Active Principal Ingredient (API) encapsulation through adsorption and physical entrapment onto TEMPO-oxidized cellulose nanofibrils (toCNFs) is possible, but challenges such as burst release and use of low water-soluble API such as sulfadiazine (SD) are yet to be addressed. The objective of this study is to assess the release property and antibacterial activity of toCNF/β-Cyclodextrin (β-CD)/SD materials in the form of films. Release in sink conditions was achieved with result highlighting the importance of the toCNF network structure, which is tightened at acidic pH for toCNFs due to its carboxylic content, reducing the burst effect phenomena. Antibacterial activity against Staphylococcus aureus and Escherichia coli was assessed and the results showed a clear beneficial impact of using β-CDs. An antibacterial effect for toCNF/SD films is confirmed for 3 successive applications whereas an antibacterial effect for a toCNF/CMβCD/SD film is prolonged up to 7 successive applications. The improvement of the topical release of a prophylactic agent with these materials are making them promising for biomedical applications such as wound dressing.