Research Project
3488929
Cerebral toxoplasmosis is the most common opportunistic disease affecting the brain of patients with acquired immune deficiency syndrome (AIDS). Sulfonamide treatment is initially effective in treating the infection but the regimen often causes side effects which limit therapy subsequently provoking relapse. This proposal suggests the development of brain-targeted delivery forms of the active antitoxoplasma agents such as sulfadiazine. This method selected to achieve selectivity is a dihydropyridine pyridinium salt redox type chemical delivery system (CDS). Various types of CDS's will be applied to the selected sulfa drugs. Analytical methodologies (HPLC) will be developed for the synthesized compounds. In vitro examinations including lipophilicity determination and compound stability both in chemical oxidants and in biological matrices will help to select a CDS for in vivo experimentation. A distribution study in rats will indicate whether the CDS satisfactorily performed its function as measured by brain retention of sulfonamide antibiotic relative to peripheral retention. Properly developed, a CDS for sulfonamide could improve therapy of toxoplasmosis by diverting a larger portion of the administered dose to the site of infection and reduce toxicities which are often dose-limiting.
