穿膜肽修饰的PHBHHx负载紫杉醇递药系统构建

Preparation of PHBHHx Loaded Paclitaxel Nanoparticles Modified by Membrane Penetrating Peptide

采用乳化溶剂挥发法、基因重组和蛋白纯化技术,制备了穿膜肽修饰的3-羟基丁酸-3-羟基己酸共聚酯(PHBHHx)负载紫杉醇(PTX)递药系统。通过调控乳化剂的种类、用量、包封材料与药物比例优化了纳米微球的尺寸、药物包封率及载药量,并对递药系统的尺寸、形貌进行了表征。结果表明:水包油型乳化剂选用0.5 mL的吐温-20、水相乳化剂选用60 mL(1%)聚乙烯醇,微球尺寸达到150 nm左右时,均匀性良好;PTX与PHBHHx比例为1∶50时,药物包封率及载药量达到最优,分别为81.02%和50.9 mg/g;递药系统分散度好,表面略显粗糙,基本呈球形,粒径约为150 nm。在最优条件下制备的PTX载药系统粒径较小,包封率较高,易实现功能化蛋白修饰,为PTX纳米药物提供了一种新的设计思路。

The membrane penetrating peptide modified 3-hydroxybutyrate-co-3-hydroxyhexanoate(PHBHHx)loaded paclitaxel(PTX)delivery system was prepared by emulsion solvent evaporation,gene recombination and protein purification.The size of nanospheres,drug encapsulation efficiency,and drug loading were optimized by changing the experimental parameters.The size and morphology of the drug delivery system were then characterized.The results show that when 0.5 mL of Tween-20 is selected as the oil in water emulsifier and 60 mL(1%)of PVA is selected as the aqueous phase emulsifier,the size of the nanospheres reaches 150 nm and the dispersibility is good.The encapsulation efficiency reaches 81.02%,and the drug loading is 50.9 mg/g when the ratio of paclitaxel to PHBHHx is 1∶50.The drug delivery system has good dispersion,slightly rough surface,spherical shape,and particle size is about 150 nm.The PTX drug loading system prepared under the optimal conditions has small particle size,high encapsulation efficiency and is easy to realize functional protein modification,which provides a new design idea for PTX nanodrug.