Controlled and tunable polymer particles\u2019 production using a single microfluidic device

Benzion Amoyav,Ofra Benny

doi:10.1007/s13204-018-0790-0

Abstract

Microfluidics technology offers a new platform to control liquids under flow in small volumes. The advantage of using small-scale reactions for droplet generation along with the capacity to control the preparation parameters, making microfluidic chips an attractive technology for optimizing encapsulation formulations. However, one of the drawback in this methodology is the ability to obtain a wide range of droplet sizes, from sub-micron to microns using a single chip design. In fact, typically, droplet chips are used for micron-dimension particles, while nanoparticles’ synthesis requires complex chips design (i.e., microreactors and staggered herringbone micromixer). Here, we introduce the development of a highly tunable and controlled encapsulation technique, using two polymer compositions, for generating particles ranging from microns to nano-size using the same simple single microfluidic chip design. Poly(lactic-co-glycolic acid) (PLGA 50:50) or PLGA/polyethylene glycol polymeric particles were prepared with focused-flow chip, yielding monodisperse particle batches. We show that by varying flow rate, solvent, surfactant and polymer composition, we were able to optimize particles’ size and decrease polydispersity index, using simple chip designs with no further related adjustments or costs. Utilizing this platform, which offers tight tuning of particle properties, could offer an important tool for formulation development and can potentially pave the way towards a better precision nanomedicine.

Highlights

The synthesis of well-defined monodisperse polymeric drug particles is a central challenge in the development of drug delivery systems, especially for injectable products
We prove that the choice of polymers and solvents is the main key factors in the production of polymeric particles using microfluidic devices
The dispersive phase rate remained constant with 0.05 ml/min, while the continuous flow rate was set to either 0.4, 0.5, 0.6, 0.8, and 1 ml/min

Summary

Introduction

The synthesis of well-defined monodisperse polymeric drug particles is a central challenge in the development of drug delivery systems, especially for injectable products. Downscaling processes with a microfluidic device offer many advantages including the low cost and faster parallel analysis for formulation development using many various conditions in a single chip (Novotný and Foret 2017; Valencia et al 2012). The particle size of polymer carriers is one of the key parameters that govern the bio-distribution of the product, and is critical for bioavailability of drugs (Banerjee et al 2016; Kumar et al 2015; Yin; Win and Feng 2005). A great effort has been invested in learning to control the fabrication process, mainly of degradable polymer particles, to produce particles with distinct and defined size.

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