Nanoparticles for protein drug delivery

1. A pharmaceutical composition for treating a subject comprising two or more bioactive nanoparticles, thus treating the subject by co-administering said two or more bioactive nanoparticles to said subject, wherein a first bioactive nanoparticle comprises a shell portion that is dominated by a first positively charged chitosan, a core portion that consists of a first negatively charged substrate, the first positively charged chitosan, and at least a zero-charge first compound, and wherein a second bioactive nanoparticle comprises a shell portion that is dominated by a second positively charged chitosan, a core portion that contains a second negatively charged substrate, the second positively charged chitosan, and at least a second compound.

2. The pharmaceutical composition of claim 1 , wherein the first and second nanoparticles are loaded in capsules.

3. The pharmaceutical composition of claim 2 , wherein said capsules are treated with an enteric coating.

4. The pharmaceutical composition of claim 2 , wherein said capsules further comprise at least a solubilizer or pharmacopoeial excipients.

5. The pharmaceutical composition of claim 2 , wherein said capsules further comprise a permeation enhancer.

6. The pharmaceutical composition of claim 5 , wherein said permeation enhancer is selected from the group consisting of Ca 2+ chelators, bile salts, anionic surfactants, medium-chain fatty acids, phosphate esters, chitosan, and chitosan derivatives.

7. The pharmaceutical composition of claim 1 , wherein the first nanoparticle is loaded in a first capsule and the second nanoparticle is loaded in a second capsule for co-administration to said subject.

8. The pharmaceutical composition of claim 7 , wherein said first capsule or said second capsule is treated with an enteric coating.

9. The pharmaceutical composition of claim 7 , wherein said first capsule or said second capsule further comprises at least a solubilizer or pharmacopoeial excipients.

10. The pharmaceutical composition of claim 7 , wherein said first capsule or said second capsule further comprises a permeation enhancer.

11. The pharmaceutical composition of claim 10 , wherein said permeation enhancer is selected from the group consisting of Ca 2+ chelators, bile salts, anionic surfactants, medium-chain fatty acids, phosphate esters, chitosan, and chitosan derivatives.

12. The pharmaceutical composition of claim 1 , wherein the first or second chitosan comprises N-trimethyl chitosan, EDTA-chitosan, or chitosan derivatives.

13. The pharmaceutical composition of claim 1 , wherein said first and second nanoparticles are loaded in tablets or pills.

14. The pharmaceutical composition of claim 1 , wherein said first and second nanoparticles are freeze-dried, thereby said nanoparticles being in a powder form.

15. The pharmaceutical composition of claim 1 , wherein said second compound further comprises magnesium sulfate or TPP.

16. The pharmaceutical composition of claim 1 , wherein the second compound comprises at least one non-insulin anti-diabetic drug.

17. The pharmaceutical composition of claim 16 , wherein said non-insulin anti-diabetic drug is selected from the group consisting of insulin sensitizers, insulin secretagogues, GLP-1 analogs, and DPP-4 inhibitors.

18. The pharmaceutical composition of claim 16 , wherein said non-insulin anti-diabetic drug comprises liraglutide, exenatide, albiglutide, or taspoglutide.

19. The pharmaceutical composition of claim 16 , wherein said non-insulin anti-diabetic drug is selected from the group consisting of alpha-glucosidase inhibitors, amylin analog, sodium-glucose co-transporter type 2 (SGLT2) inhibitors, benfluorex, and tolrestat.

20. The pharmaceutical composition of claim 1 , wherein the first or second compound is insulin or an insulin analog.