Pharmacology active microcarriers delivering HGF associated with extracellular vesicles for myocardial repair


Posted: 2021-11-08 20:00:00
Eur J Pharm Biopharm . 2021 Nov 5;S0939-6411(21)00273-3. doi: 10.1016/j.ejpb.2021.10.018. Online ahead of print. Affiliations Expand Affiliations 1 SOPAM, U1063, INSERM, UNIV Angers, SFR ICAT, Angers, France; CRCINA, UMR 1232, INSERM, Université de Nantes, Université d'Angers, F-49933 Angers, France. 2 UNIV Angers, SFR ICAT4208, Angers, France. 3 CRCINA, UMR 1232, INSERM, Université de Nantes, Université d'Angers, F-49933 Angers, France. 4 SOPAM, U1063, INSERM, UNIV Angers, SFR ICAT, Angers, France. 5 CRCINA, UMR 1232, INSERM, Université de Nantes, Université d'Angers, F-49933 Angers, France. Electronic address: claudia.montero-menei@univ-angers.fr. 6 SOPAM, U1063, INSERM, UNIV Angers, SFR ICAT, Angers, France. Electronic address: carmen.martinez@inserm.fr. Item in Clipboard Melody Riaud et al. Eur J Pharm Biopharm. 2021. Show details Display options Display options Format Eur J Pharm Biopharm . 2021 Nov 5;S0939-6411(21)00273-3. doi: 10.1016/j.ejpb.2021.10.018. Online ahead of print. Affiliations 1 SOPAM, U1063, INSERM, UNIV Angers, SFR ICAT, Angers, France; CRCINA, UMR 1232, INSERM, Université de Nantes, Université d'Angers, F-49933 Angers, France. 2 UNIV Angers, SFR ICAT4208, Angers, France. 3 CRCINA, UMR 1232, INSERM, Université de Nantes, Université d'Angers, F-49933 Angers, France. 4 SOPAM, U1063, INSERM, UNIV Angers, SFR ICAT, Angers, France. 5 CRCINA, UMR 1232, INSERM, Université de Nantes, Université d'Angers, F-49933 Angers, France. Electronic address: claudia.montero-menei@univ-angers.fr. 6 SOPAM, U1063, INSERM, UNIV Angers, SFR ICAT, Angers, France. Electronic address: carmen.martinez@inserm.fr. Item in Clipboard CiteDisplay options Display options Format Abstract Despite the curative approaches developed against myocardial infarction, cardiac cell death causes dysfunctional heart contractions that depend on the extent of the ischemic area and the reperfusion period. Cardiac regeneration may allow neovascularization and limit the ventricular remodeling caused by the scar tissue. We have previously found that large extracellular vesicles, carrying Sonic Hedgehog (lEVs), displayed proangiogenic and antioxidant properties, and decreased myocardial infarction size when administrated by intravenous injection. We propose to associate lEVs with pharmacology active microcarriers (PAMs) to obtain a combined cardioprotective and regenerative action when administrated by intracardiac injection. PAMs made of poly-D,L-lactic-coglycolic acid-poloxamer 188-poly-D,L-lactic-coglycolic acid and covered by fibronectin/poly-D-lysine provided a biodegradable and biocompatible 3D biomimetic support for the lEVs. When compared with lEVs alone, lEVs-PAMs constructs possessed an enhanced in vitro pro-angiogenic ability. PAMs were designed to continuously release encapsulated hepatocyte growth factor (PAMsHGF) and thus, locally increase the activity of the lEVs by the combined anti-fibrotic properties and regenerative properties. Intracardiac administration of either lEVs alone or lEVs-PAMsHGF improved cardiac function in a similar manner, in a rat model of ischemia-reperfusion. Moreover, lEVs alone or the IEVs-PAMsHGF induced arteriogenesis, but only the latter reduced tissue fibrosis. Taken together, these results highlight a promising approach for lEVs-PAMsHGF in regenerative medicine for myocardial infarction. Keywords: HGF; extracellular vesicles; microcarriers; myocardial repair. Copyright © 2021 Elsevier B.V. All rights reserved. Conflict of interest statement Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. [x] Cite Copy Format: Send To [x]

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