CONTROLLED RELEASE BIOPOLYMER SYSTEMS FOR TUBERCULOSIS

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In spite of the availability of several powerful drugs, which could achieve a complete cure, opportunistic infections such as tuberculosis are a serious global problem. The main hurdle in achieving success of chemotherapy is non-compliance in taking the drugs. In order to solve this problem, we have investigated if we could deliver the antimycobacterial chemotherapy in one or few doses. We found that a single dose of isoniazid, given in an implant of a polylactic-co- glycolic acid (PLGA) co-polymer, was able to release sustained and therapeutically active levels for prolonged periods of 6-8 weeks using in vitro testing, as well as an established in vivo man-mouse model. In the current studies, we wish to investigate a totally non-solvent technique for formulation of the isoniazid/PLGA controlled release system, with the goal of developing a single-dose treatment for the 6- month short-course chemotherapy regimes for tuberculosis. A non-solvent formulation will greatly facilitate sample preparation under good manufacturing practices (GMP's), and also find more ready acceptance by the FDA when planning clinical trials. Alternatively, we plan to use preparations which can give effective levels of drug for up to 2 or 3 months and thus deliver the whole six month regimen with 2 or 3 bimonthly doses. Various technological aspects of formulation and characterizing such polymer preparations are included in the current study.