The use of anti-inflammatory strategies has the potential to be a definitive treatment for
ventricular remodeling post
myocardial infarction (MI). The regulation of macrophage phenotypes by
anti-inflammatory agents contributes to the alleviation of myocardial
fibrosis. However, their poor retention rates severely affect treatment efficacy. Here, we propose a supramolecular compound, NapFFY, to co-assemble with
IL-10 and SN50 as a novel anti-inflammatory SN50/IL-10/NapFFY
hydrogel with cardioprotective properties. Results from the in vitro and in vivo experiments in murine cell line and rats, respectively, demonstrated that the SN50/IL-10/NapFFY
hydrogel exhibits an ideal and sustained release of
IL-10 and SN50. Intramyocardial injection of the SN50/IL-10/NapFFY
hydrogel in a rat model of MI significantly inhibited the expression of proinflammatory
cytokines. It promoted the polarization of M2 macrophages, which reduced cardiomyocyte apoptosis and improved vascularization at the border zones. Specifically, the SN50/IL-10/NapFFY
hydrogel significantly improved heart function and ameliorated
ventricular remodeling 28 days post MI. We envision that the SN50/IL-10/NapFFY
hydrogel could serve as a new
anti-inflammatory agent for the clinical treatment of MI in future studies. STATEMENT OF SIGNIFICANCE: Anti-
inflammation is an ideal strategy for the treatment of
ventricular remodeling post
myocardial infarction (MI). SN50 and
IL-10 have been shown to have diverse roles in antiinflammatory process, respectively. However, direct
intravenous administration or intramyocardial injection of SN50 or
IL-10 is not a viable option given its poor half-life in vivo. This study aimed to evaluate the synergistic cardioprotective effects of a supramolecular
hydrogel loaded with an NF-κB inhibitor (SN50) and
IL-10. Animal experiments showed that the SN50/IL-10/NapFFY
hydrogels ameliorated the inflammatory microenvironment, and improved cardiac function to the
infarct area in a rat model of MI. We anticipate that SN50/IL10NapFFY
hydrogel could be used clinically to treat MI in the near future.