Preparation of dual-targeted pH-sensitive DOX prodrug-microbubble complex and drug release experiment in vitro
10.3760/cma.j.issn.1004-4477.2018.04.019
- VernacularTitle:双配体pH敏感阿霉素前药-微泡复合物制备及体外药物释放研究
- Author:
Li ZHANG
1
;
Wanxian LUO
;
Li YANG
;
Shuyi LUO
;
Shiyu ZHANG
;
Yu LIANG
;
Yingjia LI
Author Information
1. 南方医科大学南方医院超声医学科
- Keywords:
Sonication;
Doxorubicin;
Microbubbles;
Targeted therapy
- From:
Chinese Journal of Ultrasonography
2018;27(4):348-352
- CountryChina
- Language:Chinese
-
Abstract:
Objective To prepare dual-targeted pH-sensitive DOX prodrug-microbubble complex and explore the characterization of complex with ultrasound as well as drug release in vitro . Methods Dual-targeted ligands ,cRGD and folate were conjugated with heparin using carbodiimide method ,and then the dual-targeted pH-sensitive DOX prodrug was synthesized by coupling DOX via a pH-sensitive hydrazone bond . The prodrug was combined with microbubbles to prepare complex by biotin-avidin system . The characterization of complex with/without ultrasound was investigated for size ,morphology and drug loaded capacity .In vitro drug release manner of complex with/without at different pH was analyzed . Results DOX content of the prodrug determined by UV Spectrophotometry was about 18 .9％ . Dynamic laser light scattering analysis( DLS) ,corresponding to transmission electron microscope( TEM ) findings ,revealed its inhomogeneous size distribution [ mean size ( 159 .7 ± 24 .5) nm and ( 1089 .0 ± 174 .9) nm ] . However ,the complex was dispersed into uniform fragment after ultrasound irradiation [ mean size ( 155 .9 ± 29 .8) nm , polymer dispersity index( PDI) 0 .22 ,Zeta potential - ( 20 .6 ± 3 .4) mV ] . The cumulative release rate of DOX from both complex and complex with ultrasound at pH 5 .0 were much faster than that at pH 7 .4 , displaying a pH-triggered release manner . Conclusions Dual-targeted pH-sensitive DOX prodrug-microbubble complex displays excellent drug release activity in acid environment . Uniform fragment and smaller particle size of complex could be achieved via ultrasound irradiation ,promoting DOX accumulation within tumor tissue and facilitating in vivo antitumor ability .
