title: Increased cellular uptake of lauryl gallate loaded in superparamagnetic poly(methyl methacrylate) nanoparticles due to surface modification with folic acid.
abstract: Lauryl gallate loaded in superparamagnetic poly(methyl methacrylate) nanoparticles surface modified with folic acid were synthesized by miniemulsion polymerization in just one step. In vitro biocompatibility and cytotoxicity assays on L929 (murine fibroblast), human red blood, and HeLa (uterine colon cancer) cells were performed. The effect of folic acid at the nanoparticles surface was evaluated through cellular uptake assays in HeLa cells. Results showed that the presence of folic acid did not affect substantially the polymer particle size (~120 nm), the superparamagnetic behavior, the encapsulation efficiency of lauryl gallate (~87 %), the Zeta potential (~38 mV) of the polymeric nanoparticles or the release profile of lauryl gallate. The release profile of lauryl gallate from superparamagnetic poly(methyl methacrylate) nanoparticles presented an initial burst effect (0-1 h) followed by a slow and sustained release, indicating a biphasic release system. Lauryl gallate loaded in superparamagnetic poly(methyl methacrylate) nanoparticles with folic acid did not present cytotoxicity effects on L929 and human red blood cells. However, free lauryl gallate presented significant cytotoxic effects on L929 and human red blood cells at all tested concentrations. The presence of folic acid increased the cytotoxicity of lauryl gallate loaded in nanoparticles on HeLa cells due to a higher cellular uptake when HeLa cells were incubated at 37 °C. On the other hand, when the nanoparticles were incubated at low temperature (4 °C) cellular uptake was not observed, suggesting that the uptake occurred by folate receptor mediated energy-dependent endocytosis. Based on presented results our work suggests that this carrier system can be an excellent alternative in targeted drug delivery by folate receptor.
authors: Department of Chemical Engineering and Food Engineering, Federal University of Santa Catarina, Florianópolis, Brazil.
authors: Paulo Emilio
authors: PE
authors: Feuser
authors: Department of Biochemistry and Molecular Biology, Federal University of Paraná, Curitiba, Brazil.
authors: Juan Marcelo Carpio
authors: JM
authors: Arévalo
authors: Laboratório de Resonancias Magnéticas, Centro Atómico Bariloche & CONICET, San Carlos de Bariloche, Argentina.
authors: Enio Lima
authors: EL
authors: Junior
authors: Department of Cellular Biology, Federal University of Paraná, Curitiba, Brazil.
authors: Gustavo Rodrigues
authors: GR
authors: Rossi
authors: Department of Cellular Biology, Federal University of Paraná, Curitiba, Brazil.
authors: Edvaldo
authors: E
authors: da Silva Trindade
authors: Department of Biochemistry and Molecular Biology, Federal University of Paraná, Curitiba, Brazil.
authors: Maria Eliane Merlin
authors: ME
authors: Rocha
authors: Department of Clinical Analyses, Federal University of Santa Catarina, Florianópolis, Brazil.
authors: Amanda Virtuoso
authors: AV
authors: Jacques
authors: Department of Pharmacy, Federal University of Rio Janeiro, Rio de Janeiro, Brazil.
authors: Eduardo
authors: E
authors: Ricci-Júnior
authors: Department of Clinical Analyses, Federal University of Santa Catarina, Florianópolis, Brazil.
authors: Maria Claudia
authors: MC
authors: Santos-Silva
authors: Department of Chemical Engineering and Food Engineering, Federal University of Santa Catarina, Florianópolis, Brazil.
authors: Claudia
authors: C
authors: Sayer
authors: Department of Chemical Engineering and Food Engineering, Federal University of Santa Catarina, Florianópolis, Brazil. pedro.h.araujo@ufsc.br.
authors: Pedro H Hermes
authors: PH
authors: de Araújo
mesh_terms: D000818:Animals; D001672:Biocompatible Materials; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000494:pharmacology; D004705:Endocytosis; D004912:Erythrocytes / Q000166:cytology; D005492:Folic Acid / Q000737:chemistry*; D005707:Gallic Acid / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D006367:HeLa Cells; D006461:Hemolysis; D006801:Humans; D007700:Kinetics; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D051379:Mice; D010316:Particle Size; D019904:Polymethyl Methacrylate / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared; D013499:Surface Properties; D013696:Temperature; D013818:Thermogravimetry
chemical_list: D001672:Biocompatible Materials; D004337:Drug Carriers; D058185:Magnetite Nanoparticles; C008259:lauryl gallate; D005707:Gallic Acid; D019904:Polymethyl Methacrylate; D005492:Folic Acid