Dodecenylsuccinic anhydride modified chitosan hydrogels for the sustained delivery of hydrophobic drugs. The case of thymol buccal delivery

Chitosan polymer as a bioactive carrier has an emerging importance due to its great versatility. Many strategies are reported for enhancing its properties. Herein, chitosan hydrogels modified by dodecenylsuccinic anhydride (DDSA) are prepared, characterized by SEM, FTIR, C-13 NMR while their mechanical properties and cytotoxicity are assessed. Chitosan modification was studied by FTIR and C-13 NMR. According to rheological measurements, modified chitosan hydrogels present a predominantly elastic behavior and exert a higher compressive strength than chitosan hydrogels. Furthermore, this work evaluates thymol incorporation, its release profile as well as its in vivo performance in a periodontitis rat model. In vitro studies reveal that thymol-loaded-DDSA-chitosan hydrogels possess antimicrobial activity against Staphylococcus aureus and Pseudomonas aeruginosa for 2 days and antioxidant activity for 5 days. The incorporation of hydrophobic chains improves thymol release profile; however, DDSA-chitosan hydrogels cytotoxicity is greater when compared to chitosan hydrogels. Finally, in a preliminary in vivo study, the local application of thymol-loaded hydrogels is evaluated during a one-week period. The histomorphometric measurements indicate that periodontal damage is lower when thymol is administrated in chitosan hydrogels in comparison to DDSA-chitosan hydrogels. Nevertheless, DDSA-chitosan hydrogels could still be useful for the sustained local delivery of hydrophobic drugs.