title: Influence of aqueous media properties on aggregation and solubility of four structurally related meso-porphyrin photosensitizers evaluated by spectrophotometric measurements.
abstract: Porphyrin photosensitizers tend to aggregate in aqueous solutions even in the micromolar concentration range. This is a challenge during formulation of e.g., parenteral preparations for photodynamic cancer therapy, or preparations for local or topical administration in antimicrobial photodynamic therapy. Monomerization is essential to achieve biocompatible drug formulations of high bioavailability and physiological response (i.e., photoreactivity) and low toxicity. The aggregation and solubilization of four structurally related meso-tetraphenyl porphyrin photosensitizers with nonionic (4-hydroxy), anionic (4-sulphonate; 4-carboxy) and cationic (4-trimethylanilinium) substituents were evaluated in various vehicles by use of UV-Vis spectroscopy. Substituents, overall charge and charge distribution influenced the pKa-values and interaction of the porphyrins with different solvents, excipients and impurities. Modification of medium polarity and solubilization by the nonionic surfactant Tween 80 adjusted the acid-base equilibria and increased the solubility by reduction of porphyrin aggregation. The selected porphyrins were sensitive towards ionic strength, temperature and inorganic impurities to various extents. The results will be further used during development of parenteral and topical formulations of porphyrin photosensitizers for use in photodynamic therapy of cancer and bacterial infections.
authors.affiliation: Jan Sobczyński, Department of Pharmacy, School of Pharmacy, University of Oslo, PO. Box 1068 Blindern, N-0316 Oslo, Norway. jan.sobczynski@farmasi.uio.no
authors.forename: J
authors.initials: J
authors.lastname: Sobczyński
authors.forename: H H
authors.initials: HH
authors.lastname: Tønnesen
authors.forename: S
authors.initials: S
authors.lastname: Kristensen
mesh_terms: D000287:Administration, Topical; D002626:Chemistry, Pharmaceutical; D005290:Ferric Compounds / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D007202:Indicators and Reagents; D000432:Methanol; D008958:Models, Molecular; D019999:Pharmaceutical Solutions; D014677:Pharmaceutical Vehicles; D017319:Photosensitizing Agents / Q000737:chemistry*; D011136:Polysorbates; D011166:Porphyrins / Q000737:chemistry*; D012995:Solubility; D012997:Solvents; D013056:Spectrophotometry, Ultraviolet; D013501:Surface-Active Agents; D014867:Water
chemical_list: D005290:Ferric Compounds; D007202:Indicators and Reagents; D019999:Pharmaceutical Solutions; D014677:Pharmaceutical Vehicles; D017319:Photosensitizing Agents; D011136:Polysorbates; D011166:Porphyrins; D012997:Solvents; D013501:Surface-Active Agents; D014867:Water; D000432:Methanol