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Cell medium-dependent dynamic modulation of size and structural transformations of binary phospholipid/ω-3 fatty acid liquid crystalline nano-self-assemblies: Implications in interpretation of cell uptake studies

Lookup NU author(s): Professor Moein MoghimiORCiD

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

© 2021 The Author(s)Lyotropic non-lamellar liquid crystalline (LLC) nanoparticles, with their tunable structural features and capability of loading a wide range of drugs and reporter probes, are emerging as versatile injectable nanopharmaceuticals. Secondary emulsifiers, such as Pluronic block copolymers, are commonly used for colloidal stabilization of LLC nanoparticles, but their inclusion often compromises the biological safety (e.g., poor hemocompatibility and enhanced cytotoxicity) of the formulation. Here, we introduce a library of colloidally stable, structurally tunable, and pH-responsive lamellar and non-lamellar liquid crystalline nanoparticles from binary mixtures of a phospholipid (phosphatidylglycerol) and three types of omega-3 fatty acids (ω-3 PUFAs), prepared in the absence of a secondary emulsifier and organic solvents. We study formulation size distribution, morphological heterogeneity, and the arrangement of their internal self-assembled architectures by nanoparticle tracking analysis, synchrotron small-angle X-ray scattering, and cryo-transmission electron microscopy. The results show the influence of type and concentration of ω-3 PUFAs in nanoparticle structural transitions spanning from a lamellar (Lα) phase to inverse discontinuous (micellar) cubic Fd3m and hexagonal phase (H2) phases, respectively. We further report on cell-culture medium-dependent dynamic fluctuations in nanoparticle size, number and morphology, and simultaneously monitor uptake kinetics in two human cell lines. We discuss the role of these multiparametric biophysical transformations on nanoparticle-cell interaction kinetics and internalization mechanisms. Collectively, our findings contribute to the understanding of fundamental steps that are imperative for improved engineering of LLC nanoparticles with necessary attributes for pharmaceutical development.


Publication metadata

Author(s): Bor G, Salentinig S, Sahin E, Nur Odevci B, Roursgaard M, Liccardo L, Hamerlik P, Moghimi SM, Yaghmur A

Publication type: Article

Publication status: Published

Journal: Journal of Colloid and Interface Science

Year: 2022

Volume: 606

Issue: 1

Pages: 464-479

Print publication date: 15/01/2022

Online publication date: 04/08/2021

Acceptance date: 29/07/2021

Date deposited: 23/08/2021

ISSN (print): 0021-9797

ISSN (electronic): 1095-7103

Publisher: Academic Press Inc.

URL: https://doi.org/10.1016/j.jcis.2021.07.149

DOI: 10.1016/j.jcis.2021.07.149


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Funding

Funder referenceFunder name
Danish Council for Independent Research | Technology and Production Sciences, reference DFF-7017-00065 (to AY & SMM)

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