纳米碳酸钙负载奥曲肽可吸入缓释制剂研究

采用复分解法制备了3种不同微观形貌的纳米级碳酸钙，研究了添加剂聚丙烯酸（PAA）和聚天冬氨酸钠（PASP）的引入对碳酸钙微观形貌和物相结构的影响；以纳米碳酸钙材料作为药物载体，通过浸渍吸附-冷冻干燥工艺装载药物奥曲肽，构建了可吸入缓释微粉制剂；测试了碳酸钙载体材料的理化性能及体内生物效应，考察了微粉制剂的微观形貌、载药量、体外释药性能、体外吸入沉积性能。结果表明：添加剂的引入可以实现对碳酸钙粒径、微观形貌和物相结构的调控；纳米碳酸钙载体能够有效负载奥曲肽，所制备的微粉制剂保持了载体原有的形貌；在所制备的3种纳米碳酸钙载体材料中，由球形与棒形混杂状纳米碳酸钙载体制备的微粉制剂的综合性能最佳，其载药量为31.3%，有效部位沉积率达到42%，持续释药时间达到48 h，具有较好的体外吸入沉积性能和体外释药性能；球形与棒形混杂状纳米碳酸钙对THP-1细胞无毒性，低浓度时不会引起炎症效应，并且可以将药物有效地递送至肺部并在肺部滞留7 d，具有作为可吸入缓释制剂载体的潜力。

Inhalable sustained-release preparations of nano-calcium carbonate loaded with octreotide

Three types of nano-calcium carbonate with different micromorphologies have been prepared by metathesis methods. The effects of adding polyacrylic acid (PAA) and sodium of polyaspartic acid (PASP) on the micromorphology and phase structure of the calcium carbonate were studied. Using the nano-calcium carbonate as a drug carrier, the drug octreotide was loaded by an impregnation adsorption-freeze-drying process to afford an inhalable sustained-release micro-powder preparation. The physicochemical properties and in vivo biological effects of the calcium carbonate carrier materials were tested. The micromorphology, drug loading, in vitro release performance and in vitro inhalation deposition performance of the micro-powder preparations were studied. The results show that the addition of additives can control the particle size, microstructure and phase structure of the calcium carbonate. Octreotide can be effectively loaded on the nano-calcium carbonate carrier, and the resulting powder maintains the original morphology of the carrier. Of the three types of nano-calcium carbonate carrier materials prepared, the micro-powder prepared using a mixture of spherical and rod-shaped nano-calcium carbonate carrier particles had the best overall performance:its drug loading was 31.3%, the effective site deposition rate reached 42%, and the continuous release time was 48 h, with good in vitro inhalation deposition performance and in vitro drug release performance. The mixed spherical and rod-shaped nano-calcium carbonate had no toxicity to THP-1 cells, did not cause any inflammatory effects at low concentrations, and can effectively deliver the drug to the lungs and be retained in the lungs for seven days, showing that it is a potential carrier for practical inhalable sustained-release preparations.