(230e) Development of Anti-Tubercular Nanoscale Drug Cocktails for Targeted Therapy

While tuberculosis (TB) is a curable intracellular disease, it remains a global health issue with over 1 million deaths reported in 2007. Causes of failed treatment include patient non-compliance and the emergence of drug resistance over the 6 month therapeutic course.  Advanced technologies are needed to improve the efficiency of drug delivery to reduce dosing frequency and limit drug resistance, while ensuring patient compliance.  Block copolymer directed rapid precipitations by Flash NanoPrecipitation enable formation of nanoparticles which have two unique advantages: (1) multiple drugs can be simultaneously assembled in the same nanoparticle and (2) targeting ligands can be introduced efficiently in drug formulations.  Using nanoparticles as a drug delivery platform, we have created nanoscale drug cocktails to colocalize a novel, potent anti-tubercular drug with an efflux pump blocker to ensure therapeutic doses are achieved intracellularly.  Targeted polyethylene glycol protected nanoparticles with variable mannose density on the surface have been studied in vitro to achieve optimized active targeting vehicles for anti-TB drug delivery specifically to macrophages.  To promote patient compliance, aerosol carrier particles have been developed for inhalable targeted delivery of nanoparticles to the lung, with predictable fine particle fractions.  The combination of these functionalities is a promising route to overcome some of the current treatment limitations in TB therapy.