Preparation of biodegradable polymeric nanoparticles for pharmaceutical applications using glass capillary microfluidics

The aim of this study was to develop a new microfluidic approach for the preparation of nanoparticles with tuneable sizes based on micromixing/direct nanoprecipitation in a coaxial assembly of tapered-end glass capillaries. The organic phase was 1 wt% poly(ε-caprolactone) (PCL) or poly(dl-lactic acid) (PLA) in tetrahydrofuran and the antisolvent was Milli-Q water. The size of nanoparticles was precisely controlled over a range of 190–650 nm by controlling phase flow rates, orifice size and flow configuration (two-phase co-flow or counter-current flow focusing). Smaller particles were produced in a flow focusing device, because the organic phase stream was significantly narrower than the orifice and remained narrow for a longer distance downstream of the orifice. The mean size of PCL particles produced in a flow focusing device with an orifice size of 200 μm, an organic phase flow rate of 1.7 mL h−1 and an aqueous-to-organic flow rate ratio of 10 was below 200 nm. The size of nanoparticles decreased with decreasing the orifice size and increasing the aqueous-to-organic phase flow rate ratio. Due to higher affinity for water and amorphous structure, PLA nanoparticles were smaller and exhibited a smoother surface and more rounded shape than PCL particles.