Baghbani Fatemeh, Moztarzadeh Fathollah, Mohandesi Jamshid Aghazadeh, Yazdian Fatemeh, Mokhtari-Dizaji Manijhe
Biomaterials Group, Faculty of Biomedical Engineering (Center of Excellence), Amirkabir University of Technology, Tehran, Iran.
Biomaterials Group, Faculty of Biomedical Engineering (Center of Excellence), Amirkabir University of Technology, Tehran, Iran.
Int J Biol Macromol. 2016 Dec;93(Pt A):512-519. doi: 10.1016/j.ijbiomac.2016.09.008. Epub 2016 Sep 4.
Perfluorocarbon nanoemulsions are a new class of multifunctional stimuli-responsive nanocarriers which combine the properties of passive-targeted drug carriers, ultrasound imaging contrast agents, and ultrasound-responsive drug delivery systems. Doxorubicin-loaded alginate stabilized perflourohexane (PFH) nanodroplets were synthesized via nanoemulsion preparation method and their ultrasound responsivity, imaging, and therapeutic properties were studied. Doxorubicin was loaded into the nanodroplets (39.2nm) with encapsulation efficiency of 92.2%. In vitro release profile of doxorubicin from nanodroplets was an apparently biphasic release process and 12.6% of drug released from nanodroplets after 24h incubation in PBS, pH=7.4. Sonication with 28kHz therapeutic ultrasound for 10min triggered droplet-to-bubble transition in PFH nanodroplets which resulted in the release of 85.95% of doxorubicin from nanodroplets. Microbubbles formed by acoustic vaporization of the nanodroplets underwent inertial cavitation. In the breast cancer mice models, ultrasound-mediated therapy with doxorubicin-loaded PFH nanodroplets showed excellent anti-cancer effects characterized by tumor regression. Complete tumor regression was observed for the group in which doxorubicin-loaded nanodroplets were combined with ultrasound, whereas the tumor growth inhibition of doxorubicin -loaded nanodroplets was 89.6%. These multifunctional nanodroplets, with excellent therapeutic and ultrasound properties, could be promising drug delivery systems for chemotherapeutic application.
全氟碳纳米乳剂是一类新型的多功能刺激响应性纳米载体，它结合了被动靶向药物载体、超声成像造影剂和超声响应性药物递送系统的特性。通过纳米乳剂制备方法合成了负载阿霉素的海藻酸盐稳定全氟己烷（PFH）纳米液滴，并对其超声响应性、成像和治疗特性进行了研究。阿霉素被载入纳米液滴（39.2nm）中，包封率为92.2%。阿霉素从纳米液滴的体外释放曲线是一个明显的双相释放过程，在pH = 7.4的PBS中孵育24小时后，有12.6%的药物从纳米液滴中释放出来。用28kHz治疗性超声超声处理10分钟引发了PFH纳米液滴中的液滴到气泡的转变，这导致85.95%的阿霉素从纳米液滴中释放出来。纳米液滴声致汽化形成的微泡发生了惯性空化。在乳腺癌小鼠模型中，用负载阿霉素的PFH纳米液滴进行超声介导的治疗显示出以肿瘤消退为特征的优异抗癌效果。对于负载阿霉素的纳米液滴与超声联合使用的组，观察到肿瘤完全消退，而负载阿霉素的纳米液滴对肿瘤生长的抑制率为89.6%。这些具有优异治疗和超声特性的多功能纳米液滴有望成为化疗应用的药物递送系统。
