AAPS PharmSciTech

, Volume 19, Issue 8, pp 3698–3711 | Cite as

Oral Brain-Targeted Microemulsion for Enhanced Piperine Delivery in Alzheimer’s Disease Therapy: In Vitro Appraisal, In Vivo Activity, and Nanotoxicity

  • Samar M. EtmanEmail author
  • Yosra S. R. Elnaggar
  • Doaa A. Abdelmonsif
  • Ossama Y. Abdallah
Research Article


Alzheimer’s disease (AD) is a neurodegenerative disorder that has no cure till now. Piperine (PIP) is an alkaloid characterized by memory-enhancing properties but challenging oral delivery obstacles. The objectives of this study are as follows: preparation of microemulsion (ME) as a proposed oral PIP nanocarrier for treatment of Alzheimer’s disease and testing its safety on the brain and other internal organs. This study employs bioactive surfactants in the common safe doses to improve PIP targeting to the brain. Selected ME systems encompassed Caproyl 90 (oil)/Tween 80/Cremophor RH 40 (surfactant) and Transcutol HP (co-surfactant). The particle size of the prepared formulations was less than 150 nm with negative zeta potential. The in vivo results showed a superior effect of ME over free PIP. Colchicine-induced brain toxicity results showed the safety of ME on brain cells. Nevertheless, toxicological results showed a potential ME nephrotoxicity. Oral microemulsion increased PIP efficacy and enhanced its delivery to the brain resulting in better therapeutic outcome compared to the free drug. However, the toxicity of this nanosystem should be carefully taken into consideration on chronic use.


piperine Alzheimer’s disease microemulsion nanotoxicology brain targeting 



Alzheimer’s disease






Bioactive excipient


Hydrophilic lipophilic balance


Transmission electron microscope




Sporadic dementia of Alzheimer’s type


Tumor necrosis factor-α


Zeta potential


Polydispersity index


Total antioxidant capacity




Superoxide dismutase activity


Acetylcholine esterase


Lethal dose


Blood-brain barrier


Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Supplementary material

12249_2018_1180_MOESM1_ESM.jpg (46 kb)
Supplementary figure 1 (JPG 46 kb)
12249_2018_1180_MOESM2_ESM.docx (15 kb)
Supplementary Table 1 (DOCX 14 kb)


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Copyright information

© American Association of Pharmaceutical Scientists 2018

Authors and Affiliations

  • Samar M. Etman
    • 1
    Email author
  • Yosra S. R. Elnaggar
    • 1
    • 2
  • Doaa A. Abdelmonsif
    • 3
  • Ossama Y. Abdallah
    • 1
  1. 1.Department of Pharmaceutics, Faculty of PharmacyAlexandria UniversityAlexandriaEgypt
  2. 2.Department of Pharmaceutics, Faculty of Pharmacy and Drug ManufacturingPharos University of AlexandriaAlexandriaEgypt
  3. 3.Department of Medical Biochemistry, Faculty of MedicineAlexandria UniversityAlexandriaEgypt

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