School of Chemical Engineering and Technology, North University of China Taiyuan, Shanxi, China.
Department of Chemical and Biological Engineering, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
J Biomater Sci Polym Ed. 2021 Apr;32(6):799-812. doi: 10.1080/09205063.2020.1870258. Epub 2021 Jan 17.
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.
叶酸修饰的羧甲基壳聚糖（FCMC）是通过叶酸作为靶向基团并将叶酸连接到羧甲基壳聚糖上来制备的，然后，通过碳酸钙在 FCMC 溶液中的自组装形成靶向 FCMC/CaCO 杂化纳米球。通过傅里叶变换红外光谱、X 射线衍射分析、BET 测量和热重分析（TGA）研究了纳米球的物理化学性质。结果表明，FCMC/CaCO 杂化纳米球由方解石、球霰石和多糖组成，有机化合物的含量为 12.17%。此外，还分析了杂化纳米球的结构性能。同时，还以二甲双胍（MET）为模型药物分析了杂化纳米球对包封效率、载药量和释放行为的影响。扫描电子显微镜、Zeta 电位分析和紫外-可见分光光度计用于表征杂化纳米球。在 FCMC/Ca 摩尔比为 4:1 和反应 24 h 的条件下，得到的结果表明，获得了具有规则形态的球形聚集体，纳米球的平均粒径为 207 nm。杂化纳米球的比表面积为 27.06 m·g，样品的平均孔径为 3.84 nm，表明样品中存在中孔结构。这种介孔结构可为抗癌药物的吸附提供潜在空间。此外，纳米粒子的表面电荷为正，包封效率为 83.32%。杂化纳米球具有有效的 pH 敏感性控制药物释放能力。所有载药杂化纳米球在 pH 7.4 下均能持续释放 MET，6 天内仅释放约 44.58%的药物。而在酸性条件（pH 5.0）下，药物释放明显加速，超过 98.85%的药物释放。杂化纳米球表现出优异的智能药物输送行为。
