Chitosan-Glycerol Injectable Hydrogel for Intratumoral Delivery of Macromolecules

Area of Science:

• Biomaterials Science
• Drug Delivery
• Oncology

Background:

• Intratumoral injection of biologics and immunotherapeutics offers advantages over systemic delivery for cancer treatment.
• Poor retention of injected therapeutics within the tumor microenvironment due to high interstitial pressure and dense architecture limits efficacy.
• Injectable hydrogels can serve as viscoelastic vehicles to improve therapeutic retention and control release.

Purpose of the Study:

• To develop and characterize a chitosan-glycerol hydrogel for enhanced intratumoral delivery of macromolecules.
• To evaluate the injectability, biocompatibility, retention, and release properties of the developed hydrogel.

Main Methods:

• A chitosan-glycerol hydrogel was synthesized and its gelation parameters and mechanical properties were characterized.
• Injectability through a 27-gauge needle was assessed.
• In vitro biocompatibility was evaluated using standard assays.
• Tumor retention studies were performed using model therapeutics compared to low-viscosity solutions.
• In vitro release kinetics of model therapeutics with varying molecular sizes were investigated.

Main Results:

• The chitosan-glycerol hydrogel exhibited shear-thinning properties, enabling injection through a fine-gauge needle.
• The hydrogel was found to be nontoxic in biocompatibility studies.
• Formulation with the hydrogel significantly improved the retention of model therapeutics within the tumor microenvironment compared to controls.
• Sustained release of model therapeutics across a range of molecular weights was observed from the hydrogel.

Conclusions:

• The developed chitosan-glycerol hydrogel is injectable, biocompatible, and effectively enhances the retention of macromolecules in the tumor microenvironment.
• The hydrogel facilitates sustained release of therapeutics, indicating its potential as a delivery vehicle for intratumoral cancer therapies.