Abstract

We present an experimental study of self-assembled polymeric nanoparticles in the process of flash nanoprecipitation using a multi-inlet vortex mixer (MIVM). β-Carotene and polyethyleneimine (PEI) are used as a model drug and a macromolecule, respectively, and encapsulated in diblock copolymers. Flow patterns in the MIVM are microscopically visualized by mixing iron nitrate (Fe(NO3)3) and potassium thiocyanate (KSCN) to precipitate Fe(SCN) (3−)+ . Effects of physical parameters, including Reynolds number, supersaturation rate, interaction force, and drug-loading rate, on size distribution of the nanoparticle suspensions are investigated. It is critical for the nanoprecipitation process to have a short mixing time, so that the solvent replacement starts homogeneously in the reactor. The properties of the nanoparticles depend on the competitive kinetics of polymer aggregation and organic solute nucleation and growth. We report the existence of a threshold Reynolds number over which nanoparticle sizes become independent of mixing. A similar value of the threshold Reynolds number is confirmed by independent measurements of particle size, flow-pattern visualization, and our previous numerical simulation along with experimental study of competitive reactions in the MIVM.

Highlights

  • Nanoparticles have recently been the focus of much attention because of their broad biomedical applications in small molecule drug delivery (Cho et al 2008; Johnson and Prud'homme 2003b; Liong et al 2008), gene and protein delivery (Li et al 2008; Ayame et al 2008; Sun et al 2008), medical imaging and diagnosis (Hainfeld et al 2006; Xie et al 2009), and photothermal therapy (Huang et al 2006)

  • Flash NanoPrecipitation is a process of kinetic control instead of thermodynamic equilibrium which constrains the drug loading rate and causes broad size distribution and low stability as in most other processes, such as emulsion and traditional precipitation

  • High Reynolds number homogenous mixing was essential to start the competitive processes of organic solute nucleation and growth as well as polymer aggregation simultaneously and uniformly, which provided control over drug loading rate and uniform particle size distribution

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Summary

Introduction

Nanoparticles have recently been the focus of much attention because of their broad biomedical applications in small molecule drug delivery (Cho et al 2008; Johnson and Prud'homme 2003b; Liong et al 2008), gene and protein delivery (Li et al 2008; Ayame et al 2008; Sun et al 2008), medical imaging and diagnosis (Hainfeld et al 2006; Xie et al 2009), and photothermal therapy (Huang et al 2006). Short mixing time ensures the solvent replacement starts homogeneously, so that the properties of the nanoparticles depend on the competitive kinetics of polymer aggregation and organic solute nucleation and growth. The dependence of the nanoparticle sizes on Reynolds number, supersaturation rate, nature of polymers, drug loading rate, and the type of interaction forces was studied.

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