Nanoparticles for protein drug delivery

1. A pharmaceutical composition of nanoparticles characterized by enhancing intestinal paracellular transport, each nanoparticle comprising a first component of at least one bioactive agent, a second component of low molecular weight chitosan, and a third component that is negatively charged, wherein said second component dominates on a surface of said nanoparticle.

2. The pharmaceutical composition of claim 1 , wherein said third component is γ-PGA.

3. The pharmaceutical composition of claim 2 , wherein the first component comprises insulin at a concentration range of 0.075 to 0.091 mg/ml, the second component at a concentration range of 0.67 to 0.83 mg/ml, and the third component at a concentration range of 0.150 to 0.184 mg/ml.

4. The pharmaceutical composition of claim 1 , wherein said third component is alginate.

5. The pharmaceutical composition of claim 1 , wherein the at least one bioactive agent is an antagonist for Alzheimer's disease.

6. The pharmaceutical composition of claim 1 , wherein the at least one bioactive agent is memantine hydrochloride.

7. The pharmaceutical composition of claim 1 , wherein the at least one bioactive agent is insulin or insulin analog.

8. The pharmaceutical composition of claim 1 , wherein the at least one bioactive agent is a peptide.

9. The pharmaceutical composition of claim 1 , wherein said nanoparticles are further encapsulated in a gelcap.

10. The pharmaceutical composition of claim 1 , wherein said second component is crosslinked.

11. The pharmaceutical composition of claim 10 , wherein the second component is crosslinked at a degree of crosslinking less than 50%.

12. The pharmaceutical composition of claim 10 , wherein the second component is crosslinked at a degree of crosslinking ranged between 1% and 20%.

13. The pharmaceutical composition of claim 10 , wherein the second component is crosslinked with a crosslinking agent selected from a group consisting of genipin, its derivatives, analogs, stereoisomers and mixtures thereof.

14. The pharmaceutical composition of claim 10 , wherein the second component is crosslinked with epoxy compounds.

15. The pharmaceutical composition of claim 1 , wherein the low molecular weight chitosan has a molecular weight of 80 kDa or less.

16. The pharmaceutical composition of claim 1 , wherein the low molecular weight chitosan is further grafted with a polymer having a chemical formula as:

where R is ≧12.

17. The pharmaceutical composition of claim 1 , wherein a surface of the nanoparticles is characterized with a positive surface charge.

18. The pharmaceutical composition of claim 1 , wherein the at least one bioactive agent is heparin.