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- W3199758623 abstract "Prolonged oxidative stress characterizes manywell-studied diseases of the central nervous system (CNS),including stroke. In 2015, stroke claimed the lives of over 140,000US citizens and from 2013-2014 cost $40.1 billion. An importantaspect of stroke pathology, brain oxidative stress, persists for upto 1 week following stroke, motivating the need for temporalcontrol of antioxidant drug delivery. N-acetylcysteine (NAC) is apotent small-molecule antioxidant. Poly(lactic-co-glycolic acid)(PLGA) microparticles have long been used to deliver encapsulateddrugs with temporal control, but encapsulation of small hydrophilicmolecules via traditional emulsion methods has been a challenge dueto rapid mass transport of small molecules out of particle pores.We have developed an alteration to the existingwater-in-oil-in-water (W/O/W) drug encapsulation method thatdramatically improves loading efficiency: doping external waterphases with drug to mitigate drug diffusion out of the particleduring fabrication. NAC-doped particles exhibited high loads andimproved outcomes of monolayer oligodendrocyte progenitor cells(OPCs) experiencing multiple doses of hydrogen peroxide byincreasing the intracellular glutathione content and preservingcellular viability relative to the injury control. NAC-dopedmicroparticles also protected OPC viability and morphology fromtoxicity of photoinitiators, molecules commonly used in contactwith cells to form hydrogels. To slow and lengthen the duration ofantioxidant release, the hydrophobic prodrug BDP-NAC wasencapsulated within the core of core/ shell microparticles. Thesecore/ shell microparticles protected OPC growth and viability fromseven daily doses of hydrogen peroxide. Drug delivery is alsouseful for proper neural development, encompassing both anterior(i.e., forebrain and midbrain) and posterior (i.e., hindbrain andspinal cord) tissue components, which appears to require opposingspatial gradients of a morphogen and its inhibitor. To meet thisneed, we designed microparticles that released active BMP-4, amorphogen, and its inhibitor Dkk-1, showing the potential use ofmicroparticles in spatially guiding neural tissue development.Thus, polymeric microparticles have the potential to providetemporally controlled drug therapy beneficial in neural disease andtissue development." @default.
- W3199758623 created "2021-09-27" @default.
- W3199758623 creator A5074529494 @default.
- W3199758623 date "2019-01-01" @default.
- W3199758623 modified "2023-09-23" @default.
- W3199758623 title "Investigation of Controlled Drug Release from PolymericMicroparticles on Models of Oxidative Disease and TissueDevelopment" @default.
- W3199758623 doi "https://doi.org/10.18130/v3-hhwj-qm05" @default.
- W3199758623 hasPublicationYear "2019" @default.
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