Pulmonary delivery of isoxyl particles to treat Mycobacterium tuberculosis Public Deposited

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Last Modified
  • March 21, 2019
Creator
  • Wang, Chenchen
    • Affiliation: Eshelman School of Pharmacy, Division of Pharmacoengineering and Molecular Pharmaceutics
Abstract
  • Isoxyl is an effective drug to treat multi-drug resistant tuberculosis but its use was impaired by failure in clinical trials. Due to absence of reliable quantitive analytical methods at that time, the reasons for these poor in-vivo outcomes were not determined. In the present work, an HPLC method was developed and validated for determination of isoxyl concentrations in plasma. Pilot studies showed that therapeutic plasma concentrations were not achieved after oral administration of isoxyl to guinea pigs. Pulmonary delivery may rescue the drug by targeting isoxyl particles to macrophages, the host cells of mycobacteria. Isoxyl particles with various size and shape were prepared by antisolvent precipitation. Subsequent spray drying produced microparticles < 5 μm suitable for lung delivery. Isoxyl > 5 μg/ml, independent of particle form, seemed effective in killing intracellular mycobacteria without cytotoxicity. This work is the basis for reviving drugs with undesired physicochemical properties to treat lung infection.
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  • In Copyright
Note
  • "... in partial fulfillment of the requirements for the degree of Master of Science in the Department of Molecular Pharmaceutics."
Advisor
  • Hickey, Anthony J.
Degree granting institution
  • University of North Carolina at Chapel Hill
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Place of publication
  • Chapel Hill, NC
Access
  • Open access
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