Background: Poly(d,l-lactide-co-glycolide) (PLGA) based biodegradable nanoparticles
are of key interest for the development of controlled release drug delivery systems and for other
biomedical applications. It has been reported that PLGA polymers can be converted into colloidal
nanoparticulate systems by various techniques, such as emulsification-diffusion, emulsificationevaporation,
interfacial deposition, salting out, dialysis and nanoprecipitation. Emulsificationevaporation
with water immiscible solvents including dichloromethane and chloroform has been the
preferred method for the synthesis of PLGA nanoparticles due to the low boiling point and limited
water solubility of these solvents. We and others, however, have found that when water-immiscible
solvents are used for the synthesis of PLGA nanoparticles, particle aggregation, non-uniform particle
size and multimodal size distribution are commonly encountered problems. This suggests that the
synthesis of PLGA nanoparticles using water immiscible solvents is highly sensitive to small procedural
variations that affect overall reproducibility.
Objective: This study presents a simple and robust procedure for the preparation of PLGA nanoparticles
with very small batch to batch variability (<5% variability in size (z-average) as determined by
dynamic light scattering).
Results: The results showed that the emulsification solvent diffusion method teamed with partially
water-miscible solvents, such as ethyl acetate, is a versatile approach for the preparation of PLGA
nanoparticles with highly reproducible sizes (between 50 and 400 nm) and zeta potentials (between -
30 and +30 mV), with relatively narrow polydispersity.
Conclusion: Emulsification-diffusion with ethyl acetate is, therefore, a more reliable alternative to
several existing procedures for the reproducible and refined synthesis of PLGA nanoparticles.