the overall charge on the surface of the particle and enhances the hydrophilicity of the surface of the particle compared to the same particle except without a surface-altering agent disposed on the surface,   the surface-altering agent comprises polyethylene glycol having a molecular weight of about 2-3 kDa, and   the particle is less than about 1 micron in diameter.   
     
     
         47 . The method of  claim 46 , wherein the method is a method of treating a condition in a patient. 
     
     
         48 . The method of  claim 47 , wherein the condition is an ophthalmic condition.