Development of an injectable alginate-collagen hydrogel for cardiac delivery of extracellular vesicles
Keywords: 
Extracellular vesicles
Hydrogel
Myocardial infarction
Alginate
Collagen
Issue Date: 
2022
Project: 
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2017-83734-R/ES/REPARACION CARDIACA UTILIZANDO INGENIERIA TISULAR Y/O EXOSOMAS: MECANISMOS IMPLICADOS Y EFICACIA TERAPEUTICA EN UN MODELO ANIMAL DE INFARTO DE MIOCARDIO
ISSN: 
0378-5173
Note: 
This is an open access article under the CC BY-NC-ND license
Citation: 
Gil-Cabrerizo, P. (Paula); Saludas-Echauri, L. (Laura); Prosper, F. (Felipe); et al. "Development of an injectable alginate-collagen hydrogel for cardiac delivery of extracellular vesicles". International Journal of Pharmaceutics. 629, 2022, 122356
Abstract
Extracellular vesicles (EVs) are nanosized pArtículos with attractive therapeutic potential for cardiac repair. However, low retention and stability after systemic administration limit their clinical translation. As an alternative, the combination of EVs with biomaterial-based hydrogels (HGs) is being investigated to increase their exposure in the myocardium and achieve an optimal therapeutic effect. In this study, we developed and characterized a novel injectable in-situ forming HG based on alginate and collagen as a cardiac delivery vehicle for EVs. Different concentrations of alginate and collagen crosslinked with calcium gluconate were tested. Based on injectability studies, 1% alginate, 0.5 mg/mL collagen and 0.25% calcium gluconate HG was selected as the idoneous combination for cardiac administration using catheter-based systems. Rheological examination revealed that the HG possessed an internal gel structure, weak mechanical properties and low viscosity, facilitating an easy administration. In addition, EVs were successfully incorporated and homogeneously distributed in the HG. After administration in a rat model of myocardial infarction, the HG showed long-term retention in the heart and allowed for a sustained release of EVs for at least 7 days. Thus, the combination of HGs and EVs represents a promising therapeutic strategy for myocardial repair. Besides EVs delivery, the developed HG could represent a useful platform for cardiac delivery of multiple therapeutic agents.

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