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

Abstract

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 2 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 4-30 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 modelling results using the volume of fluid-continuum surface force model agreed well with experimental behaviour 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.

Microencapsulation of Clostridium difficile specific bacteriophages using microfluidic glass capillary devices for colon delivery using pH triggered release

“…This was done in real-time whilst observing (using the microscope camera) the change in the resulting droplet size. When increasing the flow rate of the inner phase relative to the outer phase, the size of the droplets increased; this trend was well documented and observed in many experimental and numerical studies [55]. Typically, the following relationship exists between the drop diameter, d drop , the orifice diameter, d orifice , and the flow rate ratio [56]: d drop / d orifice ∝ (Q c / Q d ) − x , where x is about 0.4.…”

“…The dripping regime occurs when the Weber number of the dispersed phase and the Capillary number of the continuous phase are both below their critical values. The Capillary number ( Ca ) represents the ratio between the viscous forces and interfacial tension across an interface between the two phases [52], [53], [55]. The Capillary number of the continuous phase is given by: Ca c = μ c V c / γ , where μ c is the dynamic viscosity of the continuous phase, and V c is the mean velocity of the continuous phase.…”

Effective interfacial tension in flow-focusing of colloidal dispersions: 3-D numerical simulations and experiments

“…Microfluidic techniques have facilitated the development of both fundamental and applied research in the field of chemistry, biology, medicine, material and physical sciences (Squires & Quake 2005;Whitesides 2006;Stone et al 2004;Nunes et al 2013). In particular, the flow-focusing configuration (illustrated in figure 1), where a core fluid is focused by two sheath flows has been successfully employed in a wide variety of applications such as bubble or droplet formation (Cubaud & Mason 2008;Anna et al 2003;Garstecki et al 2004), micro and nano-particle production (Martín-Banderas et al 2005), hydrodynamic assembly of nanoparticle dispersion into high-performance superstructures (Håkansson et al 2014;Ekanem et al 2015;Kamada et al 2017;Mittal et al 2018), cell patterning (Takayama et al 1999), DNA stretching (Wong et al 2003), and diffusion-mixers (Knight 1998;Pollack et al 1999). At the micrometre scale, phenomena such as interfacial tension and viscosity usually become dominant compared to the effects of gravity and inertia, which often are negligible.…”

Janus particles: from concepts to environmentally friendly materials and sustainable applications

“…Droplet-based microfluidic processes for the fabrication of anisotropic microgels have been accomplished using w/o emulsion droplets combined with UV-induced polymerization or ionic crosslinking to solidify the Janus droplets (on-chip or offchip) [28]. The design of the fabrication process broadly varies from (double) T-junction microfluidic devices [27,36,58], stop-flow lithography microfluidic techniques [59,60], flow-focusing microfluidic devices [30,33,38,44,61], double emulsion droplet templates [62], and single emulsion/offchip cross-linking [28]. Using this technique, magnetic and/or fluorescent components can be easily embedded in one compartment of the JPs [27,30,34,36].…”