Protective effect of surface-modified berberine nanoparticles against LPS-induced neurodegenerative changes: a preclinical study
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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.
KeywordsBerberine Chitosan Tween 80 Polyethylene glycol (PEG) Miltefosine Lipopolysaccharide Nanoparticles Neuroprotection
- Aβ 1-42
Amyloid beta 1-42
Total nitric oxide
Polyethylene glycol 4000
Thiobarbituric acid-reactive substances
Transmission electron microscopy
Tumor necrosis factor-alpha
Availability of data and materials
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.
Compliance with ethical standards
The authors declare that they have no competing interests.
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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