Microfluidic mixing as platform technology for production of chitosan nanoparticles loaded with different macromolecules
In recent decades, biotechnological drugs have emerged as relevant therapeutic tools. However, therapeutic molecules can exert their activity only if properly formulated and delivered into the body. In this regard, nano-sized drug delivery systems have been shown to provide protection, stability, and controlled release of payloads, increasing their therapeutic efficacy. In this work, a microfluidic mixing technique for the preparation of chitosan-based nanoparticles was established with the capability of easily exchanging macromolecular biological cargos such as the model protein β-Galactosidase, mRNA, and siRNA. The nanoparticles obtained showed hydrodynamic diameters ranging from 75 nm to 105 nm, low polydispersity of 0.15 to 0.22 and positive zeta potentials of 6 mV to 17 mV.
All payloads were efficiently encapsulated (>80 %) and the well-known cytocompatibility of chitosan-based nanoparticles was confirmed. Cell culture studies demonstrated increased cellular internalization of loaded nano-formulations compared to free molecules as well as successful gene silencing with nano-formulated siRNA, suggesting the ability of these nanoparticles to escape the endosome.
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Materials
CS (5–20 mPa·s, 0.5 % in 0.5 % Acetic Acid at 20 °C, 1526.464 g/mol, 85 % deacetylation degree, CAS 9012–76-4) was purchased from Tokyo Chemical Industries (4–10-1 Nihonbashi-honcho, Chuo-ku, Tokyo 103–0023). TPP, β-galactosidase (bGal) from Aspergillus oryzae, ortho-nitrophenyl-β-galactoside (ONPG), sodium acetate, sodium bicarbonate, sodium phosphate monobasic, sodium phosphate dibasic, magnesium sulfate, D-(+)-glucose, β-mercaptoethanol, acetic acid 100 %, dimethyl sulfoxide (DMSO).
Antonietta Greco, Bettina Gabold, Siyu Chen, Xiaoxuan Wang, Zehua Xu, Achim Hartschuh, Enrica Chiesa, Ida Genta, Christian L. Ried, Thomas Merdan, Olivia M. Merkel, Microfluidic mixing as platform technology for production of chitosan nanoparticles loaded with different macromolecules, European Journal of Pharmaceutics and Biopharmaceutics, Volume 188, 2023, Pages 170-181, ISSN 0939-6411, https://doi.org/10.1016/j.ejpb.2023.05.010.
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