Inhalable Mannosylated Rifampicin-Curcumin Co-Loaded Nanomicelles with Enhanced In Vitro Antimicrobial Efficacy for...

Area of Science:

• Nanotechnology
• Pharmaceutical Sciences
• Infectious Diseases

Background:

• Tuberculosis (TB) remains a leading cause of death from infectious diseases globally.
• Targeted drug delivery to the lungs is crucial for treating pulmonary TB, particularly for reaching alveolar macrophages where Mycobacterium tuberculosis resides.

Purpose of the Study:

• To develop and evaluate a mannose-decorated nanocarrier system for co-encapsulating rifampicin and curcumin for pulmonary tuberculosis therapy.
• To assess the formulation's physicochemical properties, lung deposition, and in vitro and in vivo efficacy.

Main Methods:

• Development of mannose-decorated polymeric micelles using Soluplus® to encapsulate rifampicin and curcumin.
• Characterization of micellar size, stability, and drug loading.
• In vitro nebulization studies for lung deposition assessment.
• In vivo biodistribution studies using radiolabeled micelles.
• Evaluation of microbicidal efficacy against Mycobacterium tuberculosis H37Rv.

Main Results:

• Mannose-decorated micelles exhibited optimal colloidal properties (~108 nm) and stability in simulated lung fluid.
• Nebulization studies confirmed suitability for deep lung delivery, supported by in vivo lung accumulation data.
• The nanoformulation showed no hemolytic activity.
• Mannose decoration significantly enhanced microbicidal efficacy by 5.2-fold compared to mannose-free micelles.

Conclusions:

• The novel inhaled nanoformulation demonstrates potential for targeted delivery of anti-TB drugs to the lungs.
• Mannose decoration enhances the therapeutic efficacy of co-loaded rifampicin and curcumin against pulmonary tuberculosis.
• This approach offers a promising strategy for improving the treatment of tuberculosis.