SHetA2 Dry Powder Aerosols for Tuberculosis: Formulation, Design, and Optimization Using Quality by Design

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery
• Pulmonary Medicine

Background:

• Tuberculosis (TB) treatment faces challenges due to complex regimens, side effects, and emerging drug resistance.
• Novel therapeutic strategies are crucial to combat the global TB epidemic.
• SHetA2, an anticancer agent, shows activity against Mycobacterium tuberculosis (MTB) with low toxicity.

Purpose of the Study:

• To develop a dry powder formulation of SHetA2 for pulmonary delivery.
• To overcome SHetA2's poor aqueous solubility and enhance lung concentration.
• To optimize SHetA2 microparticles (MPs) for targeted delivery to alveolar macrophages.

Main Methods:

• Quality by Design (QbD) methodology was employed to create and optimize SHetA2 MPs.
• Three formulations (SHetA2 alone, SHetA2 PLGA, SHetA2 mannitol) were prepared.
• Physicochemical properties, aerosol performance (using Aerolizer DPI), and dissolution rates were evaluated.

Main Results:

• Optimized SHetA2 MPs exhibited spherical morphology (1-3 μm) suitable for alveolar delivery.
• High fine particle fractions (FPF > 77%) were achieved, indicating efficient lung deposition.
• Spray drying converted crystalline SHetA2 to an amorphous form, significantly enhancing solubility and dissolution rate.

Conclusions:

• The developed SHetA2 microparticle formulations demonstrate favorable physicochemical and aerodynamic properties for pulmonary delivery.
• Enhanced solubility and dissolution rates suggest improved therapeutic efficacy for lung TB.
• This approach offers a promising strategy to improve TB treatment by utilizing an anticancer compound with a favorable safety profile.