Abstract
HypothesisDroplet size in microfluidic devices is affected by wettability of the microfluidic channels. Three-dimensional countercurrent flow focusing using assemblies of chemically inert glass capillaries is expected to minimize wetting of the channel walls by the organic solvent. ExperimentsMonodispersed polycaprolactone and poly(lactic acid) particles with a diameter of 18–150μm were produced by evaporation of solvent (dichloromethane or 1:2 mixture of chloroform and toluene) from oil-in-water or water-in-oil-in-water emulsions produced in three-dimensional flow focusing glass capillary devices. The drop generation behaviour was simulated numerically using the volume of fluid method. FindingsThe numerical results showed good agreement with high-speed video recordings. Monodispersed droplets were produced in the dripping regime when the ratio of the continuous phase flow rate to dispersed phase flow rate was 5–20 and the Weber number of the dispersed phase was less than 0.01. The porosity of polycaprolactone particles increased from 8 to 62% when 30wt% of the water phase was incorporated in the organic phase prior to emulsification. The inner water phase was loaded with 0.156wt% lidocaine hydrochloride to achieve a sustained drug release. 26% of lidocaine was released after 1h and more than 93% of the drug was released after 130h.
Highlights
Porous microparticles made from synthetic biodegradable polymers are increasingly being investigated for use in medical, biotechnological, and pharmaceutical applications in areas such as contrast-enhanced ultrasound imaging [1], controlled drug delivery [2] and cell growth in tissue engineering scaffolds [3]
The oil phase in water-in-oil-in-water (W/O/W) emulsions was a mixture of 1–3 wt% poly(DL-lactic acid) (PLA, Mw = 15,000 g molÀ1, Polysciences, Inc., US) or polycaprolactone (PCL, Mw = 14,000 g molÀ1, Sigma–Aldrich, UK) dissolved in dichloromethane (DCM, High performance liquid chromatography (HPLC) grade, Fisher Scientific, UK) or 1:2 mixture of chloroform and toluene. 5–10 wt% polyglycerol polyricinoleate (PGPR, E476, Abitec Ltd., New Milton, UK) was added in the oil phase to prevent coalescence of inner water droplets, and 0.1– 2 mM Nile red to help in visual identification of the particles
We have developed a cheap and reliable microfluidic method for controllable production of biodegradable microparticles based on countercurrent flow focusing in a glass capillary device and solvent evaporation
Summary
Porous microparticles made from synthetic biodegradable polymers are increasingly being investigated for use in medical, biotechnological, and pharmaceutical applications in areas such as contrast-enhanced ultrasound imaging [1], controlled drug delivery [2] and cell growth in tissue engineering scaffolds [3]. Monodisperse poly(lactic acid) (PLA) and polycaprolactone (PCL) microparticles with water droplets embedded within the polymer matrix were produced using a novel approach based on emulsification in a 3D (axisymmetric) flow focusing glass capillary device [19,20]. These particles can be used as intermediate products in the production of UCAs. The main objective was to investigate the effects of phase flow rates and geometry of the device on the droplet and particle size and droplet formation behaviour. The modelling results were used to better understand the mechanisms of drop generation
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