title: A novel tetracationic phthalocyanine as a potential skin phototherapeutic agent.
abstract: An amphiphilic tetracationic derivative of Zn(II)-phthalocyanine (RLP068) was prepared by means of chemical synthesis and was showed to possess efficient photophysical and photosensitizing properties against model biological substrates. RLP068 was incorporated into a gel formulation, which allowed its ready penetration into the epidermal layers, but not into the dermis, of both Balb/c and hairless SKH1 mice after 1-2 h of topical deposition. Pharmacokinetic studies showed that the phthalocyanine thus formulated does not enter the general blood circulation. The epidermis-associated amount of phthalocyanine was sufficient to cause an important cutaneous damage upon irradiation with red light (600-700 nm; 100-180 mW/cm(2), 160 J/cm(2)); the latter was confined to the epidermal area with no apparent diffusion to the underlying dermal layers or appearance of photosensitivity in distal skin areas. A systematic investigation of the interplay among the different parameters (deposition time of the formulated phthalocyanine on mouse skin, irradiation fluence rate and total light fluence) allowed us to identify the minimal phototoxic dose, as well as to define irradiation protocols allowing the repeatability of the phototherapeutic treatment. The potential of RLP068 to act as a PDT agent for cutaneous diseases is briefly discussed.
authors.affiliation: Molteni Farmaceutici, Florence, Italy.
authors.forename: Clara
authors.initials: C
authors.lastname: Fabris
authors.forename: Marina
authors.initials: M
authors.lastname: Soncin
authors.forename: Emanuela
authors.initials: E
authors.lastname: Mazzon
authors.forename: Piergiacomo
authors.initials: P
authors.lastname: Calzavara-Pinton
authors.forename: Fantetti
authors.initials: F
authors.lastname: Lia
authors.forename: Chiti
authors.initials: C
authors.lastname: Giacomo
authors.forename: Donata
authors.initials: D
authors.lastname: Dei
authors.forename: Silvia
authors.initials: S
authors.lastname: Tampucci
authors.forename: Gabrio
authors.initials: G
authors.lastname: Roncucci
authors.forename: Giulio
authors.initials: G
authors.lastname: Jori
mesh_terms: D000818:Animals; D001706:Biopsy; D002412:Cations; D003879:Dermatologic Agents / Q000494:pharmacology; D004058:Diffusion; D004817:Epidermis / Q000378:metabolism; D005260:Female; D005782:Gels; D007211:Indoles / Q000494:pharmacology*; D054833:Isoindoles; D008027:Light; D051379:Mice; D008812:Mice, Hairless; D008807:Mice, Inbred BALB C; D018613:Microscopy, Confocal; D008956:Models, Chemical; D009942:Organometallic Compounds / Q000494:pharmacology*; D017319:Photosensitizing Agents / Q000494:pharmacology*; D010789:Phototherapy / Q000379:methods*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology; D012867:Skin / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors; D015032:Zinc / Q000737:chemistry
chemical_list: D002412:Cations; D003879:Dermatologic Agents; D005782:Gels; D007211:Indoles; D054833:Isoindoles; D009942:Organometallic Compounds; D017319:Photosensitizing Agents; C477806:RLP068; D011838:Radiation-Sensitizing Agents; D015032:Zinc; C013647:phthalocyanine