Formation of size-tuneable biodegradable polymeric nanoparticles by solvent displacement method using micro-engineered membranes fabricated by laser drilling and electroforming

Biodegradable poly(ε-caprolactone) (PCL) drug-carrier nanoparticles (NPs) were produced by rapid membrane micromixing combined with nanoprecipitation in a stirred cell employing novel membrane dispersion. The organic phase composed of 0.1−0.6 wt% PCL dissolved in tetrahydrofuran was injected into the aqueous phase (Mili-Q water or 0.2−1 wt% poly(vinyl alcohol) using two microfabricated membranes with different pore morphologies and spatial pore arrangements: ringed stainless steel membrane of reduced (annular) operating area with a square array of cylindrical laser-drilled pores and electroformed nickel membrane of full operating area with a hexagonal array of conical, funnel-shaped pores. The size of the NPs was precisely controlled over a range of 159−394 nm by changing the aqueous-to-organic volumetric ratio, stirring rate, transmembrane flux, the polymer content in the organic phase, membrane type and pore size. The smallest and most uniform particles with a Z-average of 159 nm and a polydispersity index of 0.107±0.014 were obtained using a 10 μm pore-sized stainless steel membrane at the transmembrane flux of 140 L m-2 h-1, a stirring rate of 1,300 rpm, and an aqueous-to-organic phase volume ratio of 10 using 1 g L-1 PCL in the organic phase. The particle size decreased by increasing the stirring rate and the aqueous-to-organic volumetric ratio, and by decreasing the polymer concentration in the aqueous phase and the transmembrane flux. The existence of the peak shear stress within a transitional radius and a rapid decline of the shear stress away from the membrane surface were revealed by numerical modelling.