Calciumphosphate-based nanoparticles as carrier-systems for photodynamic therapy

摘要

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.

主权项

1. A nanoparticle pharmaceutical formulation for photodynamic therapy comprising:
a crystalline or amorphous biodegradable ceramic core with a diameter in the range of 5-1000 nm; a therapeutically effective amount of a hydrophobic or hydrophilic photosensitizer; and a stabilizing agent; suitable for intravenous administration and having improved solubility in physiological solutions; wherein said ceramic core is solid or hollow and the material of said core is selected from the group consisting of calcium phosphate and calcium carbonate; wherein said hydrophobic or hydrophilic photosensitizer is selected from the group consisting of tetrapyrrole derivatives, phenazinium dyes, phenothiazinium dyes, and xanthene dyes; and wherein said stabilizing agent is selected from the group consisting of cationic, non-ionic and anionic polymers.