Pulmonary drug delivery of clofazimine: A route of administration and pharmacokinetics guided repositioning strategy against drug resistant tuberculosis informed by use for other disease indications. (2025)

Current oral therapeutic regime of clofazimine (CFZ) in tuberculosis treatment is limited by poor pharmacokinetics, long t, and especially exposure-related systemic toxicity. This review critically evaluates pulmonary administration as a targeted delivery approach to reduce the dose and improve therapeutic efficacy. From the primarily anti-leprotic indication, CFZ has evolved for the treatment of multidrug-resistant tuberculosis (MDR-TB), nontuberculous mycobacterial (NTM) diseases, small-cell lung cancer, and as an adjunct in therapies targeting immune checkpoints such as programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) in cancer patients. Despite broad-spectrum activity, clinical effectiveness is constrained by its poor physicochemical and p