The Importance of Apparent PKa in the Development of Nanoparticles Encapsulating SiRNA and MRNA

Overview

Journal Trends Pharmacol Sci

Specialty Pharmacology

Date 2021 Apr 20

PMID 33875229

Citations 43

Authors

Pratikkumar Patel

Nurudeen Mohammed Ibrahim

Kun Cheng

Affiliations

Soon will be listed here.

Abstract

Polymer and lipid nanoparticles have been extensively used as carriers to address the biological barriers encountered in siRNA and mRNA delivery. We summarize the crucial role of nanoparticle charge and ionizability in complexing RNAs, binding to biological components, escaping from the endosome, and releasing RNAs into the cytoplasm. We highlight the significant impact of the apparent pKa of nanoparticles on their efficacy and toxicity, and the importance of optimizing pKa in the development of lead formulations for RNAs. We also discuss the feasibility of fine-tuning the pKa in nanoparticles and the applications of this approach in the optimization of delivery systems for RNAs.

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