Cubosome Lipid Nanocarriers As a Drug Delivery Vehicle for Intracellular Mycobacterium tuberculosis Infections

Abstract

Mycobacterium tuberculosis (MTB) causes the infectious disease tuberculosis (TB), responsible for more deaths than any other single infectious disease in history. Intracellular MTB are slow growing and difficult to target with traditional antitubercular drugs, leading to the emergence of multidrug resistance in TB infection, which is a major global public health issue. Recent advances in innovative lipid nanotechnologies for drug delivery have demonstrated promising outcomes for chronic infectious diseases but have not yet been tested as potential delivery systems for intracellular infections such as TB. The current study evaluates the potential of monoolein (MO)-based cationic cubosomes for the encapsulation and delivery of the first line antitubercular drug rifampicin (RIF) against an MTB-H37Ra in vitro culture model. In particular, we show that the use of cationic cubosomes as delivery vehicles reduced the minimum inhibitory concentration (MIC) of RIF by 2-fold against actively replicating MTB-H37Ra (compared to that of the free drug) and also shortened the lifecycle duration of axenic MTB-H37Ra from 5 to 3 days. The cubosome-mediated delivery was also found to be effective against intracellular MTB-H37Ra within THP-1 human macrophages, with a 2.8 log reduction in viability of the bacilli after 6 days incubation at the MIC. The killing time was also reduced from 8 to 6 days without distressing the host macrophages. Mechanistic studies on the uptake of RIF-loaded cationic cubosomes using total internal reflection fluorescence microscopy (TIRFM) demonstrated the capacity of these lipid particles to effectively target intracellular bacteria. Overall, these results demonstrate that cationic cubosomes are a potent delivery system for the antitubercular drug RIF for therapeutic management of TB.

Advanced drug delivery and therapeutic strategies for tuberculosis treatment

“…Among them, drug carriers made of modified mannose are the most common and can be added to liposomes, SLN, and polymer micelles [255][256][257] Studies have shown that cubosomal lipid nanocarriers exhibit higher drug delivery efficiency as well as bioavailability than conventional formulations. They are not only effective against free bacilli but also have the ability to deliver drugs to intracellular bacilli [258]. Thus, the identification of better sets of ligands with higher binding affinity for macrophage-based receptors might result in enhanced targeting efficiency.…”

Celecoxib-Loaded Cubosomal Nanoparticles as a Therapeutic Approach for Staphylococcus aureus In Vivo Infection

“…The fusion absorption method described facilitates the effective and expeditious internalization of cubosomes by Gram-negative bacteria, even when they encounter their tough outer membrane. The cubosomal formulations have been utilized in enhancing the antibacterial activity of some antibiotics, including gatifloxacin [ 33 ], erythromycin [ 34 ], and rifampicin [ 35 ].…”