Stealth Behavior of Poly(ethyloxazoline)s-Modified Hydroxyethyl Starch-Based Nanocapsules

Abstract

Poly(oxazoline)s (POZs) are a “new” class of biocompatible polymers that show unique and specific properties for modern biomedical and biomaterials design applications. In this work, POZs-coupled hydroxyethyl starch nanocapsules were developed in order to create a powerful protein suppressor vehicle. Herein, POZs of different molecular weights were used to functionalize the well-known hydroxyethyl starch nanocapsules (HES) surface by metal-free “click” chemistry, in which HES have also been related to immune suppressor property. For each modification step, the capsules were characterized regarding size, morphology and charge surface, and, as expected, the “click” strategy kept a core-shell structure with an average diameter distribution < 200 nm. Additionally, previous to the post-polymerization modification step, the amount of free amino groups was determined by fluorescence intensity, allowing further “click” coupling of the surface of the capsules with POZs, later confirmed by gel permeation chromatography. Protein corona evaluation and aggregation assays in human plasma showed lower protein attaching for POZ-modified HES nanocapsules, than HES modified with polyethylene glycol (“PEGylated”-HES) and unmodified HES. Indeed, around 35% of “hard” protein corona of POZ-modified HES are clusterins, the apolipoprotein that can reduce the nonspecific cellular uptake into macrophages, indicating that POZs have stealth behavior similar to polyethylene glycol (PEG), being a potential alternative to “PEGylated”-based nanocarriers.