Drug delivery systems for photodynamic therapy

• US 6,693,093 B2
• Filed: 05/08/2001
• Issued: 02/17/2004
• 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.
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): FUBARA, BLESSING M
• Application Number:
  US09/851,641
• Publication Number:
  US 20020155089A1
• Time in Patent Office: 1,015 Days
• Field of Search: 514/185, 514/8, 514/21, 514/453, 514/455, 514/410, 514/58, 514/561, 604/20, 604/522, 424/9.6, 424/85.1, 424/613, 424/9.36, 424/450, 424/9.45, 424/183.1, 424/176.1
• US Class Current: 514/185
• 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 method for formulating a photosensitizer carrier composition comprising

combining one or more photosensitizer and one or more block copolymer in solution and

drying said photosensitizer and copolymer combination,

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

2. The method of claim 1 further comprising a step of hydrating said photosensitizer and copolymer combination to form a complex.

3. The method of claim 1, wherein said block copolymer comprises polyoxyethylene and polyoxypropylene;

polytetrahydrofuran;

or polyaspartic acid.

4. The method of claim 3, 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).

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

6. The method of claim 5, wherein said derivative of porphyrin is selected from the group consisting of green porphyrins, tetrahydrochlorins, pyrophenophorphides, purpurins, texaphyrins, phenothiaziniums, phthalocyanines, napthalocyanines, porphycenes and pheophorbides.

7. The method of claim 6, wherein said tetrahydrochlorins are selected from the group consisting of chlorins, hydroxychlorins, bacteriochlorins, and isobacteriochlorins.

8. The method of claim 7, wherein said green porphyrin is a benzoporphyrin derivative (BPD).

9. The method of claim 8, wherein said BPD is selected from the group consisting of benzoporphyrin derivative monoacid ring A (BPD-MA), benzoporphyrin derivative monoacid ring B (BPD-MB), A-EA6, B-EA6, A-B3 and B-B3.

10. The method of claim 2, wherein said step of combining one or more photosensitizer and one or more block copolymer in solution further comprises a hydratable solid support on which said photosensitizer and block copolymer combination may deposit.

11. The method of claim 10, wherein said solid support is not capable of dissolving in said copolymer in solution.

12. The method of claim 10, wherein said solid support is capable of dissolving in said optional hydrating step.

13. A method for conducting photodynamic therapy comprising:

(a) administering a photosensitizer and copolymer complex produced by the method of claim 2 to a subject in need of photodynamic therapy; and

(b) irradiating said subject to activate said photosensitizer.