Biolitec Pharma Marketing Ltd

Ceramoptec Industries, Inc.

Biolitec Unternehmensbeteilligungs Ll Ag

Alfred Fahr

Wolfgang Neuberger

Susanna Gräfe

Dietrich Scheglmann

Volker Albrecht

Arno Wiehe

Nikolay Nifantiev

Gerhard Wieland

Albrecht Volker

Pharmaceutical pegylated liposomal formulations for photodynamic therapy are presented. The pegylated liposomal formulation provides therapeutically effective amounts of the photosensitizer for intravenous administration. At least one of the phospholipids in the liposomes has been linked with poly ethylene glycol (PEG) as an integral part of the phospholipids. The formed pegylated liposomes contain the hydrophobic photosensitizer within the lipid bilayer membrane. Pegylation of liposomes carrying the hydrophobic photosensitizer helps to maintain the drug level within the therapeutic window for longer time periods and provides the drug a longer circulating half life in vivo. Further the pegylated formulation of hydrophobic photosensitizers shows improved pharmacokinetics over standard non-liposomal formulations thus enhancing the efficacy of PDT with the pegylated liposomal formulations.

Pegylated liposomal formulations of hydrophobic photosensitizers for photodynamic therapy

Oral formulations and method of formulating photosensitive agents for oral administration during photodynamic therapy (PDT) and Antimicrobial photodynamic therapy (APDT) treatment are presented. The oral formulated photosensitizers show increased solubility and permeability, thus improving the bioavailability of photosensitizers at the treatment site. An orally administered photosensitizer is suitably formulated for mucosal adhesion and absorption via gastrointestinal mucosal membranes. Oral formulation provided herein use lipids and known proteins as carriers for photosensitizers by oral route. Carriers for encapsulating preselected photosensitizers include conventional liposomes, pegylated liposomes, nanoemulsions, nanocrystrals, nanoparticles, fatty emulsions, lipidic formulations, hydrosols, SMEDDS, Alpha-Feto protein (AFP), and Bovine-Serum-Albumin (BSA), fatty emulsions, hot-melt-extrudates and nanoparticles. The oral formulation, in case of a hydrophobic photosensitizer in the present invention, is stabilized using suitable surfactants/solubilizers thus preventing aggregation of the drug in the stomach and until it is absorbed in the duodenum and the small intestine. Oral formulations can be administered in the form of liquid, capsule, tablet, powder, paste or gel. Formulated drugs can be administered orally as one single dose or in multiple doses before administering PDT. In one embodiment Temoporfin (m-THPC) is used as a photosensitizer in the oral formulations. Temoporfin like many hydrophobic photosensitizers are especially suitable to be administered orally because there is no known enzyme system in the mammalian body which can metabolize Temoporfin or similar photosensitizers. Temoporfin can reach the blood system unchanged and fully active after absorption of the formulation in the gastrointestinal tract.

Oral formulations for tetrapyrrole derivatives

Pharmaceutical liposomal formulations are described for photodynamic therapy comprising a, hydrophobic porphyrin photosensitizer, a monosaccharide and one or more synthetic phospholipids, which are stable in storage especially through freeze-drying process. The liposomal formulations provide therapeutically effective amounts of the photosensitizer for intravenous administration. In particular derivatives of chlorins and bacteriochlorins, such as temoporfin, are, hydrophobic photosensitizers whose efficacy and safety are enhanced by such liposomal formulations. The formulation can be efficiently freeze-dried preserving the size of the liposomal vehicles, and the content of a therapeutically effective amount of the photosensitizer, due to the selection of phospholipids and monosaccharides. The invention also relates to liposome compositions formed upon reconstitution with an aqueous vehicle. The freeze-dried formulation upon reconstitution with a suitable aqueous vehicle forms liposomes that are useful for intravenous administration.

Liposomal formulations of hydrophobic photosensitizer for photodynamic therapy

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Cöbe/Marburg, Germany

Alfred Fahr