期刊
JOURNAL OF CONTROLLED RELEASE
卷 308, 期 -, 页码 162-171出版社
ELSEVIER
DOI: 10.1016/j.jconrel.2019.07.017
关键词
Capsules; Ultrasound; Drug delivery; Thrombolysis; Layer-by-layer; Nanomedicine
资金
- Spanish MINECO-AEI/FEDER [SAF2017-84267-R, MAT2016-80266-R, MAT2015-74381-JIN, CTQ2017-89588-R]
- Xunta de Galicia (Centro singular de investigacion de Galicia acreditacion 2016-2019) [ED431G/09]
- European Union (European Regional Development Fund - ERDF) [732678, 686009]
- Miguel Servet Program of Instituto de Salud Carlos III [CP14/00154, CPII17/00027]
- RyC program [RyC-2014-16962, RyC-2017-23457]
- 2017 Leonardo Grant for Researchers and Cultural Creators BBVA Foundation
- JdC program [IJCI-2016-30706]
- Xunta de Galicia fellowship PhD program [IN606A-2018/031]
- CONACYT PhD fellowship program
External stimuli such as light, magnetic fields or ultrasounds allow for controlled drug release from nanocarriers with spatiotemporal resolution. Such tetherless approaches may become a straightforward solution to overcome the specificity problems typically associated with nanomedicines. Most of current nanomedicines suffer of very low specificity in vivo, thus rendering efficient targeted delivery among the most wanted breakthroughs in the fields of nanotechnology and medicine. Here we present a sonosensitive, sub-micrometric layer-by-layer capsule system for ultrasound-controlled delivery of macromolecules in vivo. As a proof of concept, the serine protease recombinant tissue plasminogen activator (rtPA), a thrombolytic drug widely employed for the treatment of acute ischemic stroke and other thromboembolic pathologies, is used as encapsulated active compound. The activity of encapsulated rtPA and its ultrasound-induced delivery from the cavity of the capsules are demonstrated. We show, first, that rtPA encapsulation prevents its endogenous biological inactivation and do not interfere with the thrombolytic activity of the drug. Second, upon ultrasound application, delivery of rtPA promotes breakdown of blood clots in vitro. Finally, the ultrasound-triggered in vivo delivery of rtPA from capsules intravenously administrated in mice is demonstrated.
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