A special flower-like chitosan (CS)/calcium phosphate (CaP) microparticle was fabricated as a novel pH-sensitive carrier for sustained release drug system via a rapid one-pot approach. The CS-tripolyphosphate (TPP) nanocomplexes were firstly prepared through ionotropic gelation. Then, the CS nanocomplexes network acted as the template and inducer for adsorbing the mineralized CaP nanosheets and directing its assembly into the flower-like microparticles. The preparation condition optimized by Box-Behnken design-response surface methodology was achieved with 3.16 mg/ml of CS, 127.22 mg/ml of TPP, and 89.50 mM of CaCl2. The morphologies of the system were observed by scanning electron microscopy (SEM) and transmission electron microscope (TEM), and it showed that the flower-like microparticles with a diameter of 5-7 μm are composed of sheet-like petals with about 40 nm in thickness. And the TEM results showed that the petals consist by nanosheets with the thickness of 2-5 nm. The X-ray diffraction (XRD) results showed that the P/Ca ratio of CS/CaP microparticles is 1.29/1. The in vitro release studies demonstrated well sustained-release properties and pH-sensitive releasing characteristic of CS/CaP microparticles. The drug release mechanism was fitted by Korsmeyer-Peppas model at a pH of 5.8 and 7.4, respectively. The in vitro cell viability research demonstrated the microparticles have no obvious cytotoxicity at the dosages below 500 μg/ml. This work supplied a versatile platform as a novel drug delivery system with excellent pH-sensitive and sustained release performances.

中文翻译：

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壳聚糖/磷酸钙花状微粒作为载药平台的载体。

一种特殊的花状壳聚糖（CS）/磷酸钙（CaP）微粒是一种新型的pH敏感载体，可通过快速一锅法持续释放药物系统。首先通过离子凝胶法制备了CS-三聚磷酸盐（TPP）纳米复合物。然后，CS纳米复合物网络充当模板和诱导剂，用于吸附矿化的CaP纳米片并将其组装成花状微粒。通过Box-Behnken设计-响应表面方法优化的制备条件达到了3.16 mg / ml的CS，127.22 mg / ml的TPP和89.50 mM的CaCl2。通过扫描电子显微镜（SEM）和透射电子显微镜（TEM）观察系统的形态，结果表明，直径为5-7μm的花状微粒由厚度约40 nm的片状花瓣组成。TEM结果表明，花瓣由厚度为2-5nm的纳米片组成。X射线衍射（XRD）结果表明，CS / CaP微粒的P / Ca比为1.2 / 29/1。体外释放研究表明CS / CaP微粒具有良好的缓释性能和pH敏感释放特性。用Korsmeyer-Peppas模型拟合pH分别为5.8和7.4的药物释放机理。体外细胞活力研究表明，当剂量低于500μg/ ml时，微粒没有明显的细胞毒性。这项工作为新型药物输送系统提供了一个多功能平台，具有出色的pH敏感和缓释性能。