摘要
目的制备一种使用新型稳定剂的紫杉醇(PTX)纳米混悬剂。方法以新型聚合物聚(L-丙氨酸)-b-聚(L-天冬氨酸)为稳定剂,采用微沉淀-高压匀质法制备紫杉醇纳米悬浮剂,并对其制剂学性质进行考察。结果动态光散射法测定结果显示,PTX纳米混悬剂的粒径和Zeta电位分别为(189.5±3.7)nm和(-31.2±0.3)m V。透射电镜表明PTX纳米悬浮剂为棒状晶体。PTX纳米混悬剂的溶出度与粗晶体相比显著增加,且类似于PTX注射剂。储存稳定性、稀释稳定性和血浆稳定性实验均表明,相比于其他传统的表面活性剂和聚合物,以聚(L-丙氨酸)-b-聚(L-天冬氨酸)为稳定剂制备的PTX纳米混悬剂更加稳定。结论聚(L-丙氨酸)-b-聚(L-天冬氨酸)作为纳米混悬剂的稳定剂,能提供静电斥力和空间位阻作用,对PTX纳米粒具有较好的稳定作用,这使得该聚合物有望成为PTX和其他难溶性药物纳米混悬剂的新型稳定剂。
Objection To prepare a paclitaxel nanosuspension(PTX-Nanos)using a novel stabilizer. Methods A PTX-poly(amino acid)-nanosuspension(PTX-PAA-Nanos)was prepared using the poly(L-alanine)-b-poly(L-aspartic acid)as stabilizer,by a microprecipitation-high pressure homogenization method,and the pharmaceutical properties were investigated. Results Particle size and Zeta potential of the PTX-PAA-Nanos were(189.5±3.7)nm and(-31.2±0.3)mV,respectively,as determined by dynamic light scattering method. Transmission electronmicroscopy(TEM)revealed that the morphology of PTX-PAA-Nanos was of rod-like crystals.The dissolution rate of PTX-PAA-Nanos was significantly increased compared with the crude PTX crystals and was similar to that of PTX injection. The tests of storage stability,dilution stability and plasma stability all showed that PTX-PAA-Nanos was significantly more stable than PTX-Nanos stabilized with other traditional surfactants and polymers. Conclusion With the properties of electrostatic repulsion and space steric hindrance,the poly(L-alanine)-b-poly(L-aspartic acid),a novel nanomaterial,has a good stabilizing effect for PTX and a great potential as an alternative stabilizer for nanosuspensions of PTX and other poorly water-soluble drugs.
出处
《国际药学研究杂志》
CAS
CSCD
北大核心
2018年第5期393-399,共7页
Journal of International Pharmaceutical Research
基金
河南省科技攻关项目(182102310811)
河南省高等教育教学改革研究与实践重点项目(2017SJGLX177)
