TY - JOUR
T1 - Advanced microfluidic techniques for in situ PLGA microparticle formation
T2 - A dynamic solvent extraction approach
AU - Amanatchi, Nader
AU - Bihi, Ilyesse
AU - Briet, Matthieu
AU - Stichelmans, Jordy
AU - Malsche, Wim De
AU - Hellemans, Karine H.
N1 - Publisher Copyright:
© 2024 The Authors
PY - 2024/11/20
Y1 - 2024/11/20
N2 - Microencapsulation processes often use the “solvent extraction/evaporation” technique, which involves (i) dissolving a polymer in an organic solvent (optionally with a bioactive component), (ii) forming microdroplets, (iii) removing the solvent, and finally (iv) harvesting and drying the particles ex situ. These last two steps lack control over the solidification processes, which adversely affects the morphology and size distribution of the final microparticles. In this study, we present a continuous production process for solid PLGA microparticles within a microfluidic chip, covering droplet formation, solvent extraction, and solidification. This method offers the advantage of enhanced control over the solidification process within a closed system, leading to morphologically uniform particles. The setup includes a co-axial junction integrated into a chip with an 80 cm long serpentine channel. We generated droplets with various PLGA/ethyl acetate concentrations and tracked their shrinkage until solidification. Results showed that all droplets underwent identical shrinkage processes with consistent rates, velocity profiles, and sizes. The shrinkage rate was linear and unaffected by PLGA concentration, which only influenced final particle size. To demonstrate our setup's advantages, we compared it with the conventional off-chip method, where droplets shrink in a beaker. Off-chip shrinkage was non-linear and inconsistent, influenced by factors such as the number of surrounding droplets and production time. Droplets produced within a 10-s difference had solidification delays up to 250 s. In contrast, on-chip production was uniform, predictable, and 4–10 times faster. SEM imaging confirmed that on-chip particles were consistently spherical with a rough, wrinkled surface, unlike the irregular, bumpy off-chip particles. In summary, on-chip production and shrinkage of PLGA particles is faster and produces more uniformly shaped particles compared to off-chip methods. This study suggests that on-chip production could significantly enhance the efficiency and quality of drug-loaded microparticles, particularly for drug delivery applications.
AB - Microencapsulation processes often use the “solvent extraction/evaporation” technique, which involves (i) dissolving a polymer in an organic solvent (optionally with a bioactive component), (ii) forming microdroplets, (iii) removing the solvent, and finally (iv) harvesting and drying the particles ex situ. These last two steps lack control over the solidification processes, which adversely affects the morphology and size distribution of the final microparticles. In this study, we present a continuous production process for solid PLGA microparticles within a microfluidic chip, covering droplet formation, solvent extraction, and solidification. This method offers the advantage of enhanced control over the solidification process within a closed system, leading to morphologically uniform particles. The setup includes a co-axial junction integrated into a chip with an 80 cm long serpentine channel. We generated droplets with various PLGA/ethyl acetate concentrations and tracked their shrinkage until solidification. Results showed that all droplets underwent identical shrinkage processes with consistent rates, velocity profiles, and sizes. The shrinkage rate was linear and unaffected by PLGA concentration, which only influenced final particle size. To demonstrate our setup's advantages, we compared it with the conventional off-chip method, where droplets shrink in a beaker. Off-chip shrinkage was non-linear and inconsistent, influenced by factors such as the number of surrounding droplets and production time. Droplets produced within a 10-s difference had solidification delays up to 250 s. In contrast, on-chip production was uniform, predictable, and 4–10 times faster. SEM imaging confirmed that on-chip particles were consistently spherical with a rough, wrinkled surface, unlike the irregular, bumpy off-chip particles. In summary, on-chip production and shrinkage of PLGA particles is faster and produces more uniformly shaped particles compared to off-chip methods. This study suggests that on-chip production could significantly enhance the efficiency and quality of drug-loaded microparticles, particularly for drug delivery applications.
KW - Drug delivery
KW - Dynamic solvent extraction
KW - Ethyl acetate
KW - Microfluidics
KW - Microparticle
KW - PLGA
KW - Shrinkage rate
UR - http://www.scopus.com/inward/record.url?scp=85199361277&partnerID=8YFLogxK
U2 - 10.1016/j.colsurfa.2024.134885
DO - 10.1016/j.colsurfa.2024.134885
M3 - Article
AN - SCOPUS:85199361277
VL - 701
JO - Colloids and Surfaces A Physicochemical and Engineering Aspects
JF - Colloids and Surfaces A Physicochemical and Engineering Aspects
SN - 0927-7757
M1 - 134885
ER -