Chitosan ascorbate: a chitosan salt with improved penetration enhancement properties

Area of Science:

• Biomaterials Science
• Drug Delivery
• Polymer Chemistry

Background:

• Chitosan is a versatile biopolymer with potential in drug delivery due to its mucoadhesive and permeation-enhancing properties.
• Modifying chitosan through salification can alter its physicochemical characteristics and biological interactions.
• Developing effective and safe delivery systems for enhanced drug absorption across mucosal barriers remains a significant challenge.

Purpose of the Study:

• To evaluate the penetration enhancement capabilities of chitosan ascorbate compared to chitosan hydrochloride and chitosan lactate.
• To assess the efficacy of chitosan salts in facilitating the transport of a model hydrophilic molecule across buccal and intestinal cell models.
• To determine the cytotoxicity of chitosan ascorbate on Caco-2 cells.

Main Methods:

• Three different grades of chitosan were salified with ascorbic acid, hydrochloric acid, and lactic acid.
• The penetration enhancement properties of the resulting chitosan salts were investigated using porcine buccal mucosa and Caco-2 cell monolayers.
• Fluorescein isothiocyanate-dextran (FD4), a high molecular weight hydrophilic molecule, was used as a model penetrant.
• Cytotoxicity was assessed on Caco-2 cells.

Main Results:

• Chitosan ascorbate exhibited superior penetration enhancement effects on both buccal porcine mucosa and Caco-2 cell monolayers compared to chitosan hydrochloride and chitosan lactate.
• The model penetrant FD4 showed significantly increased permeation in the presence of chitosan ascorbate.
• Cytotoxicity assays revealed that chitosan ascorbate possesses a safety profile comparable to chitosan hydrochloride and lactate.

Conclusions:

• Salification of chitosan with ascorbic acid yields a derivative with enhanced penetration-enhancing properties for mucosal drug delivery.
• Chitosan ascorbate represents a promising alternative for improving the absorption of hydrophilic drugs across buccal and intestinal epithelia.
• The comparable cytotoxicity suggests chitosan ascorbate is a safe excipient for pharmaceutical formulations targeting mucosal surfaces.