E. Ekanem

Glass capillary microfluidics for production of monodispersed poly (dl-lactic acid) and polycaprolactone microparticles: Experiments and numerical simulations

HYPOTHESIS Droplet 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. EXPERIMENTS Monodispersed polycaprolactone and poly(lactic acid) particles with a diameter of 18-150 μm 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. FINDINGS The 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 30 wt% of the water phase was incorporated in the organic phase prior to emulsification. The inner water phase was loaded with 0.156 wt% lidocaine hydrochloride to achieve a sustained drug release. 26% of lidocaine was released after 1 h and more than 93% of the drug was released after 130 h.

Structured Biodegradable Polymeric Microparticles for Drug Delivery Produced Using Flow Focusing Glass Microfluidic Devices

Biodegradable poly(DL-lactic acid) (PLA) and poly(lactic-co-glycolic acid) (PLGA) microparticles with tunable size, shape, internal structure and surface morphology were produced by counter-current flow focusing in axisymmetric (3D) glass capillary devices. The dispersed phase was composed of 0.5-2 wt % polymer solution in a volatile organic solvent (ethyl acetate or dichloromethane) and the continuous phase was 5 wt % aqueous poly(vinyl alcohol) solution. The droplets with a coefficient of variation in dripping regime below 2.5% were evaporated to form polymeric particles with uniform sizes ranging between 4 and 30 μm. The particle microstructure and surface roughness were modified by adding nanofiller (montmorillonite nanoclay) or porogen (2-methylpentane) in the dispersed phase to form less porous polymer matrix or porous particles with golf-ball-like dimpled surface, respectively. The presence of 2-4 wt % nanoclay in the host polymer significantly reduced the release rate of paracetamol and prevented the early burst release, as a result of reduced polymer porosity and tortuous path for the diffusing drug molecules. Numerical modeling results using the volume of fluid-continuum surface force model agreed well with experimental behavior and revealed trapping of nanoclay particles in the dispersed phase upstream of the orifice at low dispersed phase flow rates and for 4 wt % nanoclay content, due to vortex formation. Janus PLA/PCL (polycaprolactone) particles were produced by solvent evaporation-induced phase separation within organic phase droplets containing 3% (v/v) PLA/PCL (30/70 or 70/30) mixture in dichloromethane. A strong preferential adsorption of Rhodamine 6G dye onto PLA was utilized to identify PLA portions of the Janus particles by confocal laser scanning microscopy (CLSM). Uniform hemispherical PCL particles were produced by dissolution of PLA domes with acetone.

Dynamics of double emulsion break-up in three phase glass capillary microfluidic devices.

Pinch-off of a compound jet in 3D glass capillary microfluidic device, which combines co-flowing and countercurrent flow focusing geometries, was investigated using an incompressible three-phase axisymmetric Volume of Fluid-Continuum Surface Force (VOF-CSF) numerical model. The model showed good agreement with the experimental drop generation and was capable of predicting formation of core/shell droplets in dripping, narrowing jetting and widening jetting regimes. In dripping and widening jetting regimes, the presence of a vortex flow around the upstream end of the necking thread facilitates the jet break-up. No vortex flow was observed in narrowing jetting regime and pinch-off occurred due to higher velocity at the downstream end of the coaxial thread compared to that at the upstream end. In all regimes, the inner jet ruptured before the outer jet, preventing a leakage of the inner drop into the outer fluid. The necking region moves at the maximum speed in the narrowing jetting regime, due to the highest level of shear at the outer surface of the thread. However, in widening jetting regime, the neck travels the longest distance downstream before it breaks.

Facile microfluidic production of composite polymer core-shell microcapsules and crescent-shaped microparticles

HYPOTHESIS Core-shell microcapsules and crescent-shaped microparticles can be used as picolitre bioreactors for cell culture and microwells for cell trapping/immobilisation, respectively. RESULTS Monodisperse polylactic acid (PLA) core-shell microcapsules with a diameter above 200μm, a shell thickness of 10μm, and 96% water entrapment efficiency were produced by solvent evaporation from microfluidically generated W/O/W emulsion drops with core-shell structure, and used to encapsulate Saccharomyces cerevisiae yeast cells in their aqueous cores. The morphological changes of the capsules stained with Nile red were studied over 14days under different osmotic pressure and pH gradients. FINDINGS The shell retained its integrity under isotonic conditions, but buckling and particle crumbling occurred in a hypertonic solution. When the capsules containing 5wt% aqueous Eudragit® S 100 solution in the core were incubated in 10-4M HCl solution, H+ diffused through the PLA film into the core causing an ionic gelation of the inner phase and its phase separation into polymer-rich and water-rich regions, due to the transition of Eudragit from a hydrophilic to hydrophobic state. Crescent-shaped composite microparticles with Eudragit cores and PLA shells were fabricated by drying core-shell microcapsules with gelled cores, due to the collapse of PLA shells encompassing water-rich crescent regions.

Facile Production of Biodegradable Bipolymer Patchy and Patchy Janus Particles with Controlled Morphology by Microfluidic Routes

Patchy and patchy Janus particles composed of poly(dl-lactic acid) (PLA) and polycaprolactone (PCL) regions were produced with a controlled size, patchiness, composition, and shape anisotropy by microfluidic emulsification and solvent evaporation. Isotropic particles composed of PCL patches embedded in the PLA matrix were produced from relatively small drops with a diameter of 14-25 μm because of the fast solvent extraction as a result of high interfacial area of the particles. Anisotropic patchy Janus particles were formed from large drops, 100-250 μm in diameter. A higher degree of polymer separation was achieved using a higher ratio of dichloromethane to ethyl acetate in the organic phase because of the more pronounced patch coarsening via Ostwald ripening. Janus particles with two fully separated polymer compartments were produced by in situ microfluidic mixing of two separate polymer streams within the formed droplets. The advantage of in situ micromixing is that the particle morphology can be changed continuously in a facile manner during drop generation by manipulating the organic stream flow rates. PCL and PLA domains within the particles were visualized by confocal laser scanning microscopy because of the preferential adsorption of rhodamine 6G dye onto PLA domains and higher binding affinity of Nile red toward PCL.