PEGYLATED LIPOSOMAL FORMULATIONS FOR PHOTODYNAMIC TREATMENT OF INFLAMMATORY DISEASES

• US 20110160642A1
• Filed: 11/14/2008
• Published: 06/30/2011
• Est. Priority Date: 11/15/2007
• Status: Abandoned Application

• Current Assignee: Biolitec Unternehmensbeteiligungs II AG
• Original Assignee: Biolitec Unternehmensbeteiligungs II AG
• Inventors: Albrecht, Volker, Neuberger, Wolfgang
• Application Number:
  US12/742,336
• Publication Number:
  US 20110160642A1
• Time in Patent Office: Days
• US Class Current: 604/21
• CPC Class Codes: A61K 41/0071 PDT with porphyrins having exactly 20 ring atoms, i.e. based on the non-expanded tetrapyrrolic ring system, e.g. bacteriochlorin, chlorin-e6, or phthalocyanines
• CPC Class Codes: A61K 47/6911 the form being a liposome
• CPC Class Codes: A61K 9/1271 Non-conventional liposomes, e.g. PEGylated liposomes, liposomes coated with polymers liposome as conjugate A61K47/6911
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]

Abstract

A PDT treatment system designed to treat all types of human inflammatory disorders. A suitable drug delivery system is developed to target proliferating cells, at inflamed sites, populated with macrophages and other inflammatory mediators. The hydrophobic photosensitizer is loaded into the liposomal bilayer formed of synthetic phospholipids; at least one of the synthetic phospholipids is conjugated to polyethylene glycol (PEG) molecules, to prevent accumulation in the liver and spleen. Further, (PEG) formulated photosensitizer increases the circulatory half-life of the drug, enhances solubility, and modifies pharmacokinetic and pharmacodynamic properties. The formulation, thus, leads to a higher amount of delivered drug to the diseased target synovial tissue, increasing clinical effectiveness. In one embodiment, pegylated liposomes loaded with mTHPC are administered to diseased synovial joints, followed by light irradiation. Activated photosensitizer induces cytotoxic effect in the diseased synovial cells, thus preventing further inflammation and joint erosion and minimizing joint damage.

Claims

1. A pegylated liposomal photosensitizer formulation for use in reducing inflammation comprising:

a liposomal bilayer, wherein the said bilayer consists of synthetic phospholipids;

at least one synthetic phospholipids is a polyethylene glycol (PEG) linked phospholipid; and

a hydrophobic photosensitizer, contained within said liposomal bilayer.

2. The pegylated liposomal photosensitizer formulation according to claim 1, including a medicament carrier.

3. The pegylated liposomal photosensitizer formulation according to claim 1, wherein said synthetic phospholipids are dipalmitoyl phosphatidyl choline, dipalmitoyl phosphatidyl glycerol and pegylated distearoyl phosphatidyl ethanolamine.

4. The pegylated liposomal photosensitizer formulation according to claim 1, wherein said hydrophobic photosensitizer is selected from the group consisting of dihydro- and tetrahydro-porphyrins.

5. The pegylated liposomal photosensitizer formulation according to claim 4, wherein said hydrophobic photosensitizer is temoporfin

6. The pegylated liposomal photosensitizer formulation according to claim 1, wherein the concentration of the photosensitizer is from 0.0001 to 0.15 percent w/v.

7. The pegylated liposomal photosensitizer formulation according to claim 1 wherein said polyethylene glycols have molecular weights up to about 40,000 to 50,000 Da.

8. The pegylated liposomal photosensitizer formulation according to claim 1 wherein said formulation avoids early sequestration of said pegylated photosensitizer by a liver of said animal and avoids detection by cells of its mononuclear phagocyte system.

9. The method for treating inflamed tissue in an animal comprising the steps of:

administering an effective amount of a pegylated liposomal photosensitizer formulation according to claim 1 to said inflamed tissue;

allowing sufficient time for uptake of said conjugated complex by said inflamed tissue;

allowing sufficient time for said inflamed tissue to interact with said conjugated complex; and

applying sufficient amount of radiation to said inflamed tissue to rein said inflammation.

10. The method for treating inflamed tissue according to claim 9 wherein said animal cells are selected from the group consisting of a mononuclear phagocyte system, a phagocytic tissue cell, and a macrophage cell.

11. The method for treating inflamed tissue according to claim 9 wherein said animal cell is in a mononuclear phagocyte system of said animal.

12. The method for treating inflamed tissue according to claim 9 wherein said animal cell is a phagocytic tissue cell.

13. The method for treating inflamed tissue according to claim 9 wherein said animal cell is a macrophage cell.

14. The method for treating inflamed tissue according to claim 9 wherein tissue inflammation is caused in animal joints by autoimmune diseases or arthritic problems.

15. The method for treating inflamed tissue according to claim 9 wherein said administering step is selected from the group consisting of local injection, topical application and systemic application into said inflamed tissue.

16. The method for treating inflamed tissue according to claim 9 wherein said activated compound targets hyperplastic synovial tissue

17. The method for treating inflamed tissue according to claim 16 wherein said hyperplastic synovial tissue is composed of pannus cells.