Brain Targeted Curcumin Loaded Turmeric Oil Microemulsion Protects Against Trimethyltin Induced Neurodegeneration in Adult Zebrafish: A Pharmacokinetic and Pharmacodynamic Insight.

PURPOSE: Aromatic turmerone, a major constituent of turmeric oil, has been recently reported for proliferation of neural stem cell showing great potential for effective treatment in neurodegenerative disorders. However, its effect as oral brain targeted formulation for neuroprotection has not yet reported. The objective of the study was to investigate the pharmacokinetic of curcumin loaded turmeric oil microemulsion for brain targeting and probing the protective effect against trimethyltin induced neurodegeneration in adult zebrafish. METHODS: Initially, in vivo plasma and brain pharmacokinetics was performed to determine improvement in relative bioavailability in rats followed by biodistribution and histopathological evaluation. Furthermore, the neuroprotective effect of the formulation was assessed in trimethyltin induced neurodegeneration model using adult zebrafish by behavioral analysis and biochemical analysis. RESULTS: The in vivo plasma and brain pharmacokinetics showed 2-fold and 1.87-fold improvement respectively. Biodistribution study revealed significantly lower concentration in organs other than brain. Furthermore, curcumin microemulsion exhibited improved spatial memory by remembering the training and made correct choices after curcumin microemulsion treatment than other treatment groups. Histopathological evaluation confirmed neuroprotective effect on zebrafish brains. The biochemical analysis revealed reduced oxidative stress in curcumin microemulsion treated group. CONCLUSIONS: Overall results showed a great potential of curcumin microemulsion for brain targeting in the effective treatment of neurological ailments.

Preparation, optimization and preliminary pharmacokinetic study of curcumin encapsulated turmeric oil microemulsion in zebra fish.

The present investigation aimed to develop curcumin loaded turmeric oil microemulsion for brain targeting. An effort has been made to investigate the role of functional components in developing brain targeted formulation which could enhance the bioavailability and uptake of drug in the brain upon oral administration. Preliminary studies like solubility study, emulsification study and construction of the pseudo ternary phase diagram were performed for screening components. The formulation was optimized by using extreme vertices mixture design. The optimized formulation was characterized for appearance, stability to centrifugation, dilution potential, globule size, zeta potential and drug content. Furthermore, ex-vivo permeation in chicken gut sac non everted technique and pharmacokinetic study in adult zebra fishes were carried out. The optimized formulation was found to clear, yellow-colored with the absence of phase separation and precipitation denoted the stability of formulation to centrifugation and dilution. The mean globule size, polydispersity index, zeta potential and drug content was observed as 29.13± 0.12 nm, 0.23 ± 0.01,-12.33 ± 1.37 mV and 99.10±3.91 %, respectively. Ex vivo permeation study revealed 2.41 fold enhancement in the steady-state flux when compared to curcumin solution. Furthermore, optimized formulation showed shorter Tmax (5 min) and higher AUC(0-∞) (7.93 µg/brain*min) compared to the curcumin solution which showed similar Tmax and AUC(0-∞) of 2.78 µg/brain*min after oral administration to zebra fishes revealing 3.97 fold enhancement. The results revealed enhanced ex vivo oral absorption and enhanced in vivo brain pharmacokinetics of curcumin via functional microemulsion in the zebra fish model.