Abstract:
Aiming to improve the treatment outcomes of current daily tuberculosis (TB) chemotherapy
over several months, we investigated whether nanoencapsulation of existing drugs would allow
decreasing the treatment frequency to weekly, thereby ultimately improving patient compliance.
Nanoencapsulation of three first-line anti-TB drugs was achieved by a unique, scalable spray-drying
technology forming free-flowing powders in the nanometer range with encapsulation efficiencies of
82, 75, and 62% respectively for rifampicin, pyrazinamide, and isoniazid. In a pre-clinical study on TB
infected mice, we demonstrate that the encapsulated drugs, administered once weekly for nine weeks,
showed comparable efficacy to daily treatment with free drugs over the same experimental period.
Both treatment approaches had equivalent outcomes for resolution of inflammation associated with
the infection of lungs and spleens. These results demonstrate how scalable technology could be used
to manufacture nanoencapsulated drugs. The formulations may be used to reduce the oral dose
frequency from daily to once weekly in order to treat uncomplicated TB.
