目的优选重组水蛭素-2(rHV2)鼻腔给药纳米粒最佳制备工艺。方法采用壳聚糖与三聚磷酸钠复凝聚法,以包封率、载药量等为评价指标,以单因素考察和正交试验设计,对壳聚糖黏附纳米粒制备过程中有关影响因素及工艺参数进行优化。结果壳聚糖的类型、壳聚糖溶液的pH值、壳聚糖与多聚磷酸钠的最终质量比以及搅拌速率对rHV2纳米粒的包封率和载药量均有较显著影响;优选工艺的包封率可达到70%以上,载药量>8%。结论经优选的工艺稳定可靠,可用于rHV2鼻腔给药纳米粒的制备。 Objective To optimize the preparation of recombinant hirudin-2 (rHV2) nasally administrated nanoparticles. Methods Chitosan and sodium tripolyphosphate complex coagulation method, encapsulation efficiency, drug loading as the evaluation index, single factor study and orthogonal experimental design, chitosan nanoparticles in the process of preparation of the relevant factors And process parameters to optimize. Results The type of chitosan, the pH value of chitosan solution, the final mass ratio of chitosan to sodium polyphosphate and the stirring rate all had significant effects on the entrapment efficiency and drug loading of rHV2 nanoparticles. The encapsulation efficiency can reach more than 70%, drug loading> 8%. Conclusion The optimized process is stable and reliable and can be used for the preparation of rHV2 nasal administration nanoparticles.