Coated controlled release polymer particles as efficient oral delivery vehicles for biopharmaceuticals

Abstract

A composition for delivering an active agent to a patient. The composition includes a polymer core encapsulating the active agent and a mucoadhesive coating disposed about the core. The polymer may include covalently linked poly(ethylene glycol) chains, and the mucoadhesive coating may be selected to facilitate transfer of the particle through the intestinal mucosa. A molecular weight and cross-link density of the polymer may be selected such that the polymer core will decompose in a predetermined time interval. The fraction of the dose of the drug entering the system at circulation during the predetermined time interval may be between about 0.25% and about 25%. The composition may be formulated as a plurality of nanoparticles or microparticles that are combined with a pharmaceutically acceptable carrier to produce an edible or inhalable drug product.

What is claimed is: 
     
         1 . An oral composition comprising:
 a plurality of nanoparticles having a diameter between about 10 nm and 1,000 nm,   the nanoparticles comprising
 amphiphilic block co-polymer core encapsulating a therapeutic, diagnostic, or prophylactic agent, and 
 a mucoadhesive coating, the coating being present on the surface of the core and interacting with the amphiphilic block co-polymer through one or more of covalent interactions, affinity interactions, metal coordination, physical adsorption, host-guest interactions, and hydrogen bonding interactions, to form a coated nanoparticle; and 
   a pharmaceutically acceptable carrier.   
     
     
         2 . The composition of  claim 1 , further comprising a targeting agent disposed under the mucoadhesive coating. 
     
     
         3 . The composition of  claim 2 , further comprising an intermediate layer disposed between the targeting agent and the mucoadhesive coating. 
     
     
         4 .- 5 . (canceled) 
     
     
         6 . The composition of  claim 3 , wherein the intermediate layer comprises a biodegradable polymer. 
     
     
         7 . The composition of  claim 2 , wherein the targeting agent is disposed at a surface portion of the polymer core. 
     
     
         8 . The composition of  claim 2 , wherein the targeting agent is disposed at a surface portion of the polymer core and is also disposed at an interior portion of the polymer core. 
     
     
         9 . The composition of  claim 2 , wherein the targeting agent is selected from the group consisting of nucleic acid aptamers, growth factors, hormones, cytokines, interleukins, antibodies, integrins, fibronectin receptors, p-glycoprotein receptors, and cell binding sequences. 
     
     
         10 .- 11 . (canceled) 
     
     
         12 . The composition of  claim 1 , wherein the mucoadhesive coating interacts with the core through hydrogen bonding interactions, covalent interactions, or a combination thereof. 
     
     
         13 . The composition of  claim 1 , wherein the core comprises PEGylated poly(lactic acid). 
     
     
         14 . The composition of  claim 1 , wherein the core comprises poly(alkylene glycol). 
     
     
         15 . The composition of  claim 14 , wherein the poly(alkylene glycol) is selected from the group consisting of poly(ethylene glycol) and poly(propylene glycol). 
     
     
         16 . The composition of  claim 14 , wherein the poly(alkylene glycol) has a molecular weight between about 100 and about 7000 Daltons. 
     
     
         17 .- 20 . (canceled) 
     
     
         21 . The composition of  claim 1 , wherein the amphiphilic block co-polymer comprises a biodegradable polymer is selected from poly(arylates), poly(anhydrides), poly(hydroxy acids), polyesters, poly(lactic acid), poly(glycolic acid), poly(ortho esters), polycarbonates, poly(propylene fumerates), poly(caprolactones), polyamides, polyphosphazenes, polyamino acids, polyethers, polyacetals, polylactides, polyhydroxyalkanoates, polyglycolides, polyketals, polyesteramides, poly(dioxanones), polyhydroxybutyrates, polyhydroxyvalyrates, polycarbonates, polyorthocarbonates, poly(vinyl pyrrolidone), biodegradable polycyanoacrylates, polyalkylene oxalates, polyalkylene succinates, poly(malic acid), poly(methyl vinyl ether), poly(ethylene imine), poly(acrylic acid), poly(maleic anhydride), biodegradable polyurethanes, polysaccharides, PEG-functionalized derivatives of the above, co-polymers of the above, adducts of the above, and mixtures of the above. 
     
     
         22 . The composition of  claim 1 , wherein the amphiphilic block co-polymer comprises a non-biodegradable polymer is selected from the group consisting of polystyrene, polyesters, non-biodegradable polyurethanes, polyureas, poly(vinyl alcohol), polyamides, poly(tetrafluoroethylene), poly(ethylene vinyl acetate), polypropylene, polyacrylate, non-biodegradable polycyanoacrylates, polymethacrylate, poly(methyl methacrylate), polyethylene, polypyrrole, polyanilines, polythiophene, poly(ethylene oxide), PEG-functionalized derivatives of the above, co-polymers of the above, adducts of the above, and mixtures of the above. 
     
     
         23 . The composition of  claim 1 , wherein the coating comprises poly(ethylene imine), lecithin, polycarboxylic acids, poly(acrylic acids), polysaccharides, polypeptides, co-polymers of the above, or any combination of the above. 
     
     
         24 . The composition of  claim 1 , wherein the coating comprises chitosan, lectin, or both. 
     
     
         25 . The composition of  claim 1 , wherein the coating is a block co-polymer having a mucoadhesive block and a block that is adapted to participate in an interaction selected from affinity interactions, metal coordination, physical adsorption, host-guest interactions, and hydrogen bonding interactions. 
     
     
         26 . The composition of  claim 1 , wherein the therapeutic, diagnostic, or prophylactic agent is a biomolecule, bioactive agent, small molecule, drug, protein, vaccine, or polynucleotide. 
     
     
         27 . (canceled) 
     
     
         28 . The composition of  claim 26 , wherein the therapeutic agent is a protein. 
     
     
         29 . The composition of  claim 28 , wherein the therapeutic agent is insulin. 
     
     
         30 .- 90 . (canceled) 
     
     
         91 . The composition of  claim 14 , wherein the poly(alkylene glycol) is terminated with a carboxyl group. 
     
     
         92 . The composition of  claim 23 , wherein the polysaccharide comprises chitosan. 
     
     
         93 . The composition of  claim 23 , wherein the polypeptide comprises a lectin.