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1.
Pharmaceutics ; 12(5)2020 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-32384817

RESUMO

Oxidative damage has been linked to a number of diseases. Oleuropein (OLE), a natural occurring polyphenol from olive leaves (Olea europaea L.), is known to be a potent antioxidant compound with inherent instability and compromised bioavailability. Therefore, in this work, nanostructured lipid carriers (NLCs) were proposed for OLE encapsulation to protect and improve its antioxidant efficacy. The lipid matrix, composed of olive oil and Precirol, was optimized prior to OLE encapsulation. The characterization of the optimized oleuropein-loaded NLCs (NLC-OLE) showed a mean size of 150 nm, a zeta potential of -21 mV, an encapsulation efficiency of 99.12%, sustained release profile, and improved radical scavenging activity. The cellular in vitro assays demonstrated the biocompatibility of the NLCs, which were found to improve and maintain OLE antioxidant efficacy in the A549 and CuFi-1 lung epithelial cell lines, respectively. Overall, these findings suggest a promising potential of NLC-OLE to further design a pulmonary formulation for OLE delivery in lung epithelia.

2.
Nanomedicine ; 18: 101-111, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30849549

RESUMO

The usefulness of nanotechnology to increase the bioavailability of drugs and decrease their toxicity may be a tool to deal with multiresistant P. aeruginosa (Mr-Pa) respiratory infections. We describe the preparation and the in vivo efficacy and safety of sodium colistimethate-loaded nanostructured lipid carriers (SCM-NLC) by the pulmonary and intramuscular routes. Nanoparticles showed 1-2 mg/L minimum inhibitory concentration against eight extensively drug-resistant P. aeruginosa strains. In vivo, SCM-NLC displayed significantly lower CFU/g lung than the saline and similar to that of the free SCM, even the dose in SCM-NLC group was lower than free SCM. There was no tissue damage related to the treatments. Biodistribution assessments showed a mild systemic absorption after nebulization and a notorious absorption after IM route. Altogether, it could be concluded that SCM-NLC were effective against P. aeruginosa in vivo, not toxic and distribute efficiently to the lung and liver after pulmonary or intramuscular administrations.


Assuntos
Colistina/análogos & derivados , Portadores de Fármacos/química , Lipídeos/química , Pulmão/microbiologia , Nanoestruturas/química , Pseudomonas aeruginosa/efeitos dos fármacos , Animais , Colistina/administração & dosagem , Colistina/efeitos adversos , Colistina/farmacologia , Feminino , Inflamação/patologia , Injeções Intramusculares , Pulmão/patologia , Camundongos Endogâmicos BALB C , Testes de Sensibilidade Microbiana , Nanoestruturas/toxicidade , Nanoestruturas/ultraestrutura , Distribuição Tecidual/efeitos dos fármacos , Testes de Toxicidade , Resultado do Tratamento
3.
Int J Pharm ; 498(1-2): 263-73, 2016 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-26705155

RESUMO

Among the pathogens that affect cystic fibrosis (CF) patients, Pseudomonas aeruginosa is the most prevalent. As a way to fight against this infection, nanotechnology has emerged over the last decades as a promising alternative to overcome resistance to antibiotics in infectious diseases. The goal of this work was to elaborate and characterize lipid nanoparticles for pulmonary delivery of tobramycin. Tobramycin-loaded nanostructured lipid carriers (Tb-NLCs) were prepared by hot melt homogenization technique. In addition, nanoparticles labeled with infrared dye (IR-NLCs) were used to investigate their in vivo performance after pulmonary administration. Tb-NLCs displayed a mean diameter size around 250 nm, high drug encapsulation (93%) and sustained release profile. Tb-NLCs showed to be active against clinically isolated P. aeruginosa. Moreover, Tb-NLCs did not decrease cell viability and were able to overcome an artificial mucus barrier in the presence of mucolytics agents. During the in vivo assay, IR-NLCs were administered to several mice by the intratracheal route using a Penn Century device. Next, the biodistribution of the nanoparticles was analyzed at different time points showing a wide nanosystem distribution in the lungs. Altogether, tobramycin-loaded NLCs seem to us an encouraging alternative to the currently available CF therapies.


Assuntos
Fibrose Cística/tratamento farmacológico , Sistemas de Liberação de Medicamentos/métodos , Nanoestruturas/administração & dosagem , Infecções por Pseudomonas/tratamento farmacológico , Pseudomonas aeruginosa/efeitos dos fármacos , Tobramicina/administração & dosagem , Administração por Inalação , Animais , Fibrose Cística/metabolismo , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/metabolismo , Feminino , Humanos , Lipídeos , Camundongos , Camundongos Endogâmicos BALB C , Infecções por Pseudomonas/metabolismo , Pseudomonas aeruginosa/fisiologia , Tobramicina/metabolismo
4.
Int J Pharm ; 477(1-2): 485-94, 2014 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-25445528

RESUMO

Lung impairment is the most life-threatening factor for cystic fibrosis patients. Indeed, Pseudomonas aeruginosa is the main pathogen in the pulmonary infection of these patients. In this work, we developed sodium colistimethate loaded lipid nanoparticles, namely, solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC), as a strategy to enhance the antimicrobial therapy against P. aeruginosa in cystic fibrosis patients. The nanoparticles obtained displayed a 200-400 nm size, high drug entrapment (79-94%) and a sustained drug release profile. Moreover, both SLN and NLC presented antimicrobial activity against clinically isolated P. aeruginosa. The integrity of the nanoparticles was not affected by nebulization through a mesh vibrating nebulizer. Moreover, lipid nanoparticles appeared to be less toxic than free sodium colistimethate in cell culture. Finally, an in vivo distribution experiment showed that nanoparticles spread homogenously through the lung and there was no migration of lipid nanoparticles to other organs, such as liver, spleen or kidneys.


Assuntos
Antibacterianos/administração & dosagem , Colistina/análogos & derivados , Fibrose Cística/tratamento farmacológico , Portadores de Fármacos/química , Lipídeos/química , Nanopartículas/química , Infecções por Pseudomonas/tratamento farmacológico , Pseudomonas aeruginosa/efeitos dos fármacos , Administração por Inalação , Animais , Antibacterianos/farmacocinética , Antibacterianos/uso terapêutico , Antibacterianos/toxicidade , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Colistina/administração & dosagem , Colistina/farmacocinética , Colistina/uso terapêutico , Colistina/toxicidade , Fibrose Cística/microbiologia , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Humanos , Camundongos , Testes de Sensibilidade Microbiana , Tamanho da Partícula , Infecções por Pseudomonas/microbiologia , Propriedades de Superfície , Distribuição Tecidual
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