PUBLICATION

Piperine-loaded nanoparticles with enhanced dissolution and oral bioavailability for epilepsy control

Authors
Ren, T., Hu, M., Cheng, Y., Shek, T.L., Xiao, M., Ho, N.J., Zhang, C., Leung, S.S.Y., Zuo, Z.
ID
ZDB-PUB-190712-8
Date
2019
Source
European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences   137: 104988 (Journal)
Registered Authors
Keywords
Anti-epilepsy, Bioavailability, Dissolution, Nanoparticles, Piperine
MeSH Terms
  • Administration, Oral
  • Alkaloids/administration & dosage*
  • Alkaloids/chemistry
  • Alkaloids/pharmacokinetics
  • Animals
  • Anticonvulsants/administration & dosage*
  • Anticonvulsants/chemistry
  • Anticonvulsants/pharmacokinetics
  • Benzodioxoles/administration & dosage*
  • Benzodioxoles/chemistry
  • Benzodioxoles/pharmacokinetics
  • Biological Availability
  • Drug Liberation
  • Embryo, Nonmammalian
  • Epilepsy/drug therapy*
  • Male
  • Mice
  • Nanoparticles/administration & dosage*
  • Nanoparticles/chemistry
  • Piperidines/administration & dosage*
  • Piperidines/chemistry
  • Piperidines/pharmacokinetics
  • Polyunsaturated Alkamides/administration & dosage*
  • Polyunsaturated Alkamides/chemistry
  • Polyunsaturated Alkamides/pharmacokinetics
  • Rats, Sprague-Dawley
  • Tissue Distribution
  • Zebrafish
PubMed
31291598 Full text @ Eur. J. Pharm. Sci.
Abstract
Piperine, an alkaloid from black pepper, has demonstrated beneficial effects in central nervous system, especially in epilepsy control. However, its therapeutic application remains limited due to the low aqueous solubility of piperine. Thus, the present study aimed to formulate piperine into a more solubilized form to enhance its oral bioavailability and facilitate its development as a potential anti-epileptic treatment. The nanoprecipitation method was applied to prepare piperine nanoparticles, which were then examined under transmission electron microscopy. A spherical nanosized particle was obtained with small particle size (average particle size 130.20 ± 1.57 nm), narrow size distribution (polydispersity index 0.195 ± 0.002) and efficient entrapment (entrapment efficiency 92.2 ± 2.5%). Compared with the unformulated piperine, nanosized piperine had a much faster dissolution rate with 3 times higher accumulated drug release after 24 h. After oral administration at 3.5 mg/kg in rats, the nanosized piperine formulations could improve its oral bioavailability by 2.7-fold with 16 times higher concentrations in brain at 10 h postdosing. Moreover, the piperine nanoparticles exhibited effective protection against pentylenetetrazol-induced seizures in both zebrafish and mice. In summary, the present study provided a simple formulation strategy for oral administration of piperine to overcome its limitation in water solubility. The developed formulations could effectively enhance oral bioavailability of piperine with promising anti-epileptic effect, which could be applied as a potential therapy in epilepsy control.
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