Controlling Nanoparticle Formulation: A Low-Budget Prototype for the Automation of a Microfluidic Platform

Dominik M Loy,Ulrich Lächelt,Ernst Wagner,Rafał Krzysztoń,Joachim O Rädler

doi:10.3390/pr9010129

Abstract

Active pharmaceutical ingredients (API) with suboptimal pharmacokinetic properties may require formulation into nanoparticles. In addition to the quality of the excipients, production parameters are crucial for producing nanoparticles which reliably deliver APIs to their target. Microfluidic platforms promise increased control over the formulation process due to the decreased degrees of freedom at the micro- and nanoscale. Publications about these platforms usually provide only limited information about the soft- and hardware required to integrate the microfluidic chip seamlessly into an experimental set-up. We describe a modular, low-budget prototype for microfluidic mixing in detail. The prototype consists of four modules. The control module is a raspberry pi executing customizable python scripts to control the syringe pumps and the fraction collector. The feeding module consists of up to three commercially available, programable syringe pumps. The formulation module can be any macro- or microfluidic chip connectable to syringe pumps. The collection module is a custom-built fraction collector. We describe each feature of the working prototype and demonstrate its power with polyplexes formulated from siRNA and two different oligomers that are fed to the chip at two different stages during the assembly of the nanoparticles.

Highlights

Packaging active pharmaceutical ingredients (API) into nanoparticles can alter the pharmacokinetic properties of drugs fundamentally [1,2,3]
We describe each feature of the working prototype and demonstrate its power with polyplexes formulated from siRNA and two different oligomers that are fed to the chip at two different stages during the assembly of the nanoparticles
The control module is a remotely accessible raspberry pi which controls the syringe pumps via a Recommended Standard 232 (RS232) interface and the fraction collector via the generalpurpose input/output (GPIO) pins

Summary

Introduction

Packaging active pharmaceutical ingredients (API) into nanoparticles can alter the pharmacokinetic properties of drugs fundamentally [1,2,3]. It is a well-established strategy to improve the biodistribution of small molecule drugs like paclitaxel [4] as well as larger, oligomeric drugs like nucleic acids [5,6]. Mixing cationic oligo- or polymeric excipients with negatively charged nucleic acids to induce nanoparticle formation, for example, is an established method from the bottom-up approach [13]. These nanoparticles are named polyplexes [14]. The properties of polyplexes and their effectiveness is determined by their individual components and the formulation process parameters [15]

Methods

Results

Conclusion