TY - JOUR
T1 - Assessment of Squalene-Adenosine Nanoparticles in Two Rodent Models of Cardiac Ischemia-Reperfusion
AU - Brusini, Romain
AU - Tran, Natalie Lan Linh
AU - Cailleau, Catherine
AU - Domergue, Valérie
AU - Nicolas, Valérie
AU - Dormont, Flavio
AU - Calet, Serge
AU - Cajot, Caroline
AU - Jouran, Albin
AU - Lepetre-Mouelhi, Sinda
AU - Laloy, Julie
AU - Couvreur, Patrick
AU - Varna, Mariana
N1 - Publisher Copyright:
© 2023 by the authors.
PY - 2023/7
Y1 - 2023/7
N2 - Reperfusion injuries after a period of cardiac ischemia are known to lead to pathological modifications or even death. Among the different therapeutic options proposed, adenosine, a small molecule with platelet anti-aggregate and anti-inflammatory properties, has shown encouraging results in clinical trials. However, its clinical use is severely limited because of its very short half-life in the bloodstream. To overcome this limitation, we have proposed a strategy to encapsulate adenosine in squalene-based nanoparticles (NPs), a biocompatible and biodegradable lipid. Thus, the aim of this study was to assess, whether squalene-based nanoparticles loaded with adenosine (SQAd NPs) were cardioprotective in a preclinical cardiac ischemia/reperfusion model. Obtained SQAd NPs were characterized in depth and further evaluated in vitro. The NPs were formulated with a size of about 90 nm and remained stable up to 14 days at both 4 °C and room temperature. Moreover, these NPs did not show any signs of toxicity, neither on HL-1, H9c2 cardiac cell lines, nor on human PBMC and, further retained their inhibitory platelet aggregation properties. In a mouse model with experimental cardiac ischemia-reperfusion, treatment with SQAd NPs showed a reduction of the area at risk, as well as of the infarct area, although not statistically significant. However, we noted a significant reduction of apoptotic cells on cardiac tissue from animals treated with the NPs. Further studies would be interesting to understand how and through which mechanisms these nanoparticles act on cardiac cells.
AB - Reperfusion injuries after a period of cardiac ischemia are known to lead to pathological modifications or even death. Among the different therapeutic options proposed, adenosine, a small molecule with platelet anti-aggregate and anti-inflammatory properties, has shown encouraging results in clinical trials. However, its clinical use is severely limited because of its very short half-life in the bloodstream. To overcome this limitation, we have proposed a strategy to encapsulate adenosine in squalene-based nanoparticles (NPs), a biocompatible and biodegradable lipid. Thus, the aim of this study was to assess, whether squalene-based nanoparticles loaded with adenosine (SQAd NPs) were cardioprotective in a preclinical cardiac ischemia/reperfusion model. Obtained SQAd NPs were characterized in depth and further evaluated in vitro. The NPs were formulated with a size of about 90 nm and remained stable up to 14 days at both 4 °C and room temperature. Moreover, these NPs did not show any signs of toxicity, neither on HL-1, H9c2 cardiac cell lines, nor on human PBMC and, further retained their inhibitory platelet aggregation properties. In a mouse model with experimental cardiac ischemia-reperfusion, treatment with SQAd NPs showed a reduction of the area at risk, as well as of the infarct area, although not statistically significant. However, we noted a significant reduction of apoptotic cells on cardiac tissue from animals treated with the NPs. Further studies would be interesting to understand how and through which mechanisms these nanoparticles act on cardiac cells.
KW - cardiac ischemia and reperfusion
KW - drug delivery system
KW - preclinical model
KW - SQAd NPs
UR - http://www.scopus.com/inward/record.url?scp=85166339956&partnerID=8YFLogxK
U2 - 10.3390/pharmaceutics15071790
DO - 10.3390/pharmaceutics15071790
M3 - Article
AN - SCOPUS:85166339956
SN - 1999-4923
VL - 15
JO - Pharmaceutics
JF - Pharmaceutics
IS - 7
M1 - 1790
ER -