Folate-modified carboxymethyl chitosan (FCMC) was made by folate acid as targeted group and attaching folate to carboxymethyl chitosan, and then, targeted FCMC/CaCO hybrid nanosphere were formed by self-assembly of calcium carbonate in FCMC solution. The physicochemical properties of the nanospheres were investigated by Fourier transform infrared spectroscopy, X-ray diffraction analysis, Brunauer-Emmett-Teller measurement and thermogravimetric analysis (TGA). The results showed that the FCMC/CaCO hybrid nanospheres were composed of calcite, vaterite and polysaccharides, and the content of organic compounds was 12.17%. Also, the structure performance of the hybrid nanospheres was analyzed. Besides, the effects of the hybrid nanospheres on the encapsulation efficiency, the drug loading content and the release behavior were also analyzed with the metformin (MET) as a model drug. Scanning electron microscope, Zeta potential analysis and UV-Vis were used to characterize the hybrid nanospheres. Under the conditions of FCMC/Ca molar ratio of 4: 1 and reaction for 24 h, the achieved results showed that the spherical aggregates with regular morphology were obtained and the average particle size of the nanospheres was 207 nm. The specific surface area of the hybrid nanosphere is 27.06 m·g and the average pore diameter of the sample is 3.84 nm, indicating the presence of mesoporous structure in the sample. This mesoporous structure can supply potential space for adsorption of anticancer drugs. Additionally, the surface charge of the nanoparticles was positive and the entrapment efficiency was 83.32%. The hybrid nanospheres have a capability of effective pH-sensitivity controlled drug release. All the drug loaded hybrid nanospheres successfully sustained the release of MET at pH 7.4, only about 44.58% of the drug released in 6 days. While under acidic condition (pH 5.0) drug release was significantly accelerated, being over 98.85% of the drug released. The hybrid nanospheres demonstrated an excellent smart drug delivery behavior.
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