Artificial cell constructs for cellular manipulation
The present invention contemplates induction of immunological tolerance thereby providing permanent allograft acceptance. This method obviates the need for a lifelong regimen of immunosuppressive agents which can increase the risk of infection, autoimmunity, and cancer. Immunological tolerance is thought to be mediated by regulatory T lymphocytes (T reg cells) with immunosuppressive capabilities. A therapeutically relevant platform comprising artificial constructs are contemplated comprising numerous soluble and surface bound T reg cell stimulating factors that may induce tolerance following allograft transplantation. Such artificial constructs, being the size of a cell, have surface bound monoclonal antibodies specific to regulatory T-cell surface moieties and encapsulated soluble regulatory T-cell modulating factors.
1. A synthetic microparticle comprising at least one polymer and an internal structure, said internal structure comprising a plurality of compartments, wherein a soluble CCL22 chemokine is encapsulated within said plurality of compartments.
2. The synthetic microparticle of claim 1 , wherein said microparticle is biodegradable.
3. The synthetic microparticle of claim 2 , wherein said biodegradable microparticle undergoes a controlled chemokine release.
4. The synthetic microparticle of claim 3 , wherein said controlled chemokine release is a short term release comprising between ten-twenty four hours.
5. The synthetic microparticle of claim 3 , wherein said controlled chemokine release is a long term release comprising between twenty four hours and one year.
6. The synthetic microparticle of claim 3 , wherein said controlled chemokine release is maintained for at least twenty days.
7. The synthetic microparticle of claim 1 , wherein said at least one polymer comprises a polylactide-co-glycolide polymer.
8. The synthetic microparticle of claim 1 , wherein said at least one polymer comprises a lactic acid monomer.
9. The synthetic microparticle of claim 8 , wherein said at least one polymer further comprises a glycolic acid monomer.
10. The synthetic microparticle of claim 9 , wherein said at least one polymer comprises said lactic acid monomer and said glycolic acid monomer in a predetermined ratio.
11. The synthetic microparticle of claim 10 , wherein said predetermined ratio is 50:50.
12. The synthetic microparticle of claim 10 , wherein said predetermined ratio is determined by a mathematical model.
13. The synthetic microparticle of claim 1 , wherein the molecular weight of said at least one polymer is selected from the group consisting of approximately 10 kDa, a range of approximately 18-30 kDa and a range of approximately 40-78 kDa.
14. The synthetic microparticle of claim 1 , wherein the average molecular weight of said at least one polymer is approximately 15 kilodaltons.
15. The synthetic microparticle of claim 1 , wherein said microparticle is approximately ten to twenty microns in diameter.
16. The synthetic microparticle of claim 1 , wherein said compartments range between approximately 300-500 nanometers in diameter.
17. The synthetic microparticle of claim 1 , further comprising a pharmaceutical formulation.