Amphiphilic Celecoxib-Polysaccharide Delivery System for Enhanced Colon-Targeted Colitis Therapy

Area of Science:

• Nanotechnology and Drug Delivery
• Materials Science
• Pharmacology

Background:

• Ulcerative colitis (UC), a chronic inflammatory bowel disease (IBD), requires effective anti-inflammatory treatments.
• Celecoxib (CXB) shows therapeutic potential for UC but suffers from poor solubility and bioavailability.
• Existing oral medications for UC face challenges in efficacy and targeted delivery.

Purpose of the Study:

• To develop a novel chondroitin sulfate A-Celecoxib (CSA-CXB) polymeric nanoprodrug.
• To overcome the limitations of celecoxib's solubility and bioavailability for ulcerative colitis treatment.
• To evaluate the in vitro and in vivo efficacy of the CSA-CXB nanoprodrug in a UC model.

Main Methods:

• Conjugation of celecoxib (CXB) to chondroitin sulfate A (CSA) using succinic anhydride and ethylenediamine.
• Self-assembly of CSA-CXB polymers into nanoparticles in aqueous conditions.
• Assessment of nanoparticle stability, blood compatibility, responsiveness, and in vitro/in vivo UC treatment efficacy.

Main Results:

• CSA-CXB nanoparticles exhibited sustained drug release, with a mean particle size of 188.4 nm.
• In vitro studies showed significant antioxidant and anti-inflammatory effects, reducing ROS, TNF-α, IL-6, NO, and COX-2.
• In vivo studies confirmed efficient colon targeting and mitigation of UC symptoms by inhibiting inflammatory cytokines.

Conclusions:

• The developed CSA-CXB nanoprodrug effectively improves the therapeutic impact of celecoxib for ulcerative colitis.
• This novel nanoprodrug formulation demonstrates potential for enhanced clinical application in UC treatment.
• CSA-CXB offers a promising new strategy for managing ulcerative colitis through targeted drug delivery.