COX-2 inhibitor delivery system aiming intestinal inflammatory disorders

Area of Science:

• Biomaterials Science
• Pharmacology
• Gastroenterology

Background:

• Selective COX-2 inhibitors like etoricoxib (ETX) show potential for intestinal inflammatory disorders.
• Systemic administration of ETX causes off-site effects, reducing local therapeutic efficacy.
• A novel drug delivery system (DDS) is needed to enhance local ETX delivery and minimize side effects.

Purpose of the Study:

• To develop and evaluate an electrospun fibrous mesh (eFM) based DDS for local delivery of etoricoxib (ETX).
• To assess the safety and efficacy of the ETX-loaded eFMs in a preclinical model relevant to colorectal diseases.

Main Methods:

• Etoricoxib (ETX) was loaded into electrospun fibrous meshes (eFMs) at varying concentrations (1, 2, and 3 mg mL⁻¹).
• The morphology and mechanical properties of the drug delivery system (DDS) were analyzed.
• In vitro drug release kinetics were studied over 36 hours.
• Cytotoxicity assays were performed on human colonic epithelial and fibroblast cells.
• The effect of the DDS on inflammatory marker secretion (PGE₂, IL-8, TNF-α) in stimulated human macrophages was evaluated.

Main Results:

• The eFMs maintained their structural integrity and mechanical properties after ETX loading.
• ETX exhibited a burst release within 12 hours, followed by sustained release up to 36 hours.
• The tested concentrations of ETX were non-toxic to human colonic cells.
• The DDS loaded with the highest ETX concentration significantly reduced PGE₂, IL-8, and TNF-α secretion in stimulated macrophages.

Conclusions:

• The proposed electrospun fibrous mesh DDS provides a safe and effective platform for local ETX delivery.
• This DDS has the potential to treat colorectal diseases associated with COX-2 mediated inflammation.
• The localized delivery approach circumvents systemic side effects and enhances therapeutic outcomes.