Review of inhalable nanoparticles for the pulmonary delivery of anti-tuberculosis drugs

Abstract

Tuberculosis is an airborne disease caused by the pathogen, Mycobacterium tuberculosis, which predominantly affects the lungs. World Health Organization (WHO) has reported that about 85% of TB patients are cured with the existing 6-month antibiotic regimen. However, the lengthy oral administration of high-dose anti-TB drugs is associated with significant side effects and leads to drug resistance cases. Alternatively, reformulating existing anti-tubercular drugs into inhalable nanoparticulate systems is a promising strategy to overcome the challenges associated with oral treatment as they could enhance drug retention in the pulmonary region to achieve an optimal drug concentration in the infected lungs. Hence, this review provides an overview of the literature on inhalable nano-formulations for the delivery of anti-TB drugs, including their formulation techniques and preclinical evaluations between the years 2000 and 2020, gathered from electronic journals via online search engines such as Google Scholar and PubMed. Previous in vitro and in vivo studies highlighted that the nano-size, low toxicity, and high efficacy were among the factors influencing the fate of nanoparticulate system upon deposition in the lungs. Although many preclinical studies have shown that inhalable nanoparticles increased therapeutic efficacy and minimised adverse drug reactions when delivered through the pulmonary route, none of them has progressed into clinical trials to date. This could be attributed to the high cost of inhaled regimes due to the expensive production and characterisation of the nanoparticles as well as the need for an inhalation device as compared to the oral treatment. Another barrier could be the lack of medical acceptance due to insufficient number of trained staff to educate the patients on the correct usage of the inhalation device. Hence, these barriers should be addressed satisfactorily to make the inhaled nanoparticles regimen a reality for the treatment of TB.

Keywords:

• Nanoparticles
• inhalation
• tuberculosis
• device

Acknowledgments

Authors would like to thank Fundamental Research Grant Scheme, Ministry of Higher Education Malaysia for their financial support. We acknowledge Universiti Sains Malaysia for providing access to various journals to gather information to compile this review article.

Author contributions

Sowmya Ramachandran: writing & editing. Priyanka Prakash: writing & editing. Noratiqah Mohtar: writing, review & editing. K Sudesh Kumar: funding acquisition, review & editing. Thaigarajan Parumasivam: funding acquisition, writing, review & editing.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Table 1. Summary of inhalable nano-formulations of anti-tubercular drugs with their key findings from the year 2018 to 2023.

Additional information

Funding

This work was supported by Ministry of Higher Education Malaysia [frgs/1/2018/skk09/usm/03/1].