Scope for scalable smart formulations for enhanced drug delivery in Tuberculosis Dr. Yolandy Lemmer Council for Scientific and Industrial Research, Pretoria, South Africa Background: The complexity of drug delivery to pathogenic bacilli that are located within granulomas poses a pronounced challenge for the development of novel treatment programmes to combat tuberculosis. In general, high drug dose levels need to be administered to compensate for the progressive decrease in drug concentrations from the plasma to the macrophage and then finally reaching the bacilli, with concomitant drug induced toxicities and poor patient compliance. Nanoencapsulation of existing drugs with or without targeting ligands have shown the potential to solve this problem, but is challenged by costs of large scale production incurred by sourcing of raw materials and the encapsulation technology itself. Methods: PLGA nanoencapsulation of existing TB drugs has been achieved, with various approaches to reduce cost and improve production by smart formulations and innovative manufacturing strategies. Results: We disclose a successful attempt at drug nanoencapsulation with technologies including unique formulation and spray drying, which is anticipated to make it fully scalable to the industrial level, allowing for an easier entry into large scale production for delivery to the market. Conclusion: Pre-clinical studies clearly demonstrated that our encapsulated formulations showed improved comparative efficacy of treatment when compared to the free drugs alone. These results indicate the sustained efficacy of encapsulated drugs and potential for reducing the dosing frequency to treat uncomplicated TB. The most prominent difference compared to existing state of the art is the easily scalable spray drying technology that we describe. The results emphasize the importance of innovation planning when considering new smart nanomedicine formulations for treatment: scalability of the process must always be considered for a feasible product outcome.