Fabrication of monodisperse poly(dl- lactic acid) microparticles using drop microfluidics

Monodisperse poly(dl-lactic acid) particles with a diameter between 11 and 121 μm were fabricated by drop microfluidics/solvent evaporation method using flow focusing glass capillary device. In the dripping regime, the ratio of droplet diameter to orifice diameter was in the range of 0.37−1.34 and was inversely proportional to the 0.39 power of the ratio of the continuous phase flow rate to dispersed phase flow rate

Emulsion templating of poly(lactic acid) particles: droplet formation behavior

Monodisperse poly(dl-lactic acid) (PLA) particles of diameters between 11 and 121 ?m were fabricated in flow focusing glass microcapillary devices by evaporation of dichloromethane (DCM) from emulsion droplets at room temperature. The dispersed phase was 5% (w/w) PLA in DCM containing 0.1−2 mM Nile red and the continuous phase was 5% (w/w) poly(vinyl alcohol) in reverse osmosis water. Particle diameter was 2.7 times smaller than the diameter of the emulsion droplet template indicating very low particle porosity. Monodisperse droplets have only been produced under dripping regime using a wide range of dispersed phase flow rates (0.002−7.2 cm3h-1), continuous phase flow rates (0.3−30 cm3h-1) and orifice diameters (50−237 ?m). In the dripping regime, the ratio of droplet diameter to orifice diameter was inversely proportional to the 0.39 power of the ratio of the continuous phase flow rate to dispersed phase flow rate. Highly uniform droplets with a coefficient of variation (CV) below 2 % and a ratio of the droplet diameter to orifice diameter of 0.5−1 were obtained at flow rate ratios of 4−25. Under jetting regime, polydisperse droplets (CV > 6 %) were formed by detachment from relatively long jets (between 4 and 10 times longer than droplet diameter) and a ratio of the droplet size to orifice size was 2−5

Fabrication of biodegradable poly(lactic acid) particles in flow focusing glass capillary devices

Fabrication of biodegradable poly(lactic acid) particles in flow focusing glass capillary device

Fabrication of biodegradable poly(lactic acid) particles in flow-focusing glass capillary devices

Monodisperse poly(dl-lactic acid) (PLA) particles with a diameter in the range from 12 to 100 9m were fabricated in flow focusing glass capillary devices by evaporation of dichloromethane (DCM) from emulsions at room temperature. The dispersed phase was 5% (w/w) PLA in DCM containing a small amount of Nile red and the continuous phase was 5% (w/w) poly(vinyl alcohol) in reverse osmosis water. Particle diameter was 2.7 times smaller than the size of the emulsion droplet template indicating that the particle porosity was very low. SEM images revealed that the majority of particle pores are in the sub-micron region but in some instances these pores can reach 3 9m in diameter. Droplet diameter was influenced by the flow rates of the two phases and the entry diameter of the collection capillary tube; droplet diameters decreased with increasing values of the flow rate ratio of the dispersed to continuous phase to reach constant minimum values at 40-60 % orifice diameter. At flow rate ratios less than 5, jetting can occur, giving rise to large droplets formed by detachment from relatively long jets (~10 times longer than droplet diameter)

Monodisperse w/w/w Double Emulsion Induced by Phase Separation

We develop an approach to fabricate monodisperse water-in-water-in-water (w/w/w) double emulsion in microfluidic devices. A jet of aqueous solution containing two incompatible solutes, dextran and polyethylene glycol (PEG), is periodically perturbed into water-in-water (w/w) droplets. By extracting water out of the w/w droplet, the solute concentrations in the droplet phase increase; when the concentrations exceed the miscibility limit, the droplet phase separates into two immiscible phases. Consequently, PEG-rich droplets are formed within the single emulsion templates. These PEG-rich droplets subsequently coalesce with each other, resulting in transiently stable w/w/w double emulsions with a high degree of size uniformity. These double emulsions are free of organic solvents and thus are ideal for use as droplet-vessels in protein purification, as microreactors for biochemical reactions, and as templates for fabrication of biomaterials

Monodisperse w/w/w Double Emulsion Induced by Phase Separation

We develop an approach to fabricate monodisperse water-in-water-in-water (w/w/w) double emulsion in microfluidic devices. A jet of aqueous solution containing two incompatible solutes, dextran and polyethylene glycol (PEG), is periodically perturbed into water-in-water (w/w) droplets. By extracting water out of the w/w droplet, the solute concentrations in the droplet phase increase; when the concentrations exceed the miscibility limit, the droplet phase separates into two immiscible phases. Consequently, PEG-rich droplets are formed within the single emulsion templates. These PEG-rich droplets subsequently coalesce with each other, resulting in transiently stable w/w/w double emulsions with a high degree of size uniformity. These double emulsions are free of organic solvents and thus are ideal for use as droplet-vessels in protein purification, as microreactors for biochemical reactions, and as templates for fabrication of biomaterials

Hypromellose-<i>graft</i>-chitosan and Its Polyelectrolyte Complex as Novel Systems for Sustained Drug Delivery

Polyelectrolyte complexes formed between chitosan (CS) and anionic polymers have attracted increasing interest in drug delivery. In this study, CS is copolymerized with hypromellose via a coupling reagent-mediated approach to form a water-soluble, nontoxic CS derivative, namely hypromellose-<i>graft</i>-CS (HC), which is subsequently complexed with carboxymethylcellulose (CMC) to generate a polyampholytic hydrogel. When compared with conventional CS, HC is highly water-soluble across a wide pH range, and has a substantially higher pH buffering capacity to provide a pH-stable environment for delivery of drugs. In addition, the polyelectrolyte complex of HC exhibits a drug encapsulation efficiency of over 90% in all drugs tested, which is 1–2 fold higher than the efficiency attainable by the polyelectrolyte complex of conventional CS, with a 2–3 fold longer duration of sustained drug release. Our results indicate that as a novel polymer, HC has excellent promise for future pharmaceutical applications

Control over the shell thickness of core/shell drops in three-phase glass capillary devices

Monodisperse core/shell drops with aqueous core and poly(dimethylsiloxane) (PDMS) shell of controllable thickness have been produced using a glass microcapillary device that combines co-flow and flow-focusing geometries. The throughput of the droplet generation was high, with droplet generation frequency in the range from 1,000 to 10,000 Hz. The size of the droplets can be tuned by changing the flow rate of the continuous phase. The technique enables control over the shell thickness through adjusting the flow rate ratio of the middle to inner phase. As the flow rate of the middle and inner phase increases, the droplet breakup occurs in the dripping-to-jetting transition regime, with each double emulsion droplet containing two monodisperse internal aqueous droplets. The resultant drops can be used subsequently as templates for monodisperse polymer capsules with a single or multiple inner compartments, as well as functional vesicles such as liposomes, polymersomes and colloidosomes

Control over the shell thickness of core/shell drops in three-phase glass capillary devices

Control over the shell thickness of core/shell drops in three-phase glass capillary device

Control over the shell thickness of core/shell drops in three-phase glass capillary devices

Monodisperse core/shell drops with aqueous core and poly(dimethylsiloxane) (PDMS) shell of controllable thickness have been produced using a glass microcapillary device that combines co-flow and flow-focusing geometries. The throughput of the droplet generation was high, with droplet generation frequency in the range from 1,000 to 10,000 Hz. The size of the droplets can be tuned by changing the flow rate of the continuous phase. The technique enables control over the shell thickness through adjusting the flow rate ratio of the middle to inner phase. As the flow rate of the middle and inner phase increases, the droplet breakup occurs in the dripping-to-jetting transition regime, with each double emulsion droplet containing two monodisperse internal aqueous droplets. The resultant drops can be used subsequently as templates for monodisperse polymer capsules with a single or multiple inner compartments, as well as functional vesicles such as liposomes, polymersomes and colloidosomes