title: Lipid vesicles loading aluminum phthalocyanine chloride: Formulation properties and disaggregation upon intracellular delivery.
abstract: Aluminum phthalocyanine chloride (AlClPc) is a second-generation photodynamic therapy (PDT) photosensitizer characterized for its high hydrophobicity and self-aggregation tendency in aqueous media, which hamper its potential application. Aiming at AlClPc solubilization we proposed here the use of 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) and 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) at different proportions to form mixed lipid vesicles (LVs) as a drug delivery system. LVs were prepared by ethanol injection method and formed nano-sized vesicles (about 100nm) with suitable polydispersity index, negative zeta potential, and stable in aqueous medium for at least 50days. AlClPc strongly interacts with LV (high binding constant values), especially due to aluminum-phosphate specific interactions, which gives a surface localization to AlClPc molecules as demonstrated by fluorescence quenching data. Anisotropy, static and time-resolved fluorescence measurements corroborated with these results and demonstrated that AlClPc self-aggregation occurred even in the liposomes. However, formulation uptake by oral squamous cell carcinoma (OSCC) the AlClPc was distributed in cellular organelles and suffered a disaggregation process demonstrated by fluorescence life-time imaging microscopy. This amazing behavior is new and increases the scientific knowledge about the intracellular mechanism of action of PDT photosensitizers. In addition, these results open a new perspective to the potential use of AlClPc-LV formulations for photodynamic treatment.
authors.affiliation: Departamento de Química, Laboratório de Fotobiologia e Fotomedicina, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, 14040-901 Ribeirão Preto, SP, Brazil. Electronic address: italocalori@hotmail.com.
authors.forename: Italo Rodrigo
authors.initials: IR
authors.lastname: Calori
authors.affiliation: Departamento de Química, Laboratório de Fotobiologia e Fotomedicina, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, 14040-901 Ribeirão Preto, SP, Brazil. Electronic address: atedesco@usp.br.
authors.forename: Antonio Claudio
authors.initials: AC
authors.lastname: Tedesco
mesh_terms: D045744:Cell Line, Tumor; D000431:Ethanol / Q000737:chemistry; D005454:Fluorescence Polarization; D005997:Glycerylphosphorylcholine / Q000031:analogs & derivatives / Q000737:chemistry; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007211:Indoles / Q000737:chemistry / Q000378:metabolism*; D008081:Liposomes / Q000737:chemistry / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D009942:Organometallic Compounds / Q000737:chemistry / Q000378:metabolism*; D010713:Phosphatidylcholines / Q000737:chemistry; D017319:Photosensitizing Agents / Q000737:chemistry / Q000378:metabolism*
chemical_list: D007211:Indoles; D008081:Liposomes; D009942:Organometallic Compounds; D010713:Phosphatidylcholines; D017319:Photosensitizing Agents; C044797:chloroaluminum phthalocyanine; D000431:Ethanol; D005997:Glycerylphosphorylcholine; C010942:1,2-distearoyllecithin; C017251:1,2-oleoylphosphatidylcholine
keywords: Aggregation; Aluminum phthalocyanine chloride; Drug delivery system; Photodynamic therapy; Uptake cellular