Development and Optimization of Myricetin Loaded Inhalable Microsphere to Treat COPD.

Area of Science:

• Pharmaceutics
• Drug Delivery
• Respiratory Medicine

Background:

• Chronic Obstructive Pulmonary Disease (COPD) requires effective and sustained drug delivery for improved patient outcomes.
• Pulmonary drug delivery systems aim to enhance therapeutic efficacy and reduce systemic side effects.
• Myricetin, a natural flavonoid, possesses potential therapeutic properties for respiratory conditions.

Purpose of the Study:

• To develop and optimize inhalable microspheres loaded with myricetin for sustained pulmonary delivery.
• To evaluate the physicochemical, in vitro release, and aerodynamic properties of the myricetin-loaded microspheres.
• To assess the bronchodilatory activity of the optimized formulation in a preclinical model.

Main Methods:

• Myricetin-loaded microspheres were prepared using gellan gum and sodium alginate via ionotropic gelation and a 3^2 full factorial design.
• Characterization included particle size, morphology, entrapment efficiency, zeta potential, in vitro drug release, and aerodynamic performance (twin impinger).
• Stability studies were conducted under accelerated and real-time conditions. Bronchodilatory activity was assessed using a goat tracheal chain model and compared to theophylline anhydrous.

Main Results:

• The optimized formulation (DF4) showed spherical morphology, optimal particle size (7.72 μm), high entrapment efficiency (72.84%), and good colloidal stability (negative zeta potential).
• Excellent aerodynamic properties (FPF 31.71%), sustained release over 12 hours, and remarkable stability over 6 months were observed.
• Significant bronchodilatory activity (63.47% relaxation at 25 μg/ml) was achieved, with efficacy approximately 80.8% compared to theophylline anhydrous.

Conclusions:

• Optimized myricetin-loaded inhalable microspheres represent a promising pulmonary delivery system for COPD management.
• The formulation offers sustained release, improved lung deposition, and significant bronchodilatory effects, potentially reducing dosing frequency and enhancing patient compliance.
• Further in vivo studies are warranted to support clinical translation for improved therapeutic outcomes in COPD patients.