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Polyethyleneimine-coated Iron Oxide Nanoparticles as a Vehicle for the Delivery of Small Interfering RNA to Macrophages In Vitro and In Vivo

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Modified Stability of microRNA-Loaded Nanoparticles.

Katja Fresacher-Scheiber¹, Ivana Ruseska¹, Henrik Siboni^1,2

¹Institute of Pharmaceutical Sciences, Department of Pharmaceutical Technology and Biopharmacy, University of Graz, Universitätsplatz 1, 8010 Graz, Austria.

|September 23, 2022

Summary

Functionalizing microRNA-protamine nanoparticles with citric acid enhances drug loading and cellular uptake while reducing binding affinity. This modification improves nanoparticle stability and enables controlled microRNA release for potential therapeutic applications.

Keywords:

binding affinity citric acid functionalization microRNA nanoparticles protamine

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Area of Science:

Biotechnology
Nanomedicine
Drug Delivery

Background:

MicroRNAs (miRNAs) show therapeutic potential for diseases like diabetes mellitus.
Efficient delivery of miRNAs remains a significant challenge in their clinical application.
Self-assembled miRNA-protein nanoparticles offer a promising strategy to overcome delivery obstacles.

Purpose of the Study:

To functionalize binary miRNA-protamine nanoparticles (proticles) with citric acid.
To reduce the binding strength between miRNA and protamine for improved dissociation.
To investigate the impact of citric acid on proticle colloidal stability, size, and drug loading.

Main Methods:

Formation of proticles by combining miRNA with protamine.
Functionalization of proticles with citric acid.
Analysis of colloidal stability, particle size distribution, and drug loading.
Atomic Force Microscopy (AFM) for structural investigation.
In vitro assessment of cellular toxicity and uptake pathways.

Main Results:

Citric acid functionalization influenced colloidal stability and maintained constant particle size and monodisperse distribution.
Citric acid addition increased miRNA drug loading capacity.
AFM revealed loosely complexed nanoparticles, with citric acid altering their shape.
Reduced binding affinity and nanoparticulate stability were observed.
Low cellular toxicity and consistent cellular uptake were demonstrated.

Conclusions:

Citric acid functionalization is a viable strategy to modulate miRNA-protamine nanoparticle properties.
The modification facilitates controlled miRNA release by reducing binding affinity.
The developed nanoparticles exhibit favorable characteristics for potential therapeutic delivery, including low toxicity and effective cellular uptake via active and passive routes.