Coupled Hydrodynamic Flow Focusing (cHFF) to Engineer Lipid-Polymer Nanoparticles (LiPoNs) for Multimodal Imaging and Theranostic Applications.

Felicia Roffo,Paolo Antonio Netti,Alfonso Maria Ponsiglione,Enza Torino

doi:10.3390/biomedicines10020438

Abstract

An optimal design of nanocarriers is required to overcome the gap between synthetic and biological identity, improving the clinical translation of nanomedicine. A new generation of hybrid vehicles based on lipid–polymer coupling, obtained by Microfluidics, is proposed and validated for theranostics and multimodal imaging applications. A coupled Hydrodynamic Flow Focusing (cHFF) is exploited to control the time scales of solvent exchange and the coupling of the polymer nanoprecipitation with the lipid self-assembly simultaneously, guiding the formation of Lipid–Polymer NPs (LiPoNs). This hybrid lipid–polymeric tool is made up of core–shell structure, where a polymeric chitosan core is enveloped in a lipid bilayer, capable of co-encapsulating simultaneously Gd-DTPA and Irinotecan/Atto 633 compounds. As a result, a monodisperse population of hybrid NPs with an average size of 77 nm, with preserved structural integrity in different environmental conditions and high biocompatibility, can be used for MRI and Optical applications. Furthermore, preliminary results show the enhanced delivery and therapeutic efficacy of Irinotecan-loaded hybrid formulation against U87 MG cancers cells.

Highlights

A wide range of continuous microfluidic processes has been implemented for functional material synthesis [1,2] to take advantage of microfluidic peculiarity
We addressed Gadolinium-based Contrast agents (CAs) for Magnetic Resonance Imaging (MRI) because, even though MRI represents the most clinically applied modality [27], Gadolinium-free CAs still suffer from transmetalation, nephrotoxic effects and abnormal brain deposition [28,29,30]
We presented a new generation of lipid polymer nanoparticles obtained by coupled Hydrodynamic Flow Focusing, modifying HFF and using it in an innovative manner to control the coupling of the lipid fragments with the polymer nuclei

Summary

Introduction

A wide range of continuous microfluidic processes has been implemented for functional material synthesis [1,2] to take advantage of microfluidic peculiarity. Hydrodynamic Flow Focusing (HFF), in the forms of emulsion and solvent extraction, has been widely exploited to produce micro- and nanoparticles [3]. Jahn and co-workers [8] synthesised liposomes in a microfluidic Y-shaped device where a lipid stream is hydrodynamically sheathed between two oblique buffer streams. The microfluidic ability to promote the ordered interaction among lipid and polymer materials was exploited to produce hybrid architectures [9], which depending on component configurations, are classified as lipid–polymer or polymer–lipid architectures [10]. The lipid–polymer architectures combine the biodegradable core of polymer with the lipid-layer or bilayer, analogues of biological membranes, enhancing the encapsulation efficacy and offering superior biocompatibility [11] and cell

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