Antitubercular activity of 7-methyljuglone-loaded poly-(lactide-co-glycolide) nanoparticles

Abstract

Mycobacterium tuberculosis (M. tuberculosis) is a bacterium that causes the highly infectious disease, Tuberculosis (TB). During the 19th and early 20th centuries TB was known as the “white plague” due to the characteristic pallor of the patients infected with the disease. Tuberculosis was a major public health problem causing widespread illness and death. In the mid-20th century, effective treatments for TB were developed which included antibiotics and the Bacille Calmette-Guerin (BCG) vaccine. This led to a sharp decline in TB cases in developed countries such as Australia, Canada, European countries, New Zealand and the United States of America. However, even with the discovery and development of treatments for TB, it remains a main health obstruction in several parts of the world, especially in developing countries with limited access to healthcare. There are numerous reasons why TB as a disease is still problematic in South Africa. These include poor hygiene, overcrowding, poverty, and human immunodeficiency virus (HIV) co-infection. These factors make it difficult for people to access healthcare services and increase the risk of the spread of TB. Additionally, drug-resistant strains of TB have emerged in recent years, which require more complex and expensive treatment regimens.

Medicinal plants have the potential to contribute to the management of drug-resistant strains of TB, it has been utilized for decades and has a major role in traditional usage in the treatment of diseases such as TB. Euclea natalensis A. DC (E. natalensis), is one such medicinal plant that is indigenous to South Africa. 7-Metyhyljuglone (7-MJ), a pure compound isolated from E. natalensis, has been shown to have promising antimycobacterial activity. The pure compound showed minimum inhibitory concentration (MIC) values against Mycobacterium smegmatis (M. smegmatis), drug susceptible M. tuberculosis (H37Rv) and multidrug-resistant M. tuberculosis (MDR11) of 1.6 µg/mL, 0.4 µg/mL and 1.6 µg/mL, respectively. 7-Metyhyljuglone has however also been shown to be highly cytotoxic as it exhibited a 50% inhibitory concentration (IC50) of 3.25 µg/mL on differentiated macrophage-like human histiocytic lymphoma (U937) cells.

Literature indicated that using poly-(lactide-co-glycolide) (PLGA) nanoparticle formulations, as a delivery system, have shown the potential to reduce the toxicity of known toxic compounds. Therefore, this study aimed to determine whether PLGA nanoparticles containing 7-MJ, may have effective antimycobacterial properties, whilst being less cytotoxic than 7-MJ-only. This study found that the 7-MJ PLGA nanoparticles showed some antimycobacterial activity as they exhibited an MIC value of 125 µg/mL against M. smegmatis and MIC values of 250 µg/mL against both strains of M. tuberculosis (H37Rv and MDR11). The 7-MJ PLGA nanoparticles also showed to decrease the cytotoxic effect of 7-MJ on differentiated macrophage-like U937 cells with an IC50 of 247.17 µg/mL.

Furthermore, this study is the first to report that the synthesized 7-MJ PLGA nanoparticles were successfully taken up within differentiated macrophage-like U937 cells, the cells which are most infected by M. tuberculosis.