Self-Assembly Behavior and Doxorubicin-Loading Capacity of Acylated Carboxymethyl Chitosans

Abstract

A new type of acylated carboxymethyl amphiphilic chitosan (ACC) with the use of acyl chain of varying lengths, from C(2) to C(12), and various degrees of acyl substitution was successfully synthesized and has been characterized in terms of its self-assembly behavior, structural stability, and drug encapsulation. The resulting nanostructure of the ACC nanoaggregates can be well manipulated through a control of hydrophobicity. Structural evolution of the self-assembled nanoaggregates is extensively characterized via (1)H NMR, FTIR, DSC, and TEM. A critical value of the hydrophobic effect, (X(DH) x X(Cn)), i.e., a product of "degree of acyl substitution" and "carbon number of acyl chain", can be employed as an indicator for structural variation of the natioaggregates: when (X(DH) x X(Cn)) exceeded 1.5, the architecture of the nanoaggregates underwent a structural transformation from solid nanoparticle to hollow nanocapsules. The nanoaggregates exhibited an excellent colloidal and structural stability in aqueous medium. An improved affinity toward drug encapsulation, i.e., doxorubicin, can be technically designed according to the amphiphilic nature of the resulting nanoaggregates for drug delivery.