New mesalamine polymeric conjugate for controlled release: Preparation, characterization and biodistribution study

Area of Science:

• Polymer Chemistry
• Drug Delivery Systems
• Gastroenterology

Background:

• Mesalamine (5-ASA) is a first-line treatment for ulcerative colitis but suffers from low bioavailability and poor adherence.
• Existing mesalamine formulations present challenges including systemic adverse events and inconvenient dosing regimens.

Purpose of the Study:

• To synthesize and characterize a new chondroitin sulfate-mesalamine conjugate as an improved drug delivery system for ulcerative colitis.
• To evaluate the in vitro drug release, cytotoxicity, and in vivo biodistribution of the novel conjugate.

Main Methods:

• Synthesis of the chondroitin sulfate-mesalamine conjugate using a carbodiimide conjugating agent.
• Characterization via spectroscopic (UV, ATR-FTIR, XRD, NMR 1H) and thermal (TG/DTG, DSC) analyses.
• In vitro drug release studies at pH 9, cytotoxicity assays on a human monocytic cell line, and in vivo biodistribution using Technetium-99m radiolabeling and scintigraphy.

Main Results:

• Spectroscopic and thermal analyses confirmed the successful conjugation of mesalamine to chondroitin sulfate.
• In vitro release studies showed approximately 40% drug release over 50 hours at pH 9, following Higuchi's model.
• The conjugate exhibited no cytotoxicity and demonstrated sustained presence in the lower gastrointestinal tract for up to 8 hours in vivo, with minimal upper GI uptake.

Conclusions:

• The synthesized polymeric conjugate successfully links mesalamine to chondroitin sulfate, enhancing its properties for ulcerative colitis treatment.
• The conjugate demonstrates desirable mucoadhesive properties in the colon and a favorable biodistribution profile, supporting its potential therapeutic application.