Formation, microstructure, biodistribution and absence of toxicity of polymeric micelles formed by N-octyl-N,O-carboxymethyl chitosan

In this study, N-octyl-N,O-carboxymethyl chitosans (octyl-CM-Chitosan) with different molecular weights and degrees of alkylation were synthesized. The critical micelle concentration of octyl-CM-Chitosan was in the range of 7.5–30.4 mg/L, depending on their chemical compositions. Micelles formed by octyl-CM-Chitosan were spherical, with a particle size of <200 nm and high negative zeta potentials of ∼30 mV. Additionally, multi-core microstructure of octyl-CM-Chitosan micelle was confirmed by using fluorescence quenching technique. With the decrease of molecular weight and increase of alkylation, both of the hydrophobicity of inner-core and aggregation number of alkyl chains per microdomain increased. Fluorescein-labeled octyl-CM-Chitosan micelles could easily avoid the mononuclear phagocyte system (MPS) clearance and had the potential for passive targeting to non-MPS tissues. The absence of toxicity of octyl-CM-Chitosan micelles as intravenous materials was confirmed by hemolysis, cell viability assays and histopathological evaluations. These results suggest that octyl-CM-Chitosans are promising materials for intravenous administration.