One-week in vivo sustained release of a peptide formulated into in situ forming implants

• Published in: International journal of pharmaceutics 2017-04, Vol.521 (1-2), p.357-360
• Main Authors: Parent, Marianne, Clarot, Igor, Gibot, Sébastien, Derive, Marc, Maincent, Philippe, Leroy, Pierre, Boudier, Ariane
• Format: Article
• Language: English
• Subjects: Animals; Bioavailability; Chemistry, Pharmaceutical; Delayed-Action Preparations; Dimerization; Drug Implants; In situ-forming depot; Life Sciences; LR12; Male; Peptides - administration & dosage; Peptides - chemistry; Pharmaceutical sciences; Pharmacology; Protein Multimerization; Rats; Rats, Wistar; Sustained delivery; TREM-1 inhibitory peptide
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2017.02.046

[Display omitted] 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.