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AssigneesUniversitäT Duisburg-Essen, biolitec, Inc.
InventorsBurkhatd Gitter, Susanna Grafe, Arno Wiehe, Volker Albrecht, Matthias Epple, Janine Schwiertz, Kathirvel Ganesan
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The present invention provides pharmaceutical photosensitizer-loaded nanoparticle formulations and their methods of preparation for photodynamic therapy, comprising a hydrophobic or hydrophilic photosensitizer, nanoparticulate calcium phosphate and in certain cases auxiliary reagents such as stabilizers. The calcium phosphate-based nanoparticle formulations of the present invention provide excellent storage stability and therapeutically effective amounts of photosensitizer for intravenous or topical administration. In a preferred embodiment, tetrapyrrole derivatives such as porphyrins, chlorins and bacteriochlorins, are the preferred hydrophobic photosensitizers to be formulated in calcium phosphate nanoparticle formulations for photodynamic tumor therapy. Additionally, 5,10,15,20-tetrakis(4-phosphonooxyphenyl)porphine (pTPPP) is a preferred hydrophilic photosensitizer for photodynamic tumor therapy. In another preferred embodiment, hydrophilic cationic and anionic photosensitizers, especially those of the phenazinium, phenothiazinium and xanthenes series have been found to inactive pathogen bacteria and are the preferred photosensitizers to be formulated in calcium phosphate nanoparticle formulations for antibacterial photodynamic therapy. In another embodiment, photosensitizing nanoparticle formulations are useful to locate cells, tissues or bacteria by using fluorescence imaging methods.
1-12. (canceled)
A nanoparticle pharmaceutical formulation for photodynamic therapy comprising:
The nanoparticle pharmaceutical formulation according to claim 133, further comprising a stabilizing agent selected from the group of cationic, non-ionic and anionic polymers.
The nanoparticle pharmaceutical formulation according to claim 134, wherein said anionic stabilizing agent are selected from the group consisting of sodium polystyrene sulfonate (PSS) and carboxymethylcellulose (CMC).
The nanoparticle pharmaceutical formulation according to claim 134, wherein said cationic stabilizing agent are selected from the group consisting of poly(allylamine) hydrochloride (PAH) and polyethylene imine (PEI).
The nanoparticle pharmaceutical formulation according to claim 134, wherein said photosensitizer is selected from the group consisting of porphyrins, chlorins, bacteriochlorins, methylene blue, toluidine blue, safranin, and erythrosine.
The nanoparticle pharmaceutical formulation according to claim 133, wherein said biodegradable ceramic core has a diameter in the range of 50-250 nm.
The nanoparticle pharmaceutical formulation according to claim 133, wherein the Ca2+ ion of said calcium phosphate or calcium carbonate is substituted in part up to a hilly extent by a ion selected from the group consisting of Mg2+ ion, for Al3+ ion, or Sr2+ ion.
The nanoparticle pharmaceutical formulation according to claim 133, wherein said nanoparticles are equipped with a targeting ligand selected from the group consisting of an antibody, an antibody fragment, a RGD peptide, and combinations of these.
A method of preparation of nanoparticle pharmaceutical formulations comprising the steps of,
Dependencies are inferred from the claim text.