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• W1541915068 abstract "An anionic chemical delivery system (aCDS) was designed and evaluated for brain-targeted delivery of testosterone (T). In this system, targeting is achieved through the use of a specific, (acyloxy)alkyl-phosphonate-type, targetor moiety. The systemically administered T-aCDS can enter the brain by passive transport due to its increased lipophilicity. Hydrolytic cleavage by esterases releases, via a chemically unstable, short-lived intermediate, a negatively charged, hydrophilic phosphonate compound (TP−). This is locked in the brain and should provide sustained, site-specific release of the active drug following a phosphorolytic attack by alkaline phosphatase or by phosphodiesterase. In vivo evaluations found maximum T-aCDS brain levels 5–10 min after administration; they fell under the detection-limit (<0.1 μg/g) after 60 min. With the employed (pivaloyloxy)methyl phosphonate ester, cleavage by esterases, the first metabolic step in the decomposition process, was not very fast. Maximum concentration of the decomposition product (TP−) was obtained at 30 min after administration; it did not decrease significantly during the study proving that this negatively charged intermediate is ‘locked in’ the brain. However, the phosphonate derivative of the secondary, hindered hydroxyl group in this product was fairly resistant to phosphorolytic attack, the second metabolic step. The released drug could not be detected indicating that testosterone release, if any, is slower than metabolism and/or elimination." @default.
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• W1541915068 date "1998-05-01" @default.
• W1541915068 modified "2023-10-17" @default.
• W1541915068 title "Targeted drug delivery to the brain via phosphonate derivatives" @default.
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• W1541915068 doi "https://doi.org/10.1016/s0378-5173(98)00025-8" @default.
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