Temoporfin-loaded liposomes: Physicochemical characterization

• Published in: European journal of pharmaceutical sciences Vol. 40; no. 4; pp. 305 - 315
• Main Authors: Kuntsche, Judith, Freisleben, Ines, Steiniger, Frank, Fahr, Alfred
• Format: Journal Article
• Language: English
• Published: Kindlington Elsevier B.V 11-07-2010; Elsevier
• Subjects: Biological and medical sciences; Calorimetry, Differential Scanning; Chemical Phenomena; Chemistry, Pharmaceutical; Cryoelectron Microscopy; Drug Carriers - chemistry; Drug Stability; Fatty Acids - chemistry; Foslip; Freeze Drying; General pharmacology; Liposomes; Liposomes - chemistry; Liposomes - ultrastructure; Lyophilization; Medical sciences; Mesoporphyrins - chemistry; Micelles; Pegylation; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Phase Transition; Photosensitizing Agents - chemistry; Physicochemical characterization; Polyethylene Glycols - chemistry; Temoporfin; Transition Temperature; Unilamellar Liposomes - chemistry; Water - analysis; Physicochemical characterization; Liposomes; Lyophilization; Foslip; Temoporfin; Pegylation; Pharmaceutical technology; Liposome; Pegylated form; Photosensitizer; Porphyrin derivatives; Physicochemical properties
• ISSN: 0928-0987; 1879-0720
• DOI: 10.1016/j.ejps.2010.04.005

Temoporfin (mTHPC) is a potent but highly hydrophobic second-generation photosensitizer and has been approved for the palliative treatment of patients with advanced head and neck cancer by photodynamic therapy. Liposome formulations have been evaluated as carrier system for this drug to overcome some problems associated with the commercial formulation Foscan
® where the drug is dissolved in a mixture of water-free ethanol and propylene glycol.
The present study focuses on the physicochemical characterization of different liposome formulations with special emphasis on the influence of drug incorporation on the thermal phase behavior of the liposomes. In addition to conventional liposomes, pegylated lipids were used for the preparation of “stealth” liposomes. The dispersions as well as freeze-dried formulations were characterized by photon correlation spectroscopy, differential scanning calorimetry and cryo-electron microscopy.
Incorporation of temoporfin resulted in a distinct concentration dependent decrease of the main phase transition of the liposomes. In case of liposomes based on dipalmitoylphosphatidylcholine/-glycerol, phase transition was close or even below body temperature. In contrast, if phospholipids with longer fatty acid chains (distearoylphosphatidylcholine/-glycerol) were used, phase transitions were well above body temperature even at high drug load. Size and thermal behavior were not distinctly influenced by the addition of pegylated lipids but cryo-electron microscopic investigations indicate the presence of micellar structures in addition to vesicles. Lyophilization and reconstitution led to an alteration in the morphology but had overall no distinct influence on the colloidal stability.