Leukocyte Esterase-Activated Nanoconjugates Enables Precise Local Therapy of Ulcerative Colitis via Inflamed...

Area of Science:

• Biomedical Engineering
• Drug Delivery Systems
• Gastroenterology

Background:

• Ulcerative colitis (UC) involves colonic inflammation.
• Leukocyte esterase (LE) is upregulated in inflamed tissues.
• Targeted drug delivery can improve UC therapy.

Purpose of the Study:

• Develop LE-activated nanoconjugates for precise UC treatment.
• Enable inflamed tissue-selective drug delivery.
• Utilize LE as an enzymatic trigger for drug release.

Main Methods:

• Conjugated dexamethasone (DEX) to poly(lactide-co-glycolide) (PLGA) forming DPNCs.
• Utilized the epithelial enhanced permeability and retention (eEPR) effect for accumulation.
• Tested DPNCs in a dextran sulfate sodium-induced colitis model.

Main Results:

• DPNCs showed suppressed drug release during transit.
• Nanoconjugates accumulated in inflamed colonic tissues.
• Oral DPNCs improved colonic drug accumulation and therapeutic outcomes compared to free DEX.
• Minimized systemic drug distribution was observed.

Conclusions:

• LE-activated nanoconjugates offer a promising oral platform for UC.
• This strategy enables precise and safe local therapy for UC.
• Targeting LE activity can enhance therapeutic efficacy in colitis.