RESUMO
We present a versatile continuous microfluidic flow-focusing method for the production of Doxorubicin (DOX) or Tamoxifen (TAM)-loaded poly(D,L-lactic-co-glycolic acid) (PLGA) nanoparticles (NPs). We use a partially water-miscible solvent mixture (dimethyl sulfoxide DMSO+ dichloromethane DCM) as precursor drug/polymer solution for NPs nucleation. We extrude this partially water-miscible solution into an aqueous medium and synthesized uniform PLGA NPs with higher drug loading ability and longer sustained-release ability than conventional microfluidic or batch preparation methods. The size of NPs could be precisely tuned by changing the flow rate ratios, polymer concentration, and volume ratio of DCM to DMSO (VDCM/VDMSO) in the precursor emulsion. We investigated the mechanism of the formation of NPs and the effect of VDCM/VDMSO on drug release kinetics. Our work suggests that this original, rapid, facile, efficient and low-cost method is a promising technology for high throughput NP fabrication. For the two tested drugs, one hydrophilic (Doxorubicin) the other one hydrophobic (Tamoxifen), encapsulation efficiency (EE) as high as 88% and mass loading content (LC) higher than 25% were achieved. This new process could be extended as an efficient and large scale NP production method to benefit to fields like controlled drug release and nanomedicine.
Assuntos
Antibióticos Antineoplásicos/química , Preparações de Ação Retardada/química , Microfluídica/métodos , Nanopartículas/química , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Dimetil Sulfóxido/química , Doxorrubicina/química , Composição de Medicamentos/métodos , Liberação Controlada de Fármacos , Emulsões , Humanos , Cinética , Cloreto de Metileno/química , Nanopartículas/ultraestrutura , Tamanho da Partícula , Solventes/química , Tamoxifeno/química , Água/químicaRESUMO
We study flows of hydrolized polyacrylamide solutions in two dimensional porous media made using microfluidics, for which elastic effects are dominant. We focus on semi-dilute solutions (0.1%-0.4%) which exhibit a strong shear thinning behavior. We systematically measure the pressure drop and find that the effective permeability is dramatically higher than predicted when the Weissenberg number is greater than about 10. Observations of the streamlines of the flow reveal that this effect coincides with the onset of elastic instabilities. Moreover, and importantly for applications, we show using local measurements that the mean flow is modified: it appears to be more uniform at high Weissenberg number than for Newtonian fluids. These observations are compared and discussed using pore network simulations, which account for the effect of disorder and shear thinning on the flow properties.
RESUMO
We explore the flow of highly shear thinning polymer solutions in straight geometry. The strong variations of the normal forces close to the wall give rise to an elastic instability. We evidence a periodic motion close the onset of the instability, which then evolves towards a turbulentlike flow at higher flow rates. Strikingly, we point out that this instability induces genuine drag reduction due to the homogenization of the viscosity profile by the turbulent flow.
