Tuberculosis chemotherapy: current drug delivery approaches

Abstract

Tuberculosis is a leading killer of young adults worldwide and the global scourge of multi-drug resistant tuberculosis is reaching epidemic proportions. It is endemic in most developing countries and resurgent in developed and developing countries with high rates of human immunodeficiency virus infection. This article reviews the current situation in terms of drug delivery approaches for tuberculosis chemotherapy. A number of novel implant-, microparticulate-, and various other carrier-based drug delivery systems incorporating the principal anti-tuberculosis agents have been fabricated that either target the site of tuberculosis infection or reduce the dosing frequency with the aim of improving patient outcomes. These developments in drug delivery represent attractive options with significant merit, however, there is a requisite to manufacture an oral system, which directly addresses issues of unacceptable rifampicin bioavailability in fixed-dose combinations. This is fostered by the need to deliver medications to patients more efficiently and with fewer side effects, especially in developing countries. The fabrication of a polymeric once-daily oral multiparticulate fixed-dose combination of the principal anti-tuberculosis drugs, which attains segregated delivery of rifampicin and isoniazid for improved rifampicin bioavailability, could be a step in the right direction in addressing issues of treatment failure due to patient non-compliance.

Figure 1

Estimated TB incidence and mortality in 2003. Data extracted from WHO Tuberculosis data sheet [3].

Figure 2

Pathogenesis of TB.

Figure 3

Sites of action of the principal anti-TB drugs. Adapted in part from Rattan et al.; Parsons et al.; Somoskovi et al. [16,17,18].

Figure 4

Proposed mechanisms for interaction between RIF and INH: (a) Schiff's Reaction of RIF and INH, (b) Carbonyl Condensation of RIF and INH, (c) Fischer's Esterification Reaction between RIF and INH.