Formation of size-tuneable biodegradable polymeric nanoparticles by solvent displacement method using micro-engineered membranes fabricated by laser drilling and electroforming
journal contributionposted on 08.07.2016, 09:20 by Rahimah Othman, Goran Vladisavljevic, Hamed Shahmohamadi, Zoltan Nagy, Richard Holdich
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.
The authors acknowledge the financial support given for this work through the Ministry of Higher Education Malaysia and the technical assistance by Dr Zhaoxia Zhou and Dr Keith Yendall from the Department of Materials at Loughborough University for TEM and FEG-SEM analyses. The authors also acknowledge the financial support provided by the EPSRC grant EP/HO29923/1 and the European Research Council grant [280106-CrySys].
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- Chemical Engineering