ERYTHROCYTE-BASED DELIVERY SYSTEM, METHOD OF PREPARATION AND USES THEREOF

• US 20110262415A1
• Filed: 12/18/2009
• Published: 10/27/2011
• Est. Priority Date: 12/21/2008
• Status: Abandoned Application

• Current Assignee: Consiglio Nazionale Delle Ricerche (Repubblica Italiana)
• Original Assignee: Consiglio Nazionale Delle Ricerche (Repubblica Italiana)
• Inventors: Lisi, Antonella, Grimaldi, Settimio, Cinti, Caterina
• Application Number:
  US13/132,008
• Publication Number:
  US 20110262415A1
• Time in Patent Office: Days
• US Class Current: 424/93.73
• CPC Class Codes: A61K 41/0028 Disruption, e.g. by heat or ultrasounds, sonophysical or sonochemical activation, e.g. thermosensitive or heat-sensitive liposomes, disruption of calculi with a medicinal preparation and ultrasounds
• CPC Class Codes: A61K 47/6901 Conjugates being cells, cell fragments, viruses, ghosts, red blood cells or viral vectors
• CPC Class Codes: C12N 5/0641 Erythrocytes

Abstract

The invention relates to a cell-based drug delivery system comprising magneto nanoparticles, erythrocytes and a fusion-protein, its preparation and uses thereof in particular as a delivery system for biologically active compounds.

Claims

1. A compound delivery system to a target cell comprising:

an haemoglobin-deprived erythrocyte,

a magnetic or super-paramagnetic nano-particle located inside the erythrocyte and

a protein located on the membrane of the erythrocyte able to induce the fusion of the membrane of said erythrocyte to the membrane of the target cell.

2. The system according to claim 1 wherein the magnetic or super-paramagnetic nano-particle is of γ

Fe₂O₃.

3. The system according to claim 1 wherein the magnetic or super-magnetic nano-particle has a diameter between 5 to 100 nm.

4. The system according to claim 1 wherein the magnetic or super-magnetic nano-particle is covered by a surfactant.

5. The system according to claim 1 wherein the magnetic or super-magnetic nano-particle is further modified to comprise an additional agent.

6. The system according to claim 5 wherein the additional agent is selected from the group consisting of an amino or carboxy or esterified group covalently bound to a fluorescent or non-fluorescent functional group.

7. The system of claim 1 wherein the protein is a virosome-derived protein.

8. The system according to claim 7 wherein the virosome is from an influenza virus virosome or a vesicular stomatitis virus virosome or an Epstein Barr virus virosome.

9. The system according to claim 1 being loaded with a pharmacological or biological therapeutic compound.

10. The system according to claim 9 wherein the pharmacological or biological therapeutic compound is selected from the group consisting of:

antiretroviral compound, small molecule, pro-drug, phosphorylated pro-drug or a chemiotherapeutic compound.

13. A method for the preparation of the system of claim 1, comprising:

a) depriving isolated erythrocyte of haemoglobin;

b) incubating under appropriated conditions the haemoglobin-deprived erythrocyte with a protein able to induce the fusion of the membrane of said erythrocyte to the membrane of a target cell, thus obtaining an erythrocyte-protein complex;

c) purifying said complex; and

d) incubating the purified complex with magnetic or super-paramagnetic nano-particles under appropriate conditions.

14. A pharmaceutical composition comprising the system of claim 1 and pharmaceutically acceptable diluents, carrier and/or excipients.

11-12. -12. (canceled)