Investigating the Impact of First-Line Anti-Tuberculosis Drugs Encapsulated in a Eugenol-Based Nanoemulsion on Human Serum Albumin.

BACKGROUND: Eugenol exhibits broad-spectrum antibacterial and anti-inflammatory properties. However, cytotoxicity at high concentrations limits the full utilization of eugenol-based drug complexes. Formulations of multidrug-loaded eugenol-based nanoemulsions have reduced cytotoxicity; however, it remains crucial to understand how these eugenol complexes interact with primary human carrier proteins to design and develop therapeutic alternatives. Consequently, this study primarily aims to investigate the impact on Human Serum Albumin (HSA) when it interacts with eugenol-based complexes loaded with first-line anti-tuberculosis drugs. METHODS: This study used various spectroscopic such as UV-visible spectroscopy, Fluorescence spectroscopy, Fourier-transform infrared spectroscopy and computational methods such as molecular docking and 100 ns molecular simulation to understand the impact of eugenol-based first-line anti-tuberculosis drug-loaded nanoemulsions on HSA structure. RESULTS: The binding of the HSA protein and eugenol-based complexes was studied using UV-visible spectroscopic analysis. Minor changes in the fluorophores of the protein further confirmed binding upon interaction with the complexes. The Fourier-transform infrared spectra showed no significant changes in protein structure upon interaction with eugenol-based multidrug-loaded nanoemulsions, suggesting that this complex is safe for internal administration. Unlike eugenol or first-line anti-tuberculosis alone, molecular docking revealed the strength of the binding interactions between the complexes and the protein through hydrogen bonds. The docked complexes were subjected to a 100 ns molecular dynamics simulation, which strongly supported the conclusion that the structure and stability of the protein were not compromised by the interaction. CONCLUSIONS: From the results we could comprehend that the eugenol (EUG)-drug complex showed greater stability in HSA protein structure when compared to HSA interacting with isoniazid (INH), rifampicin (RIF), pyrazinamide (PYR), or ethambutol (ETH) alone or with EUG alone. Thus, inferring the potential of EUG-based drug-loaded formulations for a safer and efficient therapeutic use.

Multi-drug loaded eugenol-based nanoemulsions for enhanced anti-mycobacterial activity.

Tuberculosis is one of the oldest bacterial infections known to mankind caused by Mycobacterium tuberculosis. The aim of this research is to optimize and formulate a multi-drug loaded eugenol based nanoemulsion system and to evaluate its ability as an antimycobacterial agent and its potential to be a low cost and effective drug delivery system. All the three eugenol based drug loaded nano-emulsion systems were optimized using response surface methodology (RSM)-central composite design (CCD) and were found stable at a ratio of 1 : 5 (oil : surfactant) when ultrasonicated for 8 minutes. The minimum inhibitory concentration (MIC) values against strains of Mycobacterium tuberculosis highly proved that these essential oil-based nano-emulsions showed more promising results and an even improved anti-mycobacterium activity on the addition of a combination of drugs. The absorbance of 1st line anti-tubercular drugs from release kinetics studies showed a controlled and sustained release in body fluids. Thus, we can conclude that this is a much more efficient and desirable method in treating infections caused by Mycobacterium tuberculosis and even its MDR/XDR strains. All these nano-emulsion systems were stable for more than 3 months.