title: One-week in vivo sustained release of a peptide formulated into in situ forming implants.
abstract: The LR12 peptide has been reported to reduce the size of infarct and improve both cardiac function and survival in myocardial infarction in murine models, after daily repeated intraperitoneal injections. In order to protect peptide from degrading and to prolong its release, in situ implants based on biocompatible biodegradable polymers were prepared and both in vitro and in vivo releases were evaluated after subcutaneous administration to Wistar rats. A progressive and complete release was obtained in vitro in 3 weeks. In vivo, a 7-day sustained release was demonstrated after administrating the formulation once; bioavailability was improved by protecting the peptide against the degradation identified as a dimerization through disulfide bond formation. As a conclusion, in situ forming formulations are a suitable alternative for the therapeutic use of this peptide.
authors.affiliation: Université de Lorraine, CITHEFOR, EA 3452, Nancy, France. Electronic address: marianne.parent@univ-lorraine.fr.
authors.forename: Marianne
authors.initials: M
authors.lastname: Parent
authors.affiliation: Université de Lorraine, CITHEFOR, EA 3452, Nancy, France.
authors.forename: Igor
authors.initials: I
authors.lastname: Clarot
authors.affiliation: Université de Lorraine, INSERM U1116, Vandœuvre-lès-Nancy, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Gibot
authors.affiliation: INOTREM, Vandœuvre-lès-Nancy, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Derive
authors.affiliation: Université de Lorraine, CITHEFOR, EA 3452, Nancy, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Maincent
authors.affiliation: Université de Lorraine, CITHEFOR, EA 3452, Nancy, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Leroy
authors.affiliation: Université de Lorraine, CITHEFOR, EA 3452, Nancy, France.
authors.forename: Ariane
authors.initials: A
authors.lastname: Boudier
mesh_terms: D000818:Animals; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D004343:Drug Implants; D008297:Male; D010455:Peptides / Q000008:administration & dosage* / Q000737:chemistry; D055503:Protein Multimerization; D051381:Rats; D017208:Rats, Wistar
chemical_list: D003692:Delayed-Action Preparations; D004343:Drug Implants; D010455:Peptides
keywords: Bioavailability; Dimerization; In situ-forming depot; LR12; Sustained delivery; TREM-1 inhibitory peptide