title: Development of cationic solid lipid nanoparticles with factorial design-based studies for topical administration of doxorubicin.
abstract: Topical chemotherapy using doxorubicin, a powerful anticancer drug, can be used as an alternative with reduced systemic toxicity when treating skin cancer. The aim of the present work was to use factorial design-based studies to develop cationic solid lipid nanoparticles containing doxorubicin; further investigations into the influence of these particles on the drug's cytotoxicity and cellular uptake in B16F10 murine melanoma cells were performed. A 32 full factorial design was applied for two different lipid phases; one phase used stearic acid and the other used a 1:2 mixture of stearic acid and glyceryl behenate. The two factors investigated included the ratio between the lipid and the water phase and the ratio between the surfactant (poloxamer) and the co-surfactant (cetylpyridinium chloride). It was observed that the studied factors did not affect the mean diameter or the polydispersity of the obtained nanoparticles; however, they did significantly affect the zeta potential values. Optimised formulations with particle sizes ranging from 251 to 306 nm and positive zeta potentials were selected for doxorubicin incorporation. High entrapment efficiencies were achieved (97%) in formulations with higher amounts of stearic acid, suggesting that cationic charges on doxorubicin molecules may interact with the negative charges in stearic acid. Melanoma culture cell experiments showed that cationic solid lipid nanoparticles without drug were not cytotoxic to melanoma cells. The encapsulation of doxorubicin significantly increased cytotoxicity, indicating the potential of these nanoparticles for the treatment of skin cancer.
authors.affiliation: School of Pharmaceutical Sciences of Ribeirão Preto University of São Paulo. Av. do Café s/n, 14040-903, Ribeirão Preto, SP Brazil.
authors.forename: Stephânia F
authors.initials: SF
authors.lastname: Taveira
authors.forename: Luciana M P de Campos
authors.initials: LM
authors.lastname: Araújo
authors.forename: Danielle C A S
authors.initials: DC
authors.lastname: de Santana
authors.forename: Auro
authors.initials: A
authors.lastname: Nomizo
authors.forename: Luiz Alexandre P
authors.initials: LA
authors.lastname: de Freitas
authors.forename: Renata F V
authors.initials: RF
authors.lastname: Lopez
mesh_terms: D000287:Administration, Topical; D000704:Analysis of Variance; D000818:Animals; D002412:Cations / Q000737:chemistry; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry* / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000737:chemistry*; D005227:Fatty Acids / Q000737:chemistry; D008546:Melanoma, Experimental / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D012107:Research Design; D013229:Stearic Acids / Q000737:chemistry
chemical_list: D002412:Cations; D004337:Drug Carriers; D005227:Fatty Acids; D013229:Stearic Acids; C086409:glyceryl behenate; C031183:stearic acid; D004317:Doxorubicin