Characterisation, in‐vitro and in‐vivo evaluation of valproic acid‐loaded nanoemulsion for improved brain bioavailability

Objective This study was aimed to investigate the potential of formulated valproic acid‐encapsulated nanoemulsion (VANE) to improve the brain bioavailability of valproic acid (VPA). Methods Valproic acid‐encapsulated nanoemulsions were formulated and physically characterised (osmolarity, viscosity,...

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Bibliographic Details
Published in:Journal of pharmacy and pharmacology 2017-11, Vol.69 (11), p.1447-1457
Main Authors: Tan, Suk Fei, Kirby, Brian P., Stanslas, Johnson, Basri, Hamidon Bin
Format: Article
Language:English
Subjects:
Acids
Animals
Anticonvulsants - administration & dosage
Anticonvulsants - pharmacokinetics
Anticonvulsants - toxicity
Area Under Curve
Bioavailability
Biological Availability
Blood levels
Blood-brain barrier
Blood-Brain Barrier - metabolism
Brain - metabolism
Cell Line
Chemistry, Pharmaceutical
Cytotoxicity
Drug Compounding
Drug Delivery Systems
Drug Liberation
Emulsions
Encapsulation
Half-Life
Humans
in‐vitro model
Membrane permeability
Nanoemulsions
Nanoparticles
Osmolarity
parenteral nanoemulsion
Permeability
pharmacokinetics
Prolongation
Rats
Rats, Sprague-Dawley
Tissue Distribution
Valproic acid
Valproic Acid - administration & dosage
Valproic Acid - pharmacokinetics
Valproic Acid - toxicity
Vanes
Viscosity
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Summary:Objective This study was aimed to investigate the potential of formulated valproic acid‐encapsulated nanoemulsion (VANE) to improve the brain bioavailability of valproic acid (VPA). Methods Valproic acid‐encapsulated nanoemulsions were formulated and physically characterised (osmolarity, viscosity, drug content, drug encapsulation efficiency). Further investigations were also conducted to estimate the drug release, cytotoxic profile, in‐vitro blood–brain barrier (BBB) permeability, pharmacokinetic parameter and the concentration of VPA and VANE in blood and brain. Key findings Physical characterisation confirmed that VANE was suitable for parenteral administration. Formulating VPA into nanoemulsion significantly reduced the cytotoxicity of VPA. In‐vitro drug permeation suggested that VANEs crossed the BBB as freely as VPA. Pharmacokinetic parameters of VANE‐treated rats in plasma and brain showed F3 VANE had a remarkable improvement in AUC, prolongation of half‐life and reduction in clearance compared to VPA. Given the same extent of in‐vitro BBB permeation of VPA and VANE, the higher bioavailability of VANE in brain was believed to have due to higher concentration of VANE in blood. The brain bioavailability of VPA was improved by prolonging the half‐life of VPA by encapsulating it within the nanoemulsion‐T80. Conclusions Nanoemulsion containing VPA has alleviated the cytotoxic effect of VPA and improved the plasma and brain bioavailability for parenteral delivery of VPA.
ISSN:0022-3573
2042-7158
DOI:10.1111/jphp.12800