Drug delivery systems for photodynamic therapy

• US 20020155089A1
• Filed: 05/08/2001
• Published: 10/24/2002
• Est. Priority Date: 05/08/2000
• Status: Active Grant

• Current Assignee: University of British Columbia
• Original Assignee: University of British Columbia
• Inventors: Dolphin, David, Chowdhary, Rubinah K.
• Granted Patent: US 6,693,093 B2
• Time in Patent Office: Days
• US Class Current: 424/78.17
• CPC Class Codes: A61K 31/409 having four such rings, e.g. porphine derivatives, bilirubin, biliverdine hemin, hematin A61K31/555
• CPC Class Codes: A61K 31/555 containing heavy metals, e.g. hemin, hematin, melarsoprol
• CPC Class Codes: A61K 31/787 containing heterocyclic rings having nitrogen as a ring hetero atom
• CPC Class Codes: A61K 41/00 Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
• CPC Class Codes: A61K 41/0057 Photodynamic therapy with a photosensitizer, i.e. agent able to produce reactive oxygen species upon exposure to light or radiation, e.g. UV or visible light; photocleavage of nucleic acids with an agent
• 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 9/0009 involving or responsive to electricity, magnetism or acoustic waves; Galenical aspects of sonophoresis, iontophoresis, electroporation or electroosmosis microelectromechanical systems A61K9/0097
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61K 9/10 Dispersions; Emulsions A61K9/06 takes precedence; composition of dispersions, emulsions A61K47/00
• CPC Class Codes: A61K 9/1278 Post-loading, e.g. by ion or pH gradient
• CPC Class Codes: A61P 35/00 Antineoplastic agents

Abstract

The invention is generally related to the field of photodynamic therapy by use of photosensitizers and stabilized formulations of the photosensitizers. These formulations may be used to deliver a photosensitizer as a pharmaceutical, agricultural, or industrial agent. The photosensitizer containing formulations and compositions of the invention comprise one or more block copolymers. Furthermore, the invention relates to processes for the production of, and application of, said formulations and compositions as photosensitizer drug delivery systems.

Claims

1. A photosensitizer carrier composition comprising

(a) one or more photosensitizer and

(b) one or more block copolymer in liquid form capable of forming a complex with said photosensitizer and wherein said copolymer is i) not an amphiphilic polymer of polystyrene sodium sulphonate and vinyl naphthalene, and ii) not poloxamer 188.

2. A method for formulating a photosensitizer carrier composition of claim 1 comprising combining one or more photosensitizer and one or more block copolymer in solution, wherein said copolymer is i) not an amphiphilic polymer of polystyrene sodium sulphonate and vinyl naphthalene, and ii) not poloxamer 188.

3. The method of claim 2 further comprising the step of optionally drying said photosensitizer and copolymer combination.

4. A method for formulating a photosensitizer carrier composition according to claim 1 comprising combining one or more photosensitizer and one or more block copolymer wherein said copolymer is in a liquefied state, said photosensitizer is soluble in said copolymer, and said copolymer is i) not an amphiphilic polymer of polystyrene sodium sulphonate and vinyl naphthalene, and ii) not poloxamer 188.

5. The method of claim 3 further comprising the step of optionally hydrating said photosensitizer and copolymer combination to form a complex.

6. A method for conducting photodynamic therapy comprising:

(a) administering a photosensitizer and copolymer complex produced by hydration of the composition of claim 1 to a subject in need of photodynamic therapy; and

(b) irradiating said subject to activate said photosensitizer;

wherein said copolymer is i) not an amphiphilic polymer of polystyrene sodium sulphonate and vinyl naphthalene, and ii) not poloxamer 188.

7. The composition of claim 1, wherein said complex is selected from the group consisting of micelles, emulsions, gels, matrix or transition phases between the preceding defined states.

8. The composition of claim 1, wherein said block copolymer comprises polyoxyethylene and polyoxypropylene;

polytetrahydrofuran;

or polyaspartic acid.

9. The composition of claim 8, wherein said polyoxyethylene-polyoxypropylene block copolymer is selected from the group consisting of poloxamer 403 (P123), poloxamer 407 (F127), poloxamer 402 (L122), poloxamer 181 (L61), poloxamer 401 (L121), poloxamer 185 (P65), and poloxamer 338 (F108).

10. The composition of claim 1, wherein said photosensitizer is selected from the group consisting of porphyrins, pyrroles, tetrapyrrolic compounds, expanded pyrrolic macrocycles and their derivatives.

11. The composition of claim 10, wherein said porphyrin derivative is selected from the group consisting of green porphyrins, tetrahydrochlorins, pyrophenophorphides, purpurins, texaphyrins, phenothiaziniums, phthalocyanines, napthalocyanines, porphycenes and pheophorbides.

12. The composition of claim 11, wherein said tetrahydrochlorins are selected from the group consisting of chlorins, hydroxychlorins, bacteriochlorins, and isobacteriochlorins.

13. The composition of claim 12, wherein said green porphyrin is selected a benzoporphyrin derivative (BPD).

14. The composition of claim 13, wherein said BPD is selected from the group consisting of BPD-MA, BPD-MB, A-EA6, B-EA6, A-B3 and B-B3.

15. The method of claim 5 wherein said combining step further comprises a hydratable solid support on which said photosensitizer and block copolymer combination may deposit.

16. The method of claim 15, wherein said solid support is not capable of dissolving in said liquefied copolymer.

17. The method of claim 15, wherein said solid support is capable of dissolving in said optional hydrating step.

19. The composition of claim 18 wherein said agent is not a fluorocarbon.

20. A method for conducting photodynamic therapy comprising administering a photosensitizer and copolymer complex produced by hydration of the composition of claim 18 to a subject in need of photodynamic therapy, and irradiating said subject to activate said photosensitizer.

18. A photosensitizer carrier composition comprising a photosensitizer, poloxamer 188 (F68) and an emulsion forming agent, wherein said agent is not a fluorocarbon selected from the group consisting of FC43, PP11, and PP25.