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• W2907176313 abstract "The blood-brain barrier (BBB) limits the therapeutic use of large molecules as it prevents them from passively entering the brain following administration by conventional routes. It also limits the capacity of researchers to study the role of large molecules in behavior, as it often necessitates intracerebroventricular administration. Oxytocin is a large-molecule neuropeptide with pro-social behavioral effects and therapeutic promise for social-deficit disorders. Although preclinical and clinical studies are using intranasal delivery of oxytocin to improve brain bioavailability, it remains of interest to further improve the brain penetrance and duration of action of oxytocin, even with intranasal administration. In this study, we evaluated a nanoparticle drug-delivery system for oxytocin, designed to increase its brain bioavailability through active transport and increase its duration of action through encapsulation and sustained release. We first evaluated transport of oxytocin-like large molecules in a cell-culture model of the BBB. We then determined in vivo brain transport using bioimaging and cerebrospinal fluid analysis in mice. Finally, we determined the pro-social effects of oxytocin (50 μg, intranasal) in two different brain targeting and sustained-release formulations. We found that nanoparticle formulation increased BBB transport both in vitro and in vivo. Moreover, nanoparticle-encapsulated oxytocin administered intranasally exhibited greater pro-social effects both acutely and 3 days after administration, in comparison to oxytocin alone, in mouse social-interaction experiments. These multimodal data validate this brain targeting and sustained-release formulation of oxytocin, which can now be used in animal models of social-deficit disorders as well as to enhance the brain delivery of other neuropeptides." @default.
• W2907176313 created "2019-01-11" @default.
• W2907176313 creator A5074179435 @default.
• W2907176313 creator A5085996942 @default.
• W2907176313 creator A5087345721 @default.
• W2907176313 creator A5089997249 @default.
• W2907176313 date "2019-02-01" @default.
• W2907176313 modified "2023-09-26" @default.
• W2907176313 title "Nanoparticle encapsulation increases the brain penetrance and duration of action of intranasal oxytocin" @default.
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• W2907176313 doi "https://doi.org/10.1016/j.yhbeh.2018.12.011" @default.
• W2907176313 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7001472" @default.
• W2907176313 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30593782" @default.
• W2907176313 hasPublicationYear "2019" @default.
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