The different ways to chitosan/hyaluronic acid nanoparticles: templated vs. direct complexation. Influence of particle preparative processes on morphology, cell uptake and silencing efficiency

Arianna Gennari, Julio M. Rios de la Rosa, Erwin Hohn, Maria Pelliccia, Enrique Lallana, Roberto Donno, Annalisa Tirella, Nicola Tirelli

Research output: Contribution to journalArticlepeer-review

Abstract

This study is about linking preparative processes of nanoparticles, their morphology and their efficiency in intracellular delivery. The nanoparticles are composed of hyaluronic acid (HA) and chitosan; the former can address a nanoparticle to cell surface receptors such as CD44, the second allows both for entrapment of nucleic acids and for an endosomolytic activity that facilitates their liberation in the cytoplasm. Here, we have systematically compared nanoparticles prepared A) through a 2-step process, based on intermediate (template) particles produced via ionotropic gelation with triphosphate (TPP), which are then incubated with HA, B) through direct polyelectrolyte complexation of chitosan and HA. Here we demonstrate that HA is capable to quantitatively replace TPP in the template process and during the TPP-HA exchange significant aggregation takes place. The templated chitosan/HA nanoparticle threfore have a mildly larger size (by stand-alone dynamic light scattering or by field flow fractionation coupled to static or dynamic light scattering), and above all a higher aspect ratio (Rg/RH) and la ower fractal dimension. We then compared the kinetics of uptake and the (anti-luciferase) siRNA delivery performance on murine RAW 264.7 macrophages and on human HCT-116 colorectal tumor cells. In these studies the preparative method (and therefore of the internal particle morphology) had little effect on the uptake kinetics and a statistically irrelevant one on silencing (templated particles often showing a lower silencing). Cell-specific factors, on the contrary, overwhelmingly determined the efficacy of the carriers, with e.g. those containing low MW chitosan performing better in macrophages and those with high MW chitosan in HCT-116.
Original languageEnglish
Pages (from-to)2594–2608
JournalBeilstein Journal of Nanotechnology
Volume2019
Issue number10
DOIs
Publication statusPublished - 30 Dec 2019

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