Efficacy of Dual-Targeting Combined Anti-Tuberculosis Drug Delivery System in the Treatment of Tuberculous Meningitis

Abstract

Tuberculous meningitis (TBM) is an incurable disease with high mortality. It is an extrapulmonary tuberculosis caused by mycobacterium tuberculosis which penetrated the blood-brain barrier and infected the meninges. Mycobacterium tuberculosis lurking in the body mainly reside in macrophages. Anti-tuberculous drugs usually can not target the blood-brain barrier and macrophages, the drug concentration in the lesion is low, which cannot effectively kill mycobacterium tuberculosis, making TBM difficult to treat. Targeted drug delivery systems can target drugs to specific nidus. In the study, we constructed a drug delivery system, which was a cell penetrate peptide B6 and phosphatidylserine (PS) modified polyethylene glycol (PEG) nanomaterial to target the blood-brain barrier and to target macrophages. This nanomaterial was a combined anti-tuberculosis drug delivery system encapsulating antituberculosis drugs rifampicin and pyrazinamide, designed to target macrophages in the brain and kill mycobacterium tuberculosis lurking in the macrophages. We have physically characterized the drug delivery system, and verified the bactericidal ability at cellular and animal level. Results have shown that the targeted drug delivery system had a remarkable efficacy to treat TBM in mice.