Drugs and Gene Carrier Particles That Rapidly Move Through Mucous Barriers
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 . 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 that renders the surface of the polymeric particle mucus resistant and/or enhances the average rate at which the particles or a fraction of the particles moves in mucus.
2 . The method of claim 1 , wherein the bioactive agent is encapsulated in the polymer core.
3 . The method of claim 1 , wherein the bioactive agent is disposed on the surface of the polymeric particle.
4 . The method of claim 1 , wherein the bioactive agent is covalently coupled to the polymer core.
5 . The method of claim 1 , wherein the pharmaceutically acceptable polymer is a poly(D,L-lactic-co-glycolic) acid, polyethylenimine, dioleyltrimethylammoniumpropane/dioleyl-sn-glycerolphosphoethanolamine, poly(anhydrides), or a polymer formed from clinically approved monomers.
6 . The method of claim 5 , wherein the clinically approved monomers are monomers of sebacic acid, 1,3-bis(carboxyphenoxy)propane, and/or ethylene glycol.
7 . The method of claim 1 , wherein the bioactive agent is a therapeutic agent or an imaging agent.
8 . The method of claim 7 , wherein the therapeutic agent is a DNA, an RNA, a small molecule, a peptidomimetic, or a protein.
9 . The method of claim 7 , wherein the imaging agent is a diagnostic agent.
10 . The method of claim 7 , wherein the imaging agent further comprises a detectable label.
11 . The method of claim 1 , wherein the polymeric particle further comprises a targeting moiety.
12 . The method of claim 1 , wherein the polymeric particle further comprises an adjuvant.
13 . The method of claim 1 , wherein the surface-altering agent is a cationic surfactant.
14 . The method of claim 13 , wherein the cationic surfactant is dimethyldioctadecylammonium bromide.
15 . The method of claim 1 , wherein the surface-altering agent enhances hydrophilicity of the surface of the polymeric particle.
16 . The method of claim 15 , wherein the surface-altering agent is polyethylene glycol.
17 . The method of claim 1 , wherein the polymeric particle is less than 200 nm in diameter.
18 . The method of claim 1 , wherein the polymeric particle passes through a mucosal barrier at a greater rate than a polystyrene particle of a similar size.
19 . The method of claim 1 , wherein the bioactive agent is a DNA, and wherein the polymeric particle comprising the DNA transfects a cell more efficiently than does naked DNA.
20 - 24 . (canceled)
25 . The method of claim 1 , wherein the polymeric particle in the pharmaceutical composition passes through a mucosal barrier in the patient.