Influence of Albumin in the Microfluidic Synthesis of PEG-PLGA Nanoparticles

Abstract

Background: A key challenge in the manufacturing of polymeric colloids is producing nanoparticles with good batch-to-batch consistency.

Objective: Develop a robust microfluidics method for the preparation of PEG-PLGA nanoparticles using dimethyl sulfoxide (DMSO) as the organic phase solvent for the encapsulation of DMSO soluble agents.

Methods: Microfluidic process parameters, total flow rate (10 mL/min), flow rate ratio (1:1) of the aqueous phase and the organic polymer solution, and polymer concentration (5 mg/ml). Polyvinyl alcohol (PVA) or human serum albumin (HSA) was included in the aqueous phase. Dynamic light scattering and transmission electron microscopy were used to investigate the size and morphology of particles.

Results: PLGA nanoparticles made using DMSO with the aqueous solvent containing PVA (2%) had an average size of 60 nm while PLGA-PEG nanoparticles made with and without PVA (2%) had an average size of 70 and 100 nm, respectively. PLGA-PEG nanoparticles generated with or without PVA had a high batch-to-batch coefficient of variation for the particle size of 20% while for PLGA nanoparticles with PVA it was 4%. HSA added to the aqueous phase reduced the size and the zeta potential of PEG-PLGA nanoparticles as well the batch-to-batch coefficient of variation for particle size to < 5%. Nanoparticles were stable in solution and after lyophilized in the presence of sucrose.

Conclusion: Albumin was involved in the self-assembly of PEG-PLGA nanoparticles altering the physicochemical properties of nanoparticles. Adding protein to the aqueous phase in the microfluidic fabrication process may be a valuable tool for tuning the properties of nanoparticles and improving batch-to-batch consistency.

Keywords: Batch-to-batch reproducibility; PEG-PLGA; PEGylation; microfludics; nanoparticles; stability..