Controlled Release Subcutaneous Tramadol‐Loaded Silk Fibroin Injectable Gel

ABSTRACT Pain relievers, such as tramadol, are essential in treating chronic pain, which affects up to 20% of adults globally. However, tramadol was frequently administered due to its short half‐life, resulting in a high dependence on the patient's compliance. This study presents controlled release subcutaneous tramadol‐loaded silk fibroin injectable gel, a novel drug delivery system which gradually releases the medication, in order to achieve minimum side effects, enhanced efficacy, and reduced dosing. The 1%, 1.5%, and 2% silk fibroin hydrogels encapsulating tramadol were successfully fabricated using the sonication technique with a suitable gelation time of 40–90 min. The hydrogels exhibited excellent in vitro and ex vivo injectability, retained stability with preserved chemical integrity and thermal properties over 1 month. Silk fibroin hydrogel encapsulating tramadol demonstrated in vitro biodegradability of up to 35 days and concentration‐dependent cytotoxicity. A controlled drug release was observed, in which the in vitro drug release was inversely correlated to the silk fibroin concentration of the hydrogel. A rapid initial drug release was observed, indicating diffusion as the primary mechanism. This suggests silk fibroin hydrogel encapsulating tramadol as a novel biodegradable‐controlled release drug delivery system with a potential for implementation in chronic pain treatment.