Inhaled drug therapy for treatment of tuberculosis

The lungs have received attention as a portal for drug delivery in tuberculosis (TB) from researchers addressing diverse objectives. These include: (a) targeting alveolar macrophages that harbour TB bacilli; (b) maintaining high drug concentrations in lung tissue; (c) systemic delivery of potent or second-line anti-TB agents; and (d) delivering agents that may change the host-pathogen dialectic. Formulation design considerations for each of the above objectives differ in slight, but important ways. As distinct from vaccine delivery formulations, inhalations intended for drug delivery are presumed to require chronic and repeated administration of larger amounts of material. This review seeks to summarize the consensus on the ways and means available or under development, to deliver different anti-TB agents as aerosols for inhalation. These agents include drugs in current clinical use, singly or in combination, experimental chemical entities, siRNA against host molecules, and finally, drugs in clinical use for unrelated pharmacological action, as modifiers of the host-pathogen dialectic. The pharmacokinetics of drug bioavailability in the lung, the blood and other tissues following lung deposition of inhaled therapies are also addressed. Finally, considerations on efficacy studies of drugs administered through aerosol delivery are discussed.