Nano-Based Drug Delivery Systems of Potent MmpL3 Inhibitors for Tuberculosis Treatment

Area of Science:

• Pharmaceutical Sciences
• Nanotechnology
• Infectious Diseases

Background:

• Tuberculosis (TB) is a major global health threat, causing millions of deaths annually.
• Current TB treatment faces challenges including drug toxicity, poor bioavailability, and low patient adherence, leading to drug resistance.
• Developing effective drug delivery systems is crucial for overcoming these treatment limitations.

Purpose of the Study:

• To develop and characterize novel nanocarrier formulations for enhanced delivery of antimycobacterial compounds.
• To evaluate the physicochemical properties and in vitro antimycobacterial activity of nanoemulsions (NEs) and niosomes (NIs) loaded with MmpL3 inhibitors.
• To identify a superior nanocarrier system for improved tuberculosis therapy.

Main Methods:

• Preparation and characterization of nanoemulsions (NEs) and niosomes (NIs) loaded with MmpL3 inhibitors BM635 and BM859.
• Physicochemical characterization included hydrodynamic diameter, ζ-Potential, polydispersity index (PDI), drug-entrapment efficiency, polarity, and microviscosity.
• Antimycobacterial activity was assessed against Mycobacterium tuberculosis, determining the minimum inhibitory concentration (MIC).

Main Results:

• Both NEs + BM635 and NIs + BM859 formulations exhibited favorable physicochemical properties and stability.
• Niosomes loaded with BM859 (NIs + BM859) demonstrated potent antimycobacterial activity against M. tuberculosis, with a MIC of 0.6 µM.
• The enhanced activity of NIs + BM859 is attributed to the higher aqueous solubility and easier diffusion of BM859 compared to the hydrophobic BM635.

Conclusions:

• Niosomal formulation of BM859 is a promising nanocarrier for tuberculosis treatment, showing superior antimycobacterial efficacy compared to the free drug.
• The physicochemical properties and drug loading efficiency support the potential of this niosomal system for therapeutic applications.
• Further in vivo studies are warranted to fully evaluate the therapeutic potential of the NIs + BM859 formulation for tuberculosis.