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Inhaled Drug Delivery for Tuberculosis Therapy

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Abstract

One third of the world population is infected with tuberculosis (TB), and new infections occur at a rate of one per second. The recent increase in the emergence of drug-resistant strains of Mycobacterium tuberculosis and the dearth of anti-TB drugs is threatening the future containment of TB. New drugs or delivery systems that will stop the spread of TB and slow down or prevent the development of drug-resistant strains are urgently required. One of the reasons for the emergence of drug-resistant strains is the exposure of mycobacteria to sub-therapeutic levels of one or more antibiotics. Lung lesions containing large numbers of bacteria are poorly vascularized and are fortified with thick fibrous tissue; conventional therapy by the oral and parenteral routes may provide sub-therapeutic levels of anti-TB drugs to these highly sequestered organisms. Administering drugs by the pulmonary route to the lungs allows higher drug concentrations in the vicinity of these lesions. Supplementing conventional therapy with inhaled anti-TB therapy may allow therapeutic concentrations of drug to penetrate effectively into lung lesions and treat the resident mycobacteria.

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Abbreviations

AFB:

Acid-fast bacilli

AMΦ:

Alveolar Macrophage

APC:

Antigen presenting cells

BAL:

Bronco-alveolar lavage

CF:

Cystic fibrosis

CMI:

Cell mediated immunity

DTH:

Delayed-type hypersensitivity

EMB:

Ethambutol

INH:

Isoniazid

Inhl:

Inhalation

IV:

Intravenous

GI:

Gastro-intestinal

MDR:

Multi-drug resistant

Mtb:

Mycobacterium tuberculosis

PD:

Pharmacodynamic

PK:

Pharmacokinetic

PLGA:

Poly(lactic-co-glycolic acid)

PNAPs:

Porous nanoparticle aggregate particles

PZA:

Pyrazinamide

RIF:

Rifampicin

STR:

Streptomycin

TB:

Tuberculosis

XDR:

Extremely-drug resistant

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ACKNOWLEDGEMENTS

The authors gratefully acknowledge the financial support of the not-for-profit organization Medicine in Need. The achievements of this organization are cited in the manuscript. The authors are particularly grateful to Drs. David Edwards and Bernard Fourie for their leadership and encouragement in the effort to bring aerosol TB therapy to patients. In addition, Dr. Hickey is grateful for the financial support of Pfizer, Inc. It is largely at the suggestion of Drs. Ljiljana Harding and Christopher Grainger that this manuscript was prepared.

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  1. Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, Kerr Hall, Campus Box # 7571–Room #–1310, Chapel Hill, North Carolina, 27599, USA

    Pavan Muttil, Chenchen Wang & Anthony J. Hickey

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  1. Pavan Muttil
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  2. Chenchen Wang
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Correspondence to Anthony J. Hickey.

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Muttil, P., Wang, C. & Hickey, A.J. Inhaled Drug Delivery for Tuberculosis Therapy. Pharm Res 26, 2401–2416 (2009). https://doi.org/10.1007/s11095-009-9957-4

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