Synthesis and self-assembly behavior of decyl alginate ester derivative via bimolecular nucleophilic substitution reaction

Due to the presence of abundant carboxyl and hydroxyl groups on the molecular chain, the raw alginate is too hydrophilic to achieve effective entrapment and controlled release of hydrophobic drug. To broaden the application range of alginate, 1-bromodecane was covalently grafted onto sodium alginate (SA) via bimolecular nucleophilic substitution (S N 2) reaction to synthesize decyl alginate ester derivative (DAED). The structure and self-assembly behavior of DAED were characterized by means of FT-IR, 1 H NMR, thermogravimetric analysis (TGA), XRD, fluorescence spectrum (FM), surface tension (SFT), TEM, atomic force microscope (AFM), and dynamic light scattering (DLS). Furthermore, the loading and in vitro release of hydrophobic ibuprofen for the self-assembled DAED microcapsules and their cytotoxicity against the murine macrophage RAW264.7 cell were investigated. The FT-IR and 1 H NMR analyses showed that the decyl groups were successfully grafted onto the alginate backbone. The results of TGA and XRD showed that due to the grafting decyl side chains, the intramolecular hydrogen bond of DAED was broken, thus resulting in the decrease of its thermal stability and the change of its microcrystalline structure, which improved its molecular flexibility and self-assembly behavior. Therefore, the DAED could reveal good amphiphilic property with the critical aggregation concentration (CAC) of 0.08 g/L, and form micelle-like aggregates with the average hydrodynamic diameter of 185.1 nm (PDI = 0.615) and zeta potential at about −39.2 mV. In addition, from TEM and AFM observation, DAED could generate spherical drug-loaded microcapsules through its self-assembly behavior, which exhibited excellent sustained-release property ascribed to the enhanced affinity of DAED to hydrophobic ibuprofen. And the prepared DAED microcapsules also displayed low cytotoxicity to the murine macrophage RAW264.7 cells. Therefore, it was the good self-assembly behavior of DAED that made it have great potentials as the hydrophobic drug carriers in pharmaceutical field.