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%。目的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 technology of recombinant hirudin-2 (rHV2) nanoparticles for nasal drug delivery. Methods Nanoparticles were prepared using chitosan (CS) and sodium tripolyphosphate (TPP) by complex coacervation. Taking the rHV2 encapsulation efficiency (EE) and drug loading as the evaluation indexes, the influencing factors and technological parameters in the preparation process were investigated by single factor and orthogonal tests. Results The results proved that not only the CS pH value, CS types, and the final proportion of CS to polyphosphate quality, but also the stirring speed in preparation had noticeable effect on the EE and drug loading of rHV2 nanoparticles. The EE and drug loading of optimized formulation could reach over 70% and 8%, repectively. Conclusion The optimized technology is stable and reliable, and could be used for the preparation of rHV2 nasal nanoparticles.

“重大新药创制”科技重大专项(2009ZX09502-008)