Dan Luo, Yu Wang, Dan Zhou, Shiyan Wang, Mengran Guo
Drug delivery systems have long faced a fundamental challenge: achieving high drug-loading efficiency, precise control over release, and in vivo safety simultaneously is a difficult task. Cellulose and its derivatives are abundant and renewable, exhibiting good biocompatibility, which makes them promising candidates for drug delivery materials. Representative derivatives, such as carboxymethyl cellulose, hydroxypropyl methyl cellulose, and ethyl cellulose, as well as nanocellulose, including cellulose nanocrystals, cellulose nanofibrils, and bacterial nanocellulose, have enabled the development of diverse carrier formats, including hydrogels, aerogels, films, and particulate systems. Recent advances include pH-responsive bacterial nanocellulose/carboxymethyl cellulose hydrogels for oral ibuprofen delivery, carboxylated nanocellulose/polyethylene glycol/β-cyclodextrin composite aerogels for gastric-selective release of imatinib, and hydroxypropyl methyl cellulose-based microneedle patches for transdermal co-delivery of sumatriptan succinate and naproxen sodium. These examples highlight how cellulose-based systems can be engineered for site-selective delivery, sustained release, and multi-stimuli responsiveness. In this review, we summarize the structural features of cellulose derivatives and nanocellulose, discuss the design principles and release mechanisms of representative delivery platforms, and outline current challenges in manufacturability, safety evaluation, and clinical translation.