PUBLICATION
Solid-lipid nanoparticle formulation improves antiseizure action of cryptolepine
- Authors
- Mante, P.K., Adomako, N.O., Antwi, P., Kusi-Boadum, N.K., Osafo, N.
- ID
- ZDB-PUB-210210-14
- Date
- 2021
- Source
- Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 137: 111354 (Journal)
- Registered Authors
- Keywords
- Cav1.2 receptor, Cryptolepis, Epilepsy, Nanoparticles, Sigma 2 receptor, Zebrafish
- MeSH Terms
-
- Animals
- Anticonvulsants/administration & dosage
- Anticonvulsants/chemistry*
- Anticonvulsants/pharmacology*
- Blood-Brain Barrier
- Convulsants
- Cryptolepis/chemistry
- Drug Compounding
- Indole Alkaloids/administration & dosage
- Indole Alkaloids/chemistry*
- Indole Alkaloids/pharmacology*
- Male
- Motor Activity/drug effects
- Nanoparticles*
- Pentylenetetrazole
- Quinolines/administration & dosage
- Quinolines/chemistry*
- Quinolines/pharmacology*
- Receptors, Drug/metabolism
- Seizures/chemically induced
- Seizures/prevention & control
- Swimming
- Zebrafish
- PubMed
- 33561642 Full text @ Biomed. Pharmacother.
Citation
Mante, P.K., Adomako, N.O., Antwi, P., Kusi-Boadum, N.K., Osafo, N. (2021) Solid-lipid nanoparticle formulation improves antiseizure action of cryptolepine. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 137:111354.
Abstract
Following the high treatment gap and massive impact of epilepsy on global health particularly in low- and middle-income countries, our study aims to investigate cryptolepine, the major alkaloid of Cryptolepis sanguinolenta as well as its solid-lipid nanoparticle formulation for potential antiseizure activity. Cryptolepine was isolated and a solid-lipid formulation was prepared. Antiseizure activity of Solid-Lipid Nanoparticle formulation of cryptolepine (SLN-CRYP) was investigated using Pentylenetetrazole (PTZ)-induced model of seizure-like behaviors in Zebrafish with 2.5 and 5 mg/kg each of cryptolepine and SLN-CRYP. Drug receptor binding and permeability of the compound across the Blood Brain Barrier (BBB) were also assessed. SLN formulation of cryptolepine increased its permeability to the BBB from 0.32 × 10-6 cm/s to 10.81 × 10-6 cm/s. 2.5 and 5 mg/kg of SLN-CRYP significantly reduced mean seizure score (P = 0.0018; F(6, 63) = 23.52) and significantly increased (P < 0.0001; F(6, 63) = 65.41) latency to onset of seizures. The total distance swam by fish administered with 2.5 and 5 mg/kg of SLN-CRYP was significantly (P < 0.000; F(6, 63) = 161.9) decreased. 5 mg/kg of cryptolepine also significantly decreased swimming distance. Cryptolepine exhibited inhibitory modulation of human voltage-gated calcium channels (Cav1.2), H1-receptor, Peripheral Benzodiazepine Receptor and Sigma 2 receptor with a high Ki values of 6133.38 nM and 2945.0 nM, indicating less potent antagonism on Cav1.2 and Sigma 2 receptors compared to Nifedipine and Haloperidol respectively. This study reveals that the solid-lipid nanoparticle formulation of cryptolepine improves its BBB permeability and hence antiseizure activity.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping