Mass Production and Size Control of Lipid–Polymer Hybrid Nanoparticles through Controlled Microvortices

Abstract

Lipid-polymer hybrid (LPH) nanoparticles can deliver a wide range of therapeutic compounds in a controlled manner. LPH nanoparticle syntheses using microfluidics improve the mixing process, but are restricted by a low throughput. In this study we present a pattern-tunable microvortex platform that allows mass production and size control of LPH nanoparticles with superior reproducibility and homogeneity. We demonstrate that by varying flow rates (i.e. Reynolds number (30∼150)) we can control the nanoparticle size (30∼170nm) with high productivity (∼3g/hour) and low polydispersity (∼0.1). Our approach may contribute to efficient development and optimization of a wide range of multicomponent nanoparticles for medical imaging and drug delivery.

Lipid-Based Drug Delivery Systems in Cancer Therapy: What Is Available and What Is Yet to Come

“…In a study by Kim et al (2012), the microchannel apparatus used for preparing LPNs (Valencia et al, 2010) was improved upon by using a three-inlet setup. This consisted of the organic phase going through the central inlet, while the aqueous phase was injected through two inlets on either side (Kim et al, 2012).…”

“…This consisted of the organic phase going through the central inlet, while the aqueous phase was injected through two inlets on either side (Kim et al, 2012). This setup enabled a three-dimensional flow to generate a symmetrical microvortex, which led to the dispersion of large aggregates into smaller particles, resulting in a 200-fold improvement in LPN throughput compared with the original method (Valencia et al, 2010;Kim et al, 2012). A larger-scale microfluidic 770 nanoprecipitation process using a multi-inlet vortex reactor with four radially symmetrical inlets was also developed recently by Fang et al (2012).…”

Multiphase microfluidic synthesis of micro- and nanostructures for pharmaceutical applications

“…To achieve the high-throughput synthesis of LPNs, a microfluidic device was designed to operate at high Reynold numbers (up to 150) using controlled microvortices. It can achieve a production rate of 3 g/h, which was 1000 times higher than the diffusion mixing in a microfluidic flow-focusing pattern and 200 times faster than convective mixing in a Tesla-type mixer (Kim et al, 2012). .…”

Fundamental studies on throughput capacities of hydrodynamic flow-focusing microfluidics for producing monodisperse polymer nanoparticles

“…Several groups had worked on different designs with the aim to improve the yield (Kang et al, 2013, Kim et al, 2012, Min et al, 2014and Lim et al, 2014. Microfluidic parallelization was a strategy to achieve clinically relevant production rates but the manual drilling and punching which was required in the fabrication process provided limited accuracy and repeatability between devices (Romanowsky et al, 2012).…”