Drug Delivery and Translational Research

, Volume 9, Issue 5, pp 906–919 | Cite as

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

  • Salma A. Soudi
  • Mohamed I. NounouEmail author
  • Salah A. Sheweita
  • Doaa A. Ghareeb
  • Layla K. Younis
  • Labiba K. El-Khordagui
Original Article


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.


Berberine Chitosan Tween 80 Polyethylene glycol (PEG) Miltefosine Lipopolysaccharide Nanoparticles Neuroprotection 



Acetylcholine esterase

Aβ 1-42

Amyloid beta 1-42


Alanine aminotransferase


Aspartate aminotransferase




Reduced glutathione






Total nitric oxide




Polyethylene glycol 4000


Thiobarbituric acid-reactive substances


Transmission electron microscopy


Tumor necrosis factor-alpha


Tween 80


Availability of data and materials

Not applicable.

Authors’ 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.

Compliance with ethical standards

Competing interests

The authors declare that they have no competing interests.

Ethics approval

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).

Consent for publication

Not applicable.


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Copyright information

© Controlled Release Society 2019

Authors and Affiliations

  1. 1.Department of Biotechnology, Institute of Graduate Studies and ResearchAlexandria UniversityAlexandriaEgypt
  2. 2.Department of Pharmaceutical Sciences, School of Pharmacy and Physician Assistant Studies (SOPPAS)University of Saint Joseph (USJ)HartfordUSA
  3. 3.Department of Clinical Biochemistry, Faculty of MedicineKing Khalid UniversityAbhaKingdom of Saudi Arabia
  4. 4.Biological screening and preclinical trial laboratory, Department of Biochemistry, Faculty of ScienceAlexandria UniversityAlexandriaEgypt
  5. 5.Pharmaceutical and Fermentation Industries Development CenterCity for Scientific Research and Technology ApplicationsAlexandriaEgypt
  6. 6.Department of Pathology, Faculty of MedicineAlexandria UniversityAlexandriaEgypt
  7. 7.Department of Pharmaceutics, Faculty of PharmacyAlexandria UniversityAlexandriaEgypt

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