Nanoparticles for drug delivery

Abstract

The invention discloses the nanoparticles composed of chitosan, poly-glutamic acid, and at least one bioactive agent of HMG-CoA reductase inhibitors or erythropoietin. The nanoparticles are characterized with a positive surface charge and their enhanced permeability for paracellular drug delivery.

1 - 20 . (canceled) 
     
     
         21 . A pharmaceutical composition of nanoparticles for oral administration in a patient, said nanoparticles comprising a shell portion of biodegradable chitosan that is positively charged, a core portion of negatively charged substrate that is neutralized with a portion of positively charged chitosan, and erythropoietin hormone loaded within said nanoparticles. 
     
     
         22 . The pharmaceutical composition of  claim 21 , wherein said core portion comprises PGA. 
     
     
         23 . The pharmaceutical composition of  claim 22 , wherein said PGA is γ-PGA. 
     
     
         24 . The pharmaceutical composition of  claim 21 , wherein said core portion comprises heparin. 
     
     
         25 . The pharmaceutical composition of  claim 21 , wherein a surface of said nanoparticles is characterized with a positive surface charge. 
     
     
         26 . The pharmaceutical composition of  claim 21 , wherein said nanoparticles have a surface charge from about +15 mV to about +50 mV. 
     
     
         27 . The pharmaceutical composition of  claim 21 , wherein said nanoparticles are encapsulated in a softgel capsule. 
     
     
         28 . The pharmaceutical composition of  claim 27 , wherein said softgel capsule is treated with enteric coating. 
     
     
         29 . The pharmaceutical composition of  claim 21 , wherein said erythropoietin hormone is synthetic erythropoietin. 
     
     
         30 . The pharmaceutical composition of  claim 21 , wherein said erythropoietin hormone is synthetic erythropoietin produced by recombinant DNA technology. 
     
     
         31 . The pharmaceutical composition of  claim 21 , wherein said erythropoietin is characterized as a glycoprotein with a molecular mass of about 30,000 Daltons. 
     
     
         32 . The pharmaceutical composition of  claim 21 , wherein said erythropoietin hormone is a long-acting darbepoetin. 
     
     
         33 . The pharmaceutical composition of  claim 21 , wherein said erythropoietin hormone is erythropoiesis-stimulating protein. 
     
     
         34 . The pharmaceutical composition of  claim 21 , wherein said nanoparticles are formed via a simple and mild ionic-gelation method. 
     
     
         35 . A method of delivering erythropoietin hormone to blood circulation in a patient, comprising:
 providing nanoparticles according to the pharmaceutical composition of  claim 21 ;   administering said nanoparticles orally toward an intestine of the patient;   urging said nanoparticles to pass through an epithelial barrier of the intestine; and   releasing said erythropoietin hormone into the blood circulation.   
     
     
         36 . The method of  claim 35 , wherein said core portion of the nanoparticles comprises PGA. 
     
     
         37 . The method of  claim 36 , wherein said PGA is γ-PGA. 
     
     
         38 . The method of  claim 35 , wherein said core portion of the nanoparticles comprises heparin. 
     
     
         39 . The method of  claim 35 , wherein said nanoparticles are encapsulated in a softgel capsule. 
     
     
         40 . The method of  claim 39 , wherein said softgel capsule is treated with enteric coating.