Overcoming the Limits of Flash Nanoprecipitation: Effective Loading of Hydrophilic Drug into Polymeric Nanoparticles with Controlled Structure.

Daniele Massella,Edvige Celasco,Ada Ferri,Fabien Salaün,Antonello Barresi

doi:10.3390/polym10101092

Abstract

Flash nanoprecipitation (FNP) is a widely used technique to prepare particulate carriers based on various polymers, and it was proven to be a promising technology for the industrial production of drug loaded nanoparticles. However, up to now, only its application to hydrophobic compounds has been deeply studied and the encapsulation of some strongly hydrophilic compounds, such as caffeine, remains a challenge. Caffeine loaded poly-ε-caprolactone (PCL) nanoparticles were produced in a confined impinging jet mixer using acetone as the solvent and water as the antisolvent. Caffeine was dissolved either in acetone or in water to assess the effects of two different process conditions. Nanoparticles properties were assessed in terms of loading capacity (LC%), encapsulation efficiency (EE%), and in vitro release kinetics. Samples were further characterized by dynamic light scattering, scanning electron microscopy, X-ray photo electron spectroscopy, and infrared spectroscopy to determine the size, morphology, and structure of nanoparticles. FNP was proved an effective technique for entrapping caffeine in PCL and to control its release behavior. The solvent used to solubilize caffeine influences the final structure of the obtained particles. It was observed that the active principle was preferentially adsorbed at the surface when using acetone, while with water, it was embedded in the matrix structure. The present research highlights the possibility of extending the range of applications of FNP to hydrophilic molecules.

Highlights

The production of nanocarriers is one the most innovative and promising research fields in modern pharmaceutical technology: As a matter of fact, the use of nanoscale formulations can improve drug compatibility [1,2], provide more accurate diagnosis [3,4], reduce the risk of immune response [5,6], and achieve targeted drug delivery [7,8]
The method proposed by Allen [27] greatly expanded the capabilities of flash nanoprecipitation (FNP) by simultaneously loading hydrophilic and hydrophobic substances, as hydrophilic compounds tend to interact with the nanocarriers’ surface; with strongly hydrophilic substances, the maximum achieved EE% was lower than 20%
loading capacity (LC) is defined as the mass of the encapsulated drug divided by the mass of the whole polymeric nanoparticles system, as given by Equation (1); it is an index of the amount of drug that can be incorporated in a given amount of nanoparticle formulation

Summary

Introduction

The production of nanocarriers is one the most innovative and promising research fields in modern pharmaceutical technology: As a matter of fact, the use of nanoscale formulations can improve drug compatibility [1,2], provide more accurate diagnosis [3,4], reduce the risk of immune response [5,6], and achieve targeted drug delivery [7,8]. The governing factor in the nanoparticle formation is mixing [12]; special micro-mixers have been designed and tested to effectively control mixing efficiency [13] Among these devices, the confined impinging jet mixer (CIJM) has been widely used in several experimental works [14,15]. The flash nanoprecipitation technique has been mainly used to entrap highly hydrophobic drugs (logP > 3.5) to achieve encapsulation efficiencies close to 100%. Such high yields are due to the scarce affinity of hydrophobic drugs with water and the concurrent precipitation of the drug and polymer upon jet collision [21,22,23]. Caffeine was selected for encapsulation in PCL nanoparticles via FNP to prove the limit of this technique and obtain insight into the mechanisms of partitioning the hydrophilic drug between the polymer and the liquor

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