Development of Carboxymethyl Cellulose-Gelatin Aerogels for Urea Delivery

Urea is an effective therapeutic agent for the treatment of chronic hyponatremia; however, its high water solubility leads to rapid dissolution, limiting sustained therapeutic efficacy and patient compliance. This study aimed to develop and evaluate controlled-release urea delivery systems using biopolymer-based aerogel and xerogel matrices. Urea-loaded aerogel and xerogel composites were prepared from carboxymethyl cellulose (CMC) and surplus gelatin (GE), crosslinked with varying concentrations of glutaraldehyde (GA). The effects of the CMC:GE ratio and GA concentration on gelation behavior, swelling properties, and urea release kinetics were systematically investigated. Structural and thermal characteristics were analyzed using scanning electron microscopy (SEM), X-ray diffraction (XRD), and differential scanning calorimetry (DSC). The CMC:GE ratio significantly influenced the structural and functional properties of the composites. Among the formulations studied, the aerogel with a CMC:GE ratio of 1:3 and 5% (v/v) GA  xhibited the most effective controlled-release performance, providing a markedly prolonged urea release compared with the corresponding xerogel. XRD and DSC analyses indicated that urea was predominantly present in an amorphous or molecularly dispersed state within the aerogel matrix, with traces of residual crystallinity. SEM observations revealed reduced pore size and increased matrix density following urea loading, indicating a more compact internal structure favorable for sustained release. CMC-GE aerogels crosslinked with GA are promising controlled-release carriers for urea. The optimized 1:3 CMC:GE aerogel demonstrated enhanced swelling and significantly slower urea release than xerogels and medical-grade urea, highlighting its potential for sustained urea delivery.