CD-MOF Based pH/ROS Sensitive 5-ASA Delivery System for Ulcerative Colitis Therapy

Area of Science:

• Materials Science
• Biomedical Engineering
• Pharmacology

Background:

• Ulcerative colitis (UC) treatment is limited by 5-aminosalicylic acid's (5-ASA) poor solubility and gastrointestinal absorption.
• Developing advanced drug delivery systems is crucial for enhancing therapeutic efficacy and patient outcomes in UC management.

Purpose of the Study:

• To engineer a novel cyclodextrin-based metal-organic framework (CD-MOF) carrier (ASA@CM) for 5-ASA.
• To create targeted microspheres (ASA@CM/SL) using sodium alginate/L-arginine complex (SA-LA) for improved 5-ASA delivery to the colon.
• To evaluate the therapeutic efficacy and biosafety of ASA@CM/SL in a mouse model of UC.

Main Methods:

• Fabrication of 5-ASA loaded CD-MOF (ASA@CM) to enhance solubility.
• Incorporation of ASA@CM into SA-LA complex via electrospray to form microspheres (ASA@CM/SL).
• In vitro and in vivo assessment of anti-inflammatory, anti-oxidant, therapeutic effects, cytotoxicity, and organ toxicity in a dextran sulfate sodium-induced UC mouse model.

Main Results:

• ASA@CM/SL effectively improved 5-ASA solubility and protected it from the upper gastrointestinal environment.
• The microspheres demonstrated targeted delivery to the colon, significantly alleviating inflammatory responses and restoring intestinal barrier function in UC mice.
• ASA@CM/SL exhibited excellent therapeutic effects with low cytotoxicity and organ toxicity.

Conclusions:

• The developed ASA@CM/SL microspheres represent a promising strategy for enhancing 5-ASA solubility and colon-targeted delivery for effective UC treatment.
• This approach offers a potential platform for delivering hydrophobic drugs to treat intestinal diseases like UC.