title: Development, characterization, and photocytotoxicity assessment on human melanoma of chloroaluminum phthalocyanine nanocapsules.
abstract: In this work we have developed nanocapsules containing chloroaluminum phthalocyanine (ClAlPc) and assessed their phototoxic action on WM1552C, WM278, and WM1617 human melanoma cell lines. The ClAlPc-loaded nanocapsules were prepared by the nanoprecipitation method and optimized by means of a 2(3) full factorial design. The ClAlPc nanocapsules were characterized by particle size and distribution, zeta potential, morphology, encapsulation efficiency, singlet oxygen production, stability, and phototoxic action on melanoma cells. Both the development and optimization studies revealed that stable colloidal formulations could be obtained by using 1.75% (w/v) soybean lecithin, 1.25% (w/v) Poloxamer 188, 2.5% (v/v) soybean oil, and 0.75% (w/v) poly(D,L-lactide-co-glycolide). The nanocapsules had a mean diameter of 230 nm, homogeneous size distribution (polydispersity index<0.3), and negative zeta potential (about -30 mV). Their morphology was spherical, with evident polymer membrane coating droplet. The encapsulation efficiency was 70%, as expected for hydrophobic drugs, and the nanoencapsulated ClAlPc was able to produce high singlet oxygen quantum yield. ClAlPc nanocapsules exhibited good physical stability over a 12-month period. WM1552C primary melanoma cells were more sensitive (p<0.05) to the phototoxic effect elicited by ClAlPc nanocapsules (0.3 μg ml(-1)) under light irradiation at 20 mJ cm(-2). On the other hand, the cell survival percentage for all the melanoma cell lines treated with the highest light dose (150 mJ cm(-2)) was lower than 10%. In summary, ClAlPc nanoencapsulation could enable application of this hydrophobic photosensitizer in the treatment of malignant melanoma with the use of both low sensitizer drug concentration and light dose.
authors.affiliation: Departamento de Ciências Farmacêuticas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP), Universidade de São Paulo, Ribeirão Preto-SP, Brazil.
authors.forename: Marigilson P
authors.initials: MP
authors.lastname: Siqueira-Moura
authors.forename: Fernando L
authors.initials: FL
authors.lastname: Primo
authors.forename: Enilza M
authors.initials: EM
authors.lastname: Espreafico
authors.forename: Antonio C
authors.initials: AC
authors.lastname: Tedesco
mesh_terms: D016923:Cell Death / Q000187:drug effects / Q000528:radiation effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002626:Chemistry, Pharmaceutical; D004355:Drug Stability; D006801:Humans; D007211:Indoles / Q000737:chemistry / Q000494:pharmacology*; D008027:Light; D053769:Nanocapsules / Q000737:chemistry* / Q000648:ultrastructure; D009942:Organometallic Compounds / Q000737:chemistry / Q000494:pharmacology*; D010316:Particle Size; D026082:Singlet Oxygen / Q000378:metabolism; D055672:Static Electricity
chemical_list: D007211:Indoles; D053769:Nanocapsules; D009942:Organometallic Compounds; C044797:chloroaluminum phthalocyanine; D026082:Singlet Oxygen
keywords: Chloroaluminum phthalocyanine; Factorial design; Melanoma skin cancer; Nanocapsules; Photocytotoxicity; Photodynamic therapy