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Inhalation of peptide-loaded nanoparticles improves heart failure
Science Translational Medicine ( IF 15.8 ) Pub Date : 2018-01-17 , DOI: 10.1126/scitranslmed.aan6205
Michele Miragoli 1, 2, 3 , Paola Ceriotti 1, 3 , Michele Iafisco 4 , Marco Vacchiano 1 , Nicolò Salvarani 1, 3 , Alessio Alogna 5, 6 , Pierluigi Carullo 1, 3 , Gloria Belén Ramirez-Rodríguez 4 , Tatiana Patrício 4 , Lorenzo Degli Esposti 4 , Francesca Rossi 7 , Francesca Ravanetti 8 , Silvana Pinelli 2 , Rossella Alinovi 2 , Marco Erreni 1, 9 , Stefano Rossi 2 , Gianluigi Condorelli 1, 3, 9 , Heiner Post 5, 10 , Anna Tampieri 4 , Daniele Catalucci 1, 3
Affiliation  

Peptides are highly selective and efficacious for the treatment of cardiovascular and other diseases. However, it is currently not possible to administer peptides for cardiac-targeting therapy via a noninvasive procedure, thus representing scientific and technological challenges. We demonstrate that inhalation of small (<50 nm in diameter) biocompatible and biodegradable calcium phosphate nanoparticles (CaPs) allows for rapid translocation of CaPs from the pulmonary tree to the bloodstream and to the myocardium, where their cargo is quickly released. Treatment of a rodent model of diabetic cardiomyopathy by inhalation of CaPs loaded with a therapeutic mimetic peptide that we previously demonstrated to improve myocardial contraction resulted in restoration of cardiac function. Translation to a porcine large animal model provides evidence that inhalation of a peptide-loaded CaP formulation is an effective method of targeted administration to the heart. Together, these results demonstrate that inhalation of biocompatible tailored peptide nanocarriers represents a pioneering approach for the pharmacological treatment of heart failure.



中文翻译:

吸入载有肽的纳米颗粒可改善心力衰竭

肽对心血管疾病和其他疾病具有高度选择性和有效作用。然而,目前不可能通过非侵入性方法施用用于心脏靶向治疗的肽,因此代表了科学和技术挑战。我们证明,吸入小的(直径小于50 nm)生物相容性和可生物降解的磷酸钙纳米颗粒(CaPs)可使CaPs从肺树快速转移到血液和心肌,并在其中迅速释放其货物。通过吸入载有治疗性模拟肽的CaP来治疗糖尿病性心肌病的啮齿动物模型,我们先前已证明该肽能改善心肌收缩,从而可恢复心脏功能。转化为猪大动物模型提供了证据,即吸入肽加载的CaP制剂是对心脏进行靶向给药的有效方法。总之,这些结果表明,吸入生物相容性定制肽纳米载体代表了心力衰竭药理学治疗的开创性方法。

更新日期:2018-01-18
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