Two Modes of Associations of Curcumin with Pre- and Nanoaggregated Chitosan Oligosaccharide Lactate: Ionic Strength and Hydrophobic Bile Salt Modulate Partition of Drug and Self-Assembly Process

Abstract

Chitosan oligosaccharide lactate (COL) has been modified to improve water solubility of chitosan, especially for the uses in drug delivery and biomedical applications. The present study reveals that self-assembly of COL in solution forms nanoaggregates of size 10–30 nm with a critical aggregation concentration (cac) of ∼5 μM. Fluorescence quenching of pyrene establishes that one COL chain may form around five independent hydrophobic microdomains during self-assembly in solution that are crucial to drug–polymer contact. Interaction of COL with a representative hydrophobic drug molecule, curcumin, implies two different kinds of binding mechanisms of curcumin with the pre- and nanoaggregated forms of COL, respectively. A strong ground state interaction between curcumin and nanoaggregated COL has been noted with an association constant of 3.91 × 104 L/mol at 298 K. This association has been found to be diffusion controlled, enthalpy driven, and as consequences of hydrophobic effects due to van der Waals inter...