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.
METHODS: Plasma from children and adults with P. vivax malaria in Sabah, Malaysia, were collected during acute infection, 7 and 28 days after drug treatment. Complement-fixing antibodies and immunoglobulin M and G (IgM and IgG), targeting 3 distinctive regions of PvMSP3α, were measured by means of enzyme-linked immunosorbent assay.
RESULTS: The seroprevalence of complement-fixing antibodies was highest against the PvMSP3α central region (77.6%). IgG1, IgG3, and IgM were significantly correlated with C1q fixation, and both purified IgG and IgM were capable of mediating C1q fixation to PvMSP3α. Complement-fixing antibody levels were similar between age groups, but IgM was predominant in children and IgG3 more prevalent in adults. Levels of functional antibodies increased after acute infection through 7 days after treatment but rapidly waned by day 28.
CONCLUSION: Our study demonstrates that PvMSP3α antibodies acquired during P. vivax infection can mediate complement fixation and shows the important influence of age in shaping these specific antibody responses. Further studies are warranted to understand the role of these functional antibodies in protective immunity against P. vivax malaria.