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Protective effect of surface-modified berberine nanoparticles against LPS-induced neurodegenerative changes: a preclinical study

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Abstract

Berberine (BBR) exerts documented protection against neurodegenerative disorders. However, data on the effect of nano-encapsulation on the neuroprotective effect of BBR are lacking. We investigated the effect of BBR loading into chitosan (CS) nanoparticles (NPs) and their surface modification with Tween 80 (T80), polyethylene glycol 4000 (PEG), and miltefosine (MFS) against lipopolysaccharide (LPS)-induced neurodegenerative changes in addition to hepatotoxicity in rats. BBR-NPs were prepared by ionic gelation and characterized for morphology by transmission electron microscopy (TEM), colloidal properties, and entrapment efficiency (EE%). The neuroprotective and hepatoprotective effects of a 14-day pretreatment with four BBR-NPs formulations (4 mg/kg BBR/day) by intraperitoneal (i.p.) injection were challenged by a single i.p. 4 mg/kg dose of LPS on the fifteenth day. Neuroprotective efficacy and potential toxicity of BBR-NPs relative to BBR solution were assessed biochemically and histopathologically. One-way ANOVA followed by Tukey’s comparison test was used for statistical analysis. CS nano-encapsulation and surface modification of BBR-NPs altered the neuroprotective and hepatoprotective effects of BBR depending on the physicochemical and/or biological effects of BBR, CS, coating materials, and NP-related features. Similar to the prophylactic and treatment efficacy of NPs for brain delivery, safety of these nanostructures and their individual formulation components warrants due research attention.

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Abbreviations

AChE:

Acetylcholine esterase

Aβ 1-42:

Amyloid beta 1-42

ALT:

Alanine aminotransferase

AST:

Aspartate aminotransferase

CS:

Chitosan

GSH:

Reduced glutathione

LPS:

Lipopolysaccharide

MFS:

Miltefosine

NO:

Total nitric oxide

NPs:

Nanoparticles

PEG:

Polyethylene glycol 4000

TBARS:

Thiobarbituric acid-reactive substances

TEM:

Transmission electron microscopy

TNF-α:

Tumor necrosis factor-alpha

T80:

Tween 80

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Authors and Affiliations

  1. Department of Biotechnology, Institute of Graduate Studies and Research, Alexandria University, Alexandria, Egypt

    Salma A. Soudi & Salah A. Sheweita

  2. Department of Pharmaceutical Sciences, School of Pharmacy and Physician Assistant Studies (SOPPAS), University of Saint Joseph (USJ), Hartford, CT, 06103, USA

    Mohamed I. Nounou

  3. Department of Clinical Biochemistry, Faculty of Medicine, King Khalid University, Abha, Kingdom of Saudi Arabia

    Salah A. Sheweita

  4. Biological screening and preclinical trial laboratory, Department of Biochemistry, Faculty of Science, Alexandria University, Alexandria, Egypt

    Doaa A. Ghareeb

  5. Pharmaceutical and Fermentation Industries Development Center, City for Scientific Research and Technology Applications, Alexandria, Egypt

    Doaa A. Ghareeb

  6. Department of Pathology, Faculty of Medicine, Alexandria University, Alexandria, Egypt

    Layla K. Younis

  7. Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Alexandria, 21521, Egypt

    Labiba K. El-Khordagui

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  1. Salma A. Soudi
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  2. Mohamed I. Nounou
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  3. Salah A. Sheweita
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  4. Doaa A. Ghareeb
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  5. Layla K. Younis
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  6. Labiba K. El-Khordagui
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Contributions

SAS: data acquisition and contribution to data interpretation and manuscript drafting. MIN and LKE: Contribution to the study design, data analysis, and interpretation and major drafting and revision of the manuscript; SAS and DAG: contribution to the study design and biochemical assessments; LY: histopathological examination and data interpretation. SAS and LKE: responsibility for the integrity of the work. All authors read and approved the final manuscript.

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Correspondence to Mohamed I. Nounou.

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The authors declare that they have no competing interests.

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Animal handling and experimental protocols were approved by the Research Ethics Committee of the Medical Research Institute, Alexandria University (Alexandria, Egypt) and complied with the Guide for the Care and Use of Laboratory Animals issued by the National Research Council (US) Institute for Laboratory Animal Research (ILAR, 1996).

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Soudi, S.A., Nounou, M.I., Sheweita, S.A. et al. Protective effect of surface-modified berberine nanoparticles against LPS-induced neurodegenerative changes: a preclinical study. Drug Deliv. and Transl. Res. 9, 906–919 (2019). https://doi.org/10.1007/s13346-019-00626-1

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