title: Cellular and vascular effects of the photodynamic agent temocene are modulated by the delivery vehicle.
abstract: The effects of the drug delivery system on the PDT activity, localization, and tumor accumulation of the novel photosensitizer temocene (the porphycene analogue of temoporfin or m-tetrahydroxyphenyl chlorin) were investigated against the P815 tumor, both in vitro and in DBA/2 tumor bearing mice. Temocene was administered either free (dissolved in PEG(400)/EtOH mixture), or encapsulated in Cremophor EL micelles or in DPPC/DMPG liposomes, chosen as model delivery vehicles. The maximum cell accumulation and photodynamic activity in vitro was achieved with the free photosensitizer, while temocene in Cremophor micelles hardly entered the cells. Notwithstanding, the micellar formulation showed the best in vivo response when used in a vascular regimen (short drug light interval), whereas liposomes were found to be an efficient drug delivery system for a tumor cell targeting strategy (long drug-light interval). PEG/EtOH formulation was discarded for further in vivo experiments as it provoked lethal toxic effects caused by photosensitizer aggregation. These results demonstrate that drug delivery systems modulate the vascular and cellular outcomes of photodynamic treatments with temocene.
authors: Molecular Engineering Group, IQS School of Engineering, Universitat Ramon Llull, Barcelona, Spain.
authors: María
authors: M
authors: García-Díaz
authors: Masayoshi
authors: M
authors: Kawakubo
authors: Pawel
authors: P
authors: Mroz
authors: M Lluïsa
authors: ML
authors: Sagristà
authors: Margarita
authors: M
authors: Mora
authors: Santi
authors: S
authors: Nonell
authors: Michael R
authors: MR
authors: Hamblin
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry; D005990:Glycerol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D008027:Light; D008081:Liposomes; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D008823:Micelles; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000008:administration & dosage* / Q000737:chemistry; D011166:Porphyrins / Q000008:administration & dosage* / Q000737:chemistry; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D004337:Drug Carriers; D008081:Liposomes; D008823:Micelles; D017319:Photosensitizing Agents; D011166:Porphyrins; C577851:temocene; C000515:cremophor EL; D005990:Glycerol