Nanoparticles for drug delivery
View Patent ↗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. 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 that consists of positively charged chitosan and one negatively charged substrate, wherein said negatively charged substrate is neutralized with a portion of said positively charged chitosan in the core portion, and a HMG-CoA reductase inhibitor loaded within said nanoparticles.
2. The pharmaceutical composition of claim 1 , wherein said negatively charged substrate in the core portion is poly(glutamic) acid (PGA).
3. The pharmaceutical composition of claim 2 , wherein said PGA is γ-PGA, α-PGA, derivatives or salts of PGA.
4. The pharmaceutical composition of claim 1 , wherein said negatively charged substrate in the core portion is heparin or glycosaminoglycan.
5. The pharmaceutical composition of claim 1 , wherein a surface of said nanoparticles is characterized with a positive surface charge.
6. The pharmaceutical composition of claim 1 , wherein said nanoparticles have a surface charge from about +15 mV to about +50 mV.
7. The pharmaceutical composition of claim 1 , wherein said nanoparticles are loaded in a capsule or tablet.
8. The pharmaceutical composition of claim 7 , wherein said capsule or tablet is treated with an enteric coating.
9. The pharmaceutical composition of claim 1 , wherein said HMG-CoA reductase inhibitor is a statin.
10. The pharmaceutical composition of claim 1 , wherein said HMG-CoA reductase inhibitor is a statin selected from the group consisting of lovastatin, simvastatin, pravastatin, fluvastatin, cerivastatin, atovastatin, rosuvastatin, pitavastatin, and combinations thereof.
11. The pharmaceutical composition of claim 1 , wherein said HMG-CoA reductase inhibitor is bisphosphonates.
12. The pharmaceutical composition of claim 1 , wherein said nanoparticles are formed via a simple and mild ionic-gelation method.
13. A method of delivering an HMG-CoA reductase inhibitor to blood circulation in a patient, comprising:
providing nanoparticles according to the pharmaceutical composition of claim 1 ;
administering said nanoparticles orally toward an intestine of the patient;
passing said nanoparticles through an epithelial barrier of the intestine; and
releasing said HMG-CoA reductase inhibitor into the blood circulation.
14. The pharmaceutical composition of claim 7 , wherein at least one absorption enhancer is co-encapsulated with said nanoparticles in the capsule.
15. The pharmaceutical composition of claim 7 , wherein the capsule further comprises a second nanoparticle that contains at least one absorption enhancer.
16. The pharmaceutical composition of claim 9 , wherein the statin is somatostatin or synthetic analogues, modifications and pharmacologically active fragments thereof.