Structured
Biodegradable Polymeric Microparticles for Drug Delivery Produced
Using Flow Focusing Glass Microfluidic Devices
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Abstract
Biodegradable poly(dl-lactic
acid) (PLA) and poly(lactic-<i>co</i>-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
