ABSTRACT
The linear polysaccharide λ-carrageenan is the only one among the carrageenans not forming secondary, tertiary, and quaternary structures in the presence of inorganic ions. Chloroquine (CQ) is a well-established antimalaria drug also recently discussed in therapeutics against the COVID-19 pandemic. The interaction of this polysaccharide-ionic drug pair was investigated by combining UV-vis spectrophotometry and atomic force microscopy (AFM) imaging. A decrease of the UV peak assigned to free CQ and the occurrence of isosbestic points indicate the formation of complexes. High-resolution AFM height images revealed an increasing height of the single polysaccharide chains in the random coil state upon addition of CQ, indicating the formation of a secondary structure, followed by higher hierarchical aggregates. The disappearance of higher-ordered structures and the recovery of polysaccharide chains with primary structure were observed by introducing inorganic cations (Na+, K+, Ca2+), replacing the condensed CQ and paving the way to reversible ion-induced drug release.