title: Fluorescence and absorption assessment of a lipid mTHPC formulation following topical application in a non-melanotic skin tumor model.
abstract: Although the benefits of topical sensitizer administration have been confirmed for photodynamic therapy (PDT), ALA-induced protoporphyrin IX is the only sensitizer clinically used with this administration route. Unfortunately, ALA-PDT results in poor treatment response for thicker lesions. Here, selectivity and depth distribution of the highly potent sensitizer meso-tetra(hydroxyphenyl)chlorin (mTHPC), supplied in a novel liposome formulation was investigated following topical administration for 4 and 6 h in a murine skin tumor model. Extraction data indicated an average [+/- standard deviation (SD)] mTHPC concentration within lesions of 6.0(+/-3.1) ngmg tissue with no significant difference (p<0.05) between 4- and 6-h application times and undetectable levels of generalized photosensitivity. Absorption spectroscopy and chemical extraction both indicated a significant selectivity between lesion and normal surrounding skin at 4 and 6 h, whereas the more sensitive fluorescence imaging setup revealed significant selectivity only for the 4-h application time. Absorption data showed a significant correlation with extraction, whereas the results from the fluorescence imaging setup did not correlate with the other methods. Our results indicate that this sensitizer formulation and administration path could be interesting for topical mTHPC-PDT, decreasing the effects of extended skin photosensitivity associated with systemic mTHPC administration.
authors.affiliation: Lund University, Department of Physics, P.O. Box 118, SE-221 00 Lund, Sweden.
authors.forename: Ann
authors.initials: A
authors.lastname: Johansson
authors.forename: Jenny
authors.initials: J
authors.lastname: Svensson
authors.forename: Niels
authors.initials: N
authors.lastname: Bendsoe
authors.forename: Katarina
authors.initials: K
authors.lastname: Svanberg
authors.forename: Eleni
authors.initials: E
authors.lastname: Alexandratou
authors.forename: Maria
authors.initials: M
authors.lastname: Kyriazi
authors.forename: Dido
authors.initials: D
authors.lastname: Yova
authors.forename: Susanna
authors.initials: S
authors.lastname: Gräfe
authors.forename: Tilmann
authors.initials: T
authors.lastname: Trebst
authors.forename: Stefan
authors.initials: S
authors.lastname: Andersson-Engels
mesh_terms: D000287:Administration, Topical; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage; D004195:Disease Models, Animal; D004337:Drug Carriers / Q000737:chemistry; D008055:Lipids / Q000737:chemistry; D008081:Liposomes / Q000737:chemistry*; D008297:Male; D008545:Melanoma / Q000188:drug therapy / Q000473:pathology; D008652:Mesoporphyrins / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D051379:Mice; D008812:Mice, Hairless; D008856:Microscopy, Fluorescence; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D012869:Skin Absorption; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D008055:Lipids; D008081:Liposomes; D008652:Mesoporphyrins; D017319:Photosensitizing Agents; C072269:temoporfin