Abstract

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.

Original languageEnglish
Article number134885
Number of pages7
JournalColloids and Surfaces A: Physicochemical and Engineering Aspects
Volume701
DOIs
Publication statusPublished - 20 Nov 2024

Bibliographical note

Publisher Copyright:
© 2024 The Authors

Keywords

  • Drug delivery
  • Dynamic solvent extraction
  • Ethyl acetate
  • Microfluidics
  • Microparticle
  • PLGA
  • Shrinkage rate

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