Lipid nanocapsules for the nose-to-brain delivery of the anti-inflammatory bioactive lipid PGD-G.
(2023) Nanomedicine : nanotechnology, biology, and medicine — Vol. 48, p. 102633 (2023)
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- Here, prostaglandin D-glycerol ester (PGD-G) was selected to target neuroinflammation. As PGD-G is reported to have a short plasmatic half-life, we propose to use lipid nanocapsules (LNC) as vehicle to safely transport PGD-G to the central nervous system (CNS). PGD-G-loaded LNC (PGD-G-LNC) reduced pro-inflammatory cytokine expression in activated microglial cells, even so after crossing a primary olfactory cell monolayer. A single nasal administration of PGD-G-LNC in lipopolysaccharide (LPS)-treated mice reduced pro-inflammatory cytokine expression in the olfactory bulb. Coating LNC's surface with a cell-penetrating peptide, transactivator of transcription (TAT), increased its accumulation in the brain. Although TAT-coated PGD-G-LNC modestly exerted its anti-inflammatory effect in a mouse model of multiple sclerosis similar to free PGD-G after nasal administration, TAT-coated LNC surprisingly reduced the expression of pro-inflammatory chemokines in the CNS. These data propose LNC as an interesting drug delivery tool and TAT-coated PGD-G-LNC remains a good candidate, in need of further work.
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Mwema, A., Bottemanne, P., Paquot, A., Ucakar, B., Vanvarenberg, K., Al Houayek, M., Muccioli, G., & des Rieux, A. (2023). Lipid nanocapsules for the nose-to-brain delivery of the anti-inflammatory bioactive lipid PGD-G. Nanomedicine : nanotechnology, biology, and medicine, 48, 102633. https://doi.org/10.1016/j.nano.2022.102633 (Original work published 2023)