Self-Assembled Lipid Nanoparticles for Oral Delivery of Heparin-Coated Iron Oxide Nanoparticles for Theranostic Purposes.

Eleonora Truzzi,Elena Vismara,Eliana Leo,Francesca Sacchetti,Eleonora Maretti,Chiara Bongio,Monica Montanari,Valentina Iannuccelli

doi:10.3390/molecules22060963

Abstract

Recently, solid lipid nanoparticles (SLNs) have attracted increasing attention owing to their potential as an oral delivery system, promoting intestinal absorption in the lymphatic circulation which plays a role in disseminating metastatic cancer cells and infectious agents throughout the body. SLN features can be exploited for the oral delivery of theranostics. Therefore, the aim of this work was to design and characterise self-assembled lipid nanoparticles (SALNs) to encapsulate and stabilise iron oxide nanoparticles non-covalently coated with heparin (Fe@hepa) as a model of a theranostic tool. SALNs were characterised for physico-chemical properties (particle size, surface charge, encapsulation efficiency, in vitro stability, and heparin leakage), as well as in vitro cytotoxicity by methyl thiazole tetrazolium (MTT) assay and cell internalisation in CaCo-2, a cell line model used as an indirect indication of intestinal lymphatic absorption. SALNs of about 180 nm, which are stable in suspension and have a high encapsulation efficiency (>90%) were obtained. SALNs were able to stabilise the heparin coating of Fe@hepa, which are typically unstable in physiological environments. Moreover, SALNs–Fe@hepa showed no cytotoxicity, although their ability to be internalised into CaCo-2 cells was highlighted by confocal microscopy analysis. Therefore, the results indicated that SALNs can be considered as a promising tool to orally deliver theranostic Fe@hepa into the lymphatic circulation, although further in vivo studies are needed to comprehend further potential applications.

Highlights

Oral delivery is the most accepted route of drug administration, even though it is associated with poor drug bioavailability
Values were observed, regardless of the amount of Fe@hepa used, while the negative charge of the particle surface (Z-potential value) increased with the increase of the initial amount of Fe@hepa utilised in the preparation
The results indicate clearly that the loss of Fe@hepa was larger for the lower loaded sample (SALNs–Fe@hepa1)

Summary

Introduction

Oral delivery is the most accepted route of drug administration, even though it is associated with poor drug bioavailability. One of the most promising strategies to overcome these limitations is the use of nanomedicine or nano-drug delivery systems [1]. Solid lipid nanoparticles (SLNs) have attracted increasing attention owing to their biocompatibility and biodegradability. SLNs are composed of lipids in a solid state at room temperature and surfactants. They are produced using hot or cold homogenisation without the employment of organic solvents and generally have low production costs. SLNs offer advantages such as good tolerability, high oral drug

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