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Design and characterization of Lactotransferrin peptide-loaded dextran-docosahexaenoic acid nanoparticles: an immune modulator for hepatic damage

The primary objective of this research was to create injectable delivery formulations using Lactotransferrin (LTF) peptide-loaded dextran nanoparticles coated with docosahexaenoic acid. These nanoparticles, designated as LLDDNP, underwent a lyophilization process. The study encompassed a comprehensi...

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Autores principales: Madkhali, Osama A., Moni, Sivakumar S., Sultan, Muhammad H., Bakkari, Mohammed Ali, Almoshari, Yosif, Shaheen, Emad Sayed, Alshammari, Abdulrahman
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10439908/
https://www.ncbi.nlm.nih.gov/pubmed/37598258
http://dx.doi.org/10.1038/s41598-023-40674-9
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author Madkhali, Osama A.
Moni, Sivakumar S.
Sultan, Muhammad H.
Bakkari, Mohammed Ali
Almoshari, Yosif
Shaheen, Emad Sayed
Alshammari, Abdulrahman
author_facet Madkhali, Osama A.
Moni, Sivakumar S.
Sultan, Muhammad H.
Bakkari, Mohammed Ali
Almoshari, Yosif
Shaheen, Emad Sayed
Alshammari, Abdulrahman
author_sort Madkhali, Osama A.
collection PubMed
description The primary objective of this research was to create injectable delivery formulations using Lactotransferrin (LTF) peptide-loaded dextran nanoparticles coated with docosahexaenoic acid. These nanoparticles, designated as LLDDNP, underwent a lyophilization process. The study encompassed a comprehensive investigation, including physicochemical characterization, in vivo assessment of biomarkers, and an examination of immune response through cytokine modulation. The zeta potential of LLDDNP was − 24.5 ± 12 mV, while their average particle size was 334.9 z.d.nm. The particles exhibited a conductivity of 2.10 mS/cm, while their mobility in the injectable dosage form was measured at − 3.65 µm cm/Vs. The scanning electron microscopy investigation, the lyophilization processes resulted in discrete particles forming particle aggregations. However, transmission electron microscopy analysis revealed that LLDDNP is spherical and smooth. The thermogram showed that about 95% of LLDDNP's weight was lost at 270 °C, indicating that the particles are extremely thermal stable. The XRD analysis of LLDDNP exhibited clear and distinctive peaks at 2θ angles, specifically at 9.6°, 20.3°, 21.1°, 22°, 24.6°, 25.2°, 36°, and 44.08°, providing compelling evidence of the crystalline nature of the particles. According to proton NMR studies, the proton dimension fingerprint region of LLDDNP ranges from 1.00 to 1.03 ppm. The in vitro release of LTF from LLDDNP was found to follow zero-order kinetics, with a commendable R(2) value of 0.942, indicating a consistent and predictable release pattern over time. The in vivo investigation revealed a significant impact of hepatotoxicity on the elevation of various cytokines, including IL-1β, IL-6, IL-8R, TNF-α, IL-2, IL-4, IL-10, and IFN-γ. Additionally, the presence of hepatotoxicity led to an increase in apoptosis markers, namely caspase 3 and caspase 9, as well as elevated levels of liver biomarkers such as CRP, ALP, ALT, and AST. In contrast, the treatment with LLDDNP modulated the levels of all biomarkers, including cytokines level in the treatment group extremely high significant at p < 0.001.
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spelling pubmed-104399082023-08-21 Design and characterization of Lactotransferrin peptide-loaded dextran-docosahexaenoic acid nanoparticles: an immune modulator for hepatic damage Madkhali, Osama A. Moni, Sivakumar S. Sultan, Muhammad H. Bakkari, Mohammed Ali Almoshari, Yosif Shaheen, Emad Sayed Alshammari, Abdulrahman Sci Rep Article The primary objective of this research was to create injectable delivery formulations using Lactotransferrin (LTF) peptide-loaded dextran nanoparticles coated with docosahexaenoic acid. These nanoparticles, designated as LLDDNP, underwent a lyophilization process. The study encompassed a comprehensive investigation, including physicochemical characterization, in vivo assessment of biomarkers, and an examination of immune response through cytokine modulation. The zeta potential of LLDDNP was − 24.5 ± 12 mV, while their average particle size was 334.9 z.d.nm. The particles exhibited a conductivity of 2.10 mS/cm, while their mobility in the injectable dosage form was measured at − 3.65 µm cm/Vs. The scanning electron microscopy investigation, the lyophilization processes resulted in discrete particles forming particle aggregations. However, transmission electron microscopy analysis revealed that LLDDNP is spherical and smooth. The thermogram showed that about 95% of LLDDNP's weight was lost at 270 °C, indicating that the particles are extremely thermal stable. The XRD analysis of LLDDNP exhibited clear and distinctive peaks at 2θ angles, specifically at 9.6°, 20.3°, 21.1°, 22°, 24.6°, 25.2°, 36°, and 44.08°, providing compelling evidence of the crystalline nature of the particles. According to proton NMR studies, the proton dimension fingerprint region of LLDDNP ranges from 1.00 to 1.03 ppm. The in vitro release of LTF from LLDDNP was found to follow zero-order kinetics, with a commendable R(2) value of 0.942, indicating a consistent and predictable release pattern over time. The in vivo investigation revealed a significant impact of hepatotoxicity on the elevation of various cytokines, including IL-1β, IL-6, IL-8R, TNF-α, IL-2, IL-4, IL-10, and IFN-γ. Additionally, the presence of hepatotoxicity led to an increase in apoptosis markers, namely caspase 3 and caspase 9, as well as elevated levels of liver biomarkers such as CRP, ALP, ALT, and AST. In contrast, the treatment with LLDDNP modulated the levels of all biomarkers, including cytokines level in the treatment group extremely high significant at p < 0.001. Nature Publishing Group UK 2023-08-19 /pmc/articles/PMC10439908/ /pubmed/37598258 http://dx.doi.org/10.1038/s41598-023-40674-9 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Madkhali, Osama A.
Moni, Sivakumar S.
Sultan, Muhammad H.
Bakkari, Mohammed Ali
Almoshari, Yosif
Shaheen, Emad Sayed
Alshammari, Abdulrahman
Design and characterization of Lactotransferrin peptide-loaded dextran-docosahexaenoic acid nanoparticles: an immune modulator for hepatic damage
title Design and characterization of Lactotransferrin peptide-loaded dextran-docosahexaenoic acid nanoparticles: an immune modulator for hepatic damage
title_full Design and characterization of Lactotransferrin peptide-loaded dextran-docosahexaenoic acid nanoparticles: an immune modulator for hepatic damage
title_fullStr Design and characterization of Lactotransferrin peptide-loaded dextran-docosahexaenoic acid nanoparticles: an immune modulator for hepatic damage
title_full_unstemmed Design and characterization of Lactotransferrin peptide-loaded dextran-docosahexaenoic acid nanoparticles: an immune modulator for hepatic damage
title_short Design and characterization of Lactotransferrin peptide-loaded dextran-docosahexaenoic acid nanoparticles: an immune modulator for hepatic damage
title_sort design and characterization of lactotransferrin peptide-loaded dextran-docosahexaenoic acid nanoparticles: an immune modulator for hepatic damage
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10439908/
https://www.ncbi.nlm.nih.gov/pubmed/37598258
http://dx.doi.org/10.1038/s41598-023-40674-9
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