A pH-sensitive nano drug delivery system derived from pullulan/doxorubicin conjugate

A novel pH-sensitive nanoparticle drug delivery system for doxorubicin (DOX) is prepared. Pullulan, a natural biocompatible polysaccharide, was partly carboxymethylized; hydrazine hydrate was condensed with the carboxyl groups forming hydrazide. The hydrazide was coupled with DOX through the formation of hydrazone bond. The chemical structure of the conjugate was determined by FTIR and (1)H NMR. The pullulan/DOX conjugate nanoparticles were formed through the aggregation of hydrophobic DOX. The size and morphology of prepared nanoparticles were characterized using dynamic light scattering and transmission electron microscope. The results showed that the nanoparticles were spherical and their size was less than 100 nm. The content of DOX in conjugate was 3.18 wt %. The investigation of the release behavior in vitro indicated that the DOX was released from nanoparticles faster at pH 5.0 (62% DOX released within 24 h) than at pH 7.4 (29% DOX released within 24 h). The in vitro cytotoxicity of pullulan/DOX conjugate nanoparticles was tested by the MTT assay.