Chronic sinusitis, a prolonged inflammation of the sinus cavities, significantly impacts patient quality of life and requires effective, sustained treatment modalities. This study focuses on the development and evaluation of microspheres with mucoadhesion intended for prolonged nasal drug delivery. The microspheres were formulated using a solvent evaporation method, employing biocompatible polymers such as chitosan and alginate to enhance mucoadhesive properties. Details of the microspheres composition involved assessing particle size, surface shape, effectiveness of encapsulation, and in vitro medication release. Additionally, mucoadhesion studies were conducted to evaluate the adherence capability of the microspheres to nasal mucosa. The optimized formulation demonstrated a spherical shape with a mean particle size suitable for superior encapsulation efficiency for nasal delivery, and a controlled release profile over 12 hours. In vitro mucoadhesion tests confirmed strong adhesive properties, suggesting prolonged retention in the nasal cavity. The therapeutic efficacy was assessed using an in vitro chronic sinusitis model, which revealed significant reduction in inflammation and improved mucociliary clearance compared to conventional treatments. These findings indicate that mucoadhesive microspheres are a promising approach for the sustained and targeted delivery of drugs in the treatment of chronic sinusitis, potentially enhancing patient compliance and therapeutic outcomes.