聚合物微气泡的优化及其体内外超声成像研究

Optimized polymer microbubbles for ultrasound imaging in vitro/vivo

目的 :对以左旋聚乳酸(poly L-lactic acid,PLLA)及聚乙烯醇(polyvinyl alcohol,PVA)为膜材的微气泡,在稳定性和粒径两个方面进行了优化,使其在保持超声成像增强能力的同时,更适于体内应用。方法:首先对PVA进行了羧基化修饰,使制备的微气泡表面含有羧基,Zeta电位达到-38.87±2.19 m V,从而由于静电斥力提高了微气泡的稳定性。其次,通过调节制备过程中的PVA浓度、水相油相比、乳化速度3种因素,实现了对微气泡粒径的控制。结果:对优化后平均粒径为1.38μm、粒径分布均匀、性质稳定的微气泡进行了体内外超声成像实验,证实其在体外能够显著增强超声成像效果,在体内既可以通过瘤内注射迅速提高肿瘤部位超声显影质量,又可以通过静脉注射,经血液循环到达肿瘤部位,在一段时间的累积之后,增强超声成像效果。结论:本研究为微气泡的体内应用打下了良好基础。

Objective：This study focuses on the optimization on stability and size of MBs with poly-L-lactic acid（poly L-lactic acid,PLLA）and polyvinyl alcohol（polyvinyl alcohol,PVA）as shell materials,which made MBs more suitable to work in vivo at the same time keeping the ability of enhancing the ultrasound imaging. Methods：First,PVA was modified to obtain telechelic PVA with carboxylic groups at the chain ends. The modified PVA was used to fabricate MBs present carboxyl on their surface,whose Zeta potential was-38.87 ± 2.19 m V,thus improving the stability of MBs. Next,The particle size and stability of MBs were regulated through adjustments the three factors,i.e. the concentration of PVA aqueous solution,the water-oil ratio of the first emulsification and the rate of second emulsification during the preparation process. Results：In vitro / vivo US imaging experiment was performed on the optimized MBs,which had a average particle size of 1.38 μm,uniform particle size distribution and good stability. In vitro experiments showed that the MBs exhibited significantly ultrasound（US）contrast enhancement. In vivo US imaging of tumors in nude mice showed that,by intratumoral injection,MBs can rapidly improve the ultrasound imaging of tumor;by intravenous injection,MBs can reach the tumor site through the blood circulation,accumulate in the tumor site after a period of time,and enhance ultrasound imaging.Conclusion：This study lays a good foundation for the application of MBs in vivo.