Brief CommunicationIn Vivo Evidence for Brain-to-Blood Efflux Transport of Valproic Acid across the Blood–Brain Barrier
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Cited by (19)
Modulation of the transport of valproic acid through the blood-brain barrier in rats by the Gastrodia elata extracts
2021, Journal of EthnopharmacologyCitation Excerpt :Since a high proportion of the protein-binding rate in the brain (Eain et al., 1984) and the transporter ability in the BBB of brain-to-blood efflux exceeds the blood-to-brain influx (Kakee et al., 2002), the VPA distribution in the brain is less than that of other anticonvulsant drugs. In addition, BBB transporters pumping out may resist VPA distribution into the brain (Kakee et al., 2002). Cyclosporin A (CsA) is regarded as a broad-spectrum multidrug resistance regulator that downmodulates P-gp, OATP, MRP and BCRP activities (Qadir et al., 2005).
Correction of Niemann-Pick type C1 trafficking and activity with the histone deacetylase inhibitor valproic acid
2020, Journal of Biological ChemistryCitation Excerpt :These data suggest that the I1061T mutations might alter the folding of NPC1 allowing for access of these lysine residues to a as yet to be characterized luminal deacetylase, which is sensitive to VPA-mediated silencing of HDAC7, which contributes to the trafficking defect seen with this disease-associated variant, an effect that is inhibited by VPA and by silencing the expression of HDAC7. The HDACi VPA is widely used in the treatment of many neurological conditions including epilepsy and bipolar disorder due to its ability to cross the BBB and its minimal toxicity during chronic administration in mouse models and in humans (113, 114). VPA has also exhibited therapeutic potential in mouse models of Alzheimer's disease (AD) (115) and amyotrophic lateral sclerosis (ALS) (116), suggesting that it is capable of modulating the folding and/or aggregation of disease-associated variant proteins.
Progress and perspectives of brain-targeting lipid-based nanosystems via the nasal route in Alzheimer's disease
2020, European Journal of Pharmaceutics and BiopharmaceuticsCitation Excerpt :Finally, NLCs were found to be more permeable through nose-to-brain as compared to the drug solution [168]In addition to the advantages that SLNs present, NLCs have improved drug encapsulation efficiency and release properties but unfortunately, they still have the drawback of rapid mucociliary clearance [169]. The carrier-mediated efflux transport process is known to play a role in the drug transportation of nasally applied NLCs to the brain [170], Transcellular transportation through the olfactory neurons is another mechanism to deliver NLCs to the brain via the various endocytic pathways of neuronal cells in the olfactory membrane [117,171]. It is also suggested that the transport of NLCs could be done by slow intraaxonal transport or by a faster transfer through the perineural space surrounding the nerve cells [172].
Generation-6 hydroxyl PAMAM dendrimers improve CNS penetration from intravenous administration in a large animal brain injury model
2017, Journal of Controlled ReleaseIncreasing pro-survival factors within whole brain tissue of Sprague Dawley rats via intracerebral administration of modified valproic acid
2015, Journal of Pharmacological SciencesCitation Excerpt :Cornford et al (15) reported the rat brain-to-blood efflux of radiolabeled VPA from CSF to be faster than that of water and such a change was observable within 4 min. Furthermore, Kakee et al (17) intracerebrally injected Sprague Dawley (SD) rats with 25 mM VPA and found an 89.1% removal after 5 min, which was not significantly different from their 100% clearance control. This perhaps explains how patients taking peripheral VPA have been reported to show wide variations in concentration ranging from 39 μM to 185 μM in brain tissue and 18 μM–262 μM in cerebrospinal fluid (CSF; (20)).
Transport of valproate at intestinal epithelial (Caco-2) and brain endothelial (RBE4) cells: Mechanism and substrate specificity
2008, European Journal of Pharmaceutics and Biopharmaceutics