Chitosan for enhanced intestinal permeability: prospects for derivatives soluble in neutral and basic environments

Area of Science:

• Biomaterials Science
• Pharmacology
• Cell Biology

Background:

• Chitosan derivatives are explored for drug delivery applications.
• Understanding their effect on intestinal epithelial permeability is crucial for therapeutic efficacy.

Purpose of the Study:

• To investigate the impact of chitosan hydrochloride and chitosan glutamate on Caco-2 cell monolayer integrity and permeability.
• To evaluate the efficacy of these chitosan salts as absorption enhancers in acidic versus neutral environments.

Main Methods:

• Caco-2 cell monolayers were treated with varying concentrations of chitosan salts (0.5% and 1.5% w/v) at pH 6.2 and 7.4.
• Transepithelial electrical resistance (TEER) was measured to assess monolayer integrity.
• Permeability was quantified using the radioactive marker [14C]-mannitol transport.

Main Results:

• Chitosan salts significantly reduced TEER and increased [14C]-mannitol permeability at pH 6.2, indicating enhanced absorption.
• Chitosan glutamate (1.5%) reduced TEER by 70%, and chitosan hydrochloride (1.5%) by 77%.
• At pH 7.4, chitosan salts were insoluble and showed no significant effect on TEER or mannitol transport.

Conclusions:

• Chitosan hydrochloride and chitosan glutamate act as potent absorption enhancers in acidic environments.
• The insolubility of these chitosan salts at neutral/basic pH limits their utility for drug delivery in the colon.
• Development of more soluble chitosan derivatives is needed for effective delivery in the large intestine.