Methods and products related to the intracellular delivery of polysaccharides

• US 20060083711A1
• Filed: 04/15/2005
• Published: 04/20/2006
• Est. Priority Date: 04/15/2004
• Status: Abandoned Application

• Current Assignee: Massachusetts Institute of Technology
• Original Assignee: Massachusetts Institute of Technology
• Inventors: Anderson, Daniel G., Berry, David A., Sasisekharan, Ram, Langer, Robert S., Lynn, David M.
• Application Number:
  US11/107,360
• Publication Number:
  US 20060083711A1
• Time in Patent Office: Days
• US Class Current: 424/78.120
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/726 Glycosaminoglycans, i.e. mucopolysaccharides chondroitin sulfate, dermatan sulfate A61K31/737
• CPC Class Codes: A61K 31/727 Heparin; Heparan
• CPC Class Codes: A61K 31/737 Sulfated polysaccharides, e.g. chondroitin sulfate, dermatan sulfate A61K31/727 takes precedence
• CPC Class Codes: A61K 31/785 Polymers containing nitrogen
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 47/593 Polyesters, e.g. PLGA or polylactide-co-glycolide
• CPC Class Codes: A61P 19/08 for bone diseases, e.g. rachitism, Paget's disease
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 35/00 Antineoplastic agents

Abstract

The invention relates, in part, to methods and compositions for the intracellular delivery of polysaccharides. In particular, the methods and compositions relate to the intracellular delivery of glycosaminoglycans, such as heparin. The invention in other aspects relates to the use of glycosaminoglycans for the treatment of proliferative disorders, such as cancer. The invention is still other aspects relates to improving cell viability. The invention also relates to the delivery of polysaccharides while avoiding unwanted effects of the polysaccharides. For example, heparin can be delivered while avoiding its anticoagulant effects.

Claims

1. A composition, comprising:

a cationic polymer, and

a polysaccharide, wherein the polysaccharide is present in a intracellular therapeutically effective amount.

2. The composition of claim 1, wherein the polysaccharide is a glycosaminoglycan.

3. The composition of claim 2, wherein the glycosaminoglycan is a heparin/heparin sulfate-like glycosaminoglycan.

4. The composition of claim 2, wherein the glycosaminoglycan is heparin, heparan sulfate, enoxaparin, low molecular weight heparin (LMWH) or chondroitin sulfate.

5. The composition of claim 4, wherein the chondroitin sulfate is chondroitin sulfate A or chondroitin sulfate C.

6. The composition of claim 1, wherein the therapeutically effective amount is an amount effective to promote apoptosis.

7. The composition of claim 1, wherein the therapeutically effective amount is an amount effective to treat a disease characterized by abnormal cell proliferation.

8. The composition of claim 1, wherein the cationic polymer is degradable.

9. The composition of claim 1, wherein the cationic polymer is a poly(β

-amino ester).

10. The composition of claim 9, wherein the poly(β

-amino ester) is A5, A8, A11, B6, B9, B11, B14, C4, C12, C32, D6, D94, E7, E14, E28, F20, F28, G5, C32-2, U28, U28-3, JJ28-3, D94-5, E28-3, U32, U32-2, JJ28, JJ32, JJ32-3, F28-6, F32 or F32-2.

11-31. -31. (canceled)

32. A composition, comprising:

a polysaccharide,

a cationic polymer, and

a pharmaceutically acceptable carrier, wherein more cationic polymer is present in the composition (w/w) than the polysaccharide.

33-41. -41. (canceled)

42. A composition, comprising:

a poly(β

-amino ester), and

a polysaccharide.

101. A method for the intracellular delivery of a polysaccharide, comprising:

administering the composition of claim 42.

43-50. -50. (canceled)

51. A composition, comprising:

a cationic polymer,

a polysaccharide, and

a targeting molecule.

52-59. -59. (canceled)

60. A method for the intracellular delivery of a therapeutically effective amount of a polysaccharide, comprising:

administering the polysaccharide complexed to a cationic polymer to promote the uptake of the polysaccharide into a cell in a therapeutically effective amount.

61-77. -77. (canceled)

78. A method for promoting apoptosis in a subject, comprising:

administering a glycosaminoglycan intracellularly in an amount effective to promote apoptosis, wherein the glycosaminoglycan is delivered in an intracellular therapeutically effective amount to promote apoptosis.

79-87. -87. (canceled)

88. A method for treating a disease characterized by abnormal cell proliferation in a subject, comprising:

administering a glycosaminoglycan intracellularly in an amount effective to treat the disease, wherein the glycosaminoglycan is delivered in an intracellular therapeutically effective amount to treat the disease.

89-100. -100. (canceled)

102. (canceled)

103. A method for the intracellular delivery of a polysaccharide, comprising:

administering the polysaccharide complexed to a cationic polymer to a non-macrophage cell, wherein the polysaccharide is not present in excess of the cationic polymer.

104. A method of promoting cell viability, comprising:

contacting a cell with a cationic polymer-polysaccharide conjugate prior to freezing the cell in an amount effective to increase the cell'"'"'s viability when thawed.

105-106. -106. (canceled)

107. A method for inhibiting abnormal cell proliferation, comprising:

administering a glycosaminoglycan complexed to a cationic polymer in an amount effective to inhibit cell proliferation.

108-120. -120. (canceled)