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Dihydropyridine ⇄ pyridinium salt-based brain-selective delivery systems were synthesized for the progestins, ethisterone, norethindrone, and norgestrel. After initial lipophilicity and in vitro studies indicated the feasibility of applying these compounds to brain-specific delivery, in vivo distribution studies were performed on one of the redox delivery systems. After systemic administration of the chemical delivery system based on norethindrone, sustained and selective delivery of the oxidized form of the drug-carrier complex was observed in the brain. In addition, a slow and sustained release of the parent steroid, norethindrone, occurred. This release produced substantially higher levels of norethindrone for more prolonged periods than the administration of norethindrone itself. |
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