Metal cations-mediated loading of tetracycline on cellulose nanocrystals

•TCH formed a complex with CNC in different interaction conditions.•The 1-hour incubation time had the highest encapsulation efficiency.•The higher the CNC content, the more CNC-TCH complex formation.•Divalent cations such as Mg+2 and Ca+2 can remarkably increase the complexation ability of CNC −TCH. The effect of different parameters on the complex formation of tetracycline hydrochloride (TCH), a cationic drug, with cellulose nanocrystal (CNC) as drug carriers was investigated. The encapsulation efficiency (EE) of the drug on TCH-CNC complexes was remarkably influenced by incubation time and weight ratios of the compositions. However, the physical bindings of the complexes in water were very weak. Employing divalent metal cations such as Mg2+ and Ca2+ as chelating agents in TCH-CNC complex formulation, resulted in a significant increase in EE. The results proved that by tailoring the interaction conditions of the complexes, the drug can be more efficiently loaded on the nanocarriers.