title: New approach to improve encapsulation and antitumor activity of doxorubicin loaded in solid lipid nanoparticles.
abstract: This work aimed to develop solid lipid nanoparticles (SLNs) loaded with doxorubicin evaluating the influence of docosahexaenoic acid (DHA), a polyunsaturated fatty acid that enhances the activity of anticancer drugs, on drug encapsulation efficiency (EE). The SLN were characterized for size, zeta potential, entrapment efficiency (EE) and drug release. Studies of in vitro antitumor activity and cellular uptake were also conducted. The reduction in particle size (from 127 ± 14 to 94 ± 1 nm) and negative charges were obtained for SLN loaded with DHA and triethanolamine (TEA), amine used to increase the solubility of doxorubicin in melted lipid. The EE was significantly improved from 36 ± 4% to 99 ± 2% for SLN without and with DHA at 0.4%, respectively. The doxorubicin release in a slightly acid medium (pH 5.0) was higher than that observed at physiological pH. The in vitro studies clearly showed the higher cytotoxicity of doxorubicin-DHA-loaded SLN than free doxorubicin+DHA on human lung tumor cell line (A549) and the improved cellular uptake achieved with the drug encapsulation can be an explanation. These findings suggest that DHA-doxorubicin-loaded SLN is a promising alternative for the treatment of cancer.
authors.affiliation: Department of Phamaceutics, Faculty of Pharmacy, Federal University of Minas Gerais (UFMG), Av Antônio Carlos, 6627, Campus Pampulha, CEP 31270-901, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Samuel Vidal
authors.initials: SV
authors.lastname: Mussi
authors.forename: Renata Carvalho
authors.initials: RC
authors.lastname: Silva
authors.forename: Mônica Cristina de
authors.initials: MC
authors.lastname: Oliveira
authors.forename: Carolina Madeira
authors.initials: CM
authors.lastname: Lucci
authors.forename: Ricardo Bentes de
authors.initials: RB
authors.lastname: Azevedo
authors.forename: Lucas Antônio Miranda
authors.initials: LA
authors.lastname: Ferreira
mesh_terms: D020003:1-Octanol / Q000737:chemistry; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000737:chemistry; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004281:Docosahexaenoic Acids / Q000737:chemistry; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry; D006801:Humans; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry / Q000648:ultrastructure; D010316:Particle Size; D014867:Water / Q000737:chemistry
chemical_list: D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D014867:Water; D004281:Docosahexaenoic Acids; D004317:Doxorubicin; D020003:1-Octanol