Targeted delivery of antiviral compounds through hemoglobin bioconjugates
This invention relates to targeted delivery of anti-viral compounds through protein bioconjugation. More particularly, it relates to an anti-viral compound conjugated to a protein, such as hemoglobin and to a method of treating a viral infection using said conjugate. The invention also provides a method of targeted drug delivery of an anti-viral nucleoside analogue to macrophages, cells comprising a hemoglobin receptor and to CD163 bearing cells.
1 A pharmaceutical composition comprising an anti-viral nucleoside analogue and a pharmaceutically acceptable carrier, wherein said carrier is hemoglobin.
2 . The pharmaceutical composition of claim 1 wherein the hemoglobin is conjugated to the anti-viral nucleoside analogue to form a hemoglobin-anti-viral nucleoside conjugate.
3 . The pharmaceutical composition of claim 2 wherein the conjugate is a hemoglobin-phosphoramidate-anti-viral nucleoside analogue conjugate.
4 . The pharmaceutical composition of claim 2 wherein the conjugate is labeled.
5 . The pharmaceutical composition of claim 4 wherein the conjugate is fluorescently- or radio-labeled.
6 . The pharmaceutical composition of claim 2 , wherein the conjugate is capable of binding haptoglobin.
7 . The pharmaceutical composition of claim 6 , wherein the conjugate is further bound to haptoglobin to form a haptoglobin-hemoglobin-anti-viral nucleoside analogue complex.
8 . The pharmaceutical composition of claim 2 wherein the anti-viral nucleoside analogue is selected from the group consisting of AraA, AraC, and ribavirin.
9 . The pharmaceutical composition of claim 8 , wherein the anti-viral nucleoside analogue is ribavirin.
10 . The pharmaceutical composition of claim 1 wherein the hemoglobin directs delivery of the anti-viral nucleoside compound to a CD163 bearing cell or a cell comprising a receptor for hemoglobin or its derivatives.
11 . The pharmaceutical composition of claim 10 wherein the cell is a macrophage.
12 . The pharmaceutical composition of claim 1 , wherein the hemoglobin is non-intramolecularly cross-linked.
13 . The pharmaceutical composition of claim 1 wherein the hemoglobin is human hemoglobin.
14 . A method of treating a viral infection comprising administering to a subject in need thereof, a pharmaceutical composition of claim 1 .
15 . The method of claim 14 , wherein the anti-viral nucleoside analogue is ribavirin.
16 . The method of claim 15 , wherein the viral infection is selected from the group consisting of Hepatitis C, HIV, SARS, coronavirus, and RSV.
17 . The method of claim 14 , wherein the pharmaceutical composition is administered intravenously.
18 . A method of treating a viral or non-viral condition that is modulated through macrophages, comprising administering to a patient in need thereof, a pharmaceutical composition of claim 1 .
19 . A method of reducing the incidence of hemolytic anemia associated with anti-viral nucleoside therapy comprising administration of an effective amount the pharmaceutical composition of claim 2 .
20 . The method of treating a viral infection in accordance with claim 14 comprising administering the pharmaceutical composition in combination with IFN or PEG-IFN
21 . The method of claim 20 , wherein the viral infection is hepatitis C.
22 . A method of treating a non-viral infection comprising administering to patient in need thereof, a pharmaceutical composition of claim 1.