RESUMO
The development of versatile carriers to deliver chemotherapeutic agents to specific targets with establishing drug release kinetics and minimum undesirable side effects is becoming a promising relevant tool in the medical field. Magnetic hybrid nanostructured lipid carriers (NLC) were prepared by incorporation of 1,8-cineole (CN, a monoterpene with antiproliferative properties) and maghemite nanoparticles (MNPs) into a hybrid matrix composed of myristyl myristate coated with chitosan. Hybrid NLC characterized by DLS and TEM confirmed the presence of positively charged spherical nanoparticles of around 250 nm diameter and +10.2 mV of Z-potential. CN encapsulation into the lipid core was greater than 75 % and effectively released in 24 h. Modification of the crystalline structure of nanoparticles after incorporation of CN and MNPs was observed by XRD, DSC, and TGA analyses. Superparamagnetic NLC behavior was verified by recording the magnetization using a vibrating scanning magnetometer. NLC resulted in more cytotoxic than free CN in HepG2 and A549 cell lines. Particularly, viability inhibition of HepG2 and A549 cells was increased from 35 % to 55 % and from 38 % to 61 %, respectively, when 8 mM CN was incorporated into the lipid NPs at 24 h. Green fluorescent-labeled NLC with DIOC18 showed an enhanced cellular uptake with chitosan-coated NLC. Besides, no cytotoxicity of the formulations in normal WI-38 cells was observed, suggesting that the developed hybrid NLC system is a safe and good potential candidate for the selective delivery and potentiation of anticancer drugs.
Assuntos
Antineoplásicos , Nanopartículas , Nanoestruturas , Antineoplásicos/farmacologia , Portadores de Fármacos , Eucaliptol , Lipídeos , Fenômenos Magnéticos , Tamanho da PartículaRESUMO
In the global context of an imminent emergence of multidrug-resistant microorganisms, the present work combined the use of nanotechnology and the therapeutic benefits of natural compounds as a strategy to potentiate antimicrobial action of the wide-spectrum antibiotic Ofloxacin (Ofx). Hybrid solid lipid nanoparticles (SLN) were synthesized by incorporation of chitosan (Chi, a cationic biopolymer with antimicrobial activity) and eugenol (Eu, a phenolic compound that interferes with bacterial quorum sensing) into a lipid matrix by hot homogenization/ultrasonication method. The developed SLN/Chi/Eu sustainably released the encapsulated Ofx for 24â¯h. Characterization by DLS, TEM, DSC, TGA and XRD revealed the presence of positively charged spherical nanoparticles with diameters around 300â¯nm and Ofx entrapped in amorphous state. The SLN exhibited an enhanced bactericidal activity against Pseudomonas aeruginosa and Staphylococcus aureus. The minimum inhibitory concentration (MIC) for free and nanoencapsulated Ofx formulations was below 1.0⯵g/ml. The MIC values decreased by 6.1- to 16.1-fold when Ofx was encapsulated in SLN/Chi/Eu. Fluorescent-labeled nanoparticles had the ability to interact with the bacterial cell membrane. Selective toxicity of SLN/Chi/Eu-Ofx was tested in the range of 0.3-30.0⯵g/ml and showed no toxicity up to 3.0⯵g/ml Ofx in human cell models (A549 and Wi-38) at 24â¯h and 48â¯h exposure. It was proved that the administration of hybrid SLN to mice by dry powder inhalation reached therapeutic Ofx levels in lungs.