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Development and Characterization of Cationic Nanostructured Lipid Carriers as Drug Delivery Systems for miRNA-27a
Although miRNA-27a has been identified as a promising candidate for miRNA mimic therapy of obesity, its application is limited due to enzymatic degradation and low membrane permeation. To overcome these problems, we developed cationic nanostructured lipid carriers (cNLCs) using high-pressure homogen...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10384247/ https://www.ncbi.nlm.nih.gov/pubmed/37513917 http://dx.doi.org/10.3390/ph16071007 |
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author | Tucak-Smajić, Amina Ruseska, Ivana Letofsky-Papst, Ilse Vranić, Edina Zimmer, Andreas |
author_facet | Tucak-Smajić, Amina Ruseska, Ivana Letofsky-Papst, Ilse Vranić, Edina Zimmer, Andreas |
author_sort | Tucak-Smajić, Amina |
collection | PubMed |
description | Although miRNA-27a has been identified as a promising candidate for miRNA mimic therapy of obesity, its application is limited due to enzymatic degradation and low membrane permeation. To overcome these problems, we developed cationic nanostructured lipid carriers (cNLCs) using high-pressure homogenization and used them as non-viral carriers for the anti-adipogenic miRNA-27a. Cargo-free octadecylamine-containing NLCs and miRNA/cNLC complexes were characterized regarding particle size, size distributions, zeta potential, pH values, particle topography and morphology, and entrapment efficacy. Furthermore, the cytotoxicity and cellular uptake of the miRNA/cNLC complex in the 3T3-L1 cell line were investigated. The investigation of the biological effect of miRNA-27a on adipocyte development and an estimation of the accumulated Oil-Red-O (ORO) dye in lipid droplets in mature adipocytes were assessed with light microscopy and absorbance measurements. The obtained data show that cNLCs represent a suitable DDS for miRNAs, as miRNA/cNLC particles are rapidly formed through non-covalent complexation due to electrostatic interactions between both components. The miRNA-27a/cNLC complex induced an anti-adipogenic effect on miRNA-27a by reducing lipid droplet accumulation in mature adipocytes, indicating that this approach might be used as a new therapeutic strategy for miRNA mimic replacement therapies in the prevention or treatment of obesity and obesity-related disorders. |
format | Online Article Text |
id | pubmed-10384247 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-103842472023-07-30 Development and Characterization of Cationic Nanostructured Lipid Carriers as Drug Delivery Systems for miRNA-27a Tucak-Smajić, Amina Ruseska, Ivana Letofsky-Papst, Ilse Vranić, Edina Zimmer, Andreas Pharmaceuticals (Basel) Article Although miRNA-27a has been identified as a promising candidate for miRNA mimic therapy of obesity, its application is limited due to enzymatic degradation and low membrane permeation. To overcome these problems, we developed cationic nanostructured lipid carriers (cNLCs) using high-pressure homogenization and used them as non-viral carriers for the anti-adipogenic miRNA-27a. Cargo-free octadecylamine-containing NLCs and miRNA/cNLC complexes were characterized regarding particle size, size distributions, zeta potential, pH values, particle topography and morphology, and entrapment efficacy. Furthermore, the cytotoxicity and cellular uptake of the miRNA/cNLC complex in the 3T3-L1 cell line were investigated. The investigation of the biological effect of miRNA-27a on adipocyte development and an estimation of the accumulated Oil-Red-O (ORO) dye in lipid droplets in mature adipocytes were assessed with light microscopy and absorbance measurements. The obtained data show that cNLCs represent a suitable DDS for miRNAs, as miRNA/cNLC particles are rapidly formed through non-covalent complexation due to electrostatic interactions between both components. The miRNA-27a/cNLC complex induced an anti-adipogenic effect on miRNA-27a by reducing lipid droplet accumulation in mature adipocytes, indicating that this approach might be used as a new therapeutic strategy for miRNA mimic replacement therapies in the prevention or treatment of obesity and obesity-related disorders. MDPI 2023-07-14 /pmc/articles/PMC10384247/ /pubmed/37513917 http://dx.doi.org/10.3390/ph16071007 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Tucak-Smajić, Amina Ruseska, Ivana Letofsky-Papst, Ilse Vranić, Edina Zimmer, Andreas Development and Characterization of Cationic Nanostructured Lipid Carriers as Drug Delivery Systems for miRNA-27a |
title | Development and Characterization of Cationic Nanostructured Lipid Carriers as Drug Delivery Systems for miRNA-27a |
title_full | Development and Characterization of Cationic Nanostructured Lipid Carriers as Drug Delivery Systems for miRNA-27a |
title_fullStr | Development and Characterization of Cationic Nanostructured Lipid Carriers as Drug Delivery Systems for miRNA-27a |
title_full_unstemmed | Development and Characterization of Cationic Nanostructured Lipid Carriers as Drug Delivery Systems for miRNA-27a |
title_short | Development and Characterization of Cationic Nanostructured Lipid Carriers as Drug Delivery Systems for miRNA-27a |
title_sort | development and characterization of cationic nanostructured lipid carriers as drug delivery systems for mirna-27a |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10384247/ https://www.ncbi.nlm.nih.gov/pubmed/37513917 http://dx.doi.org/10.3390/ph16071007 |
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