Intratumoral Distribution of YSNSG Cyclopeptide in a Mouse Melanoma Model using Microdialysis.
Fiche publication
Date publication
décembre 2019
Journal
European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences
Auteurs
Membres identifiés du Cancéropôle Est :
Dr BRASSART-PASCO Sylvie
Tous les auteurs :
Slimano F, Djerada Z, Guerin J, Bellouch MI, Brassart-Pasco S, Dukic S
Lien Pubmed
Résumé
The YSNSG peptide is a synthetic cyclopeptide targeting αβ integrin with antitumor activity. Previous study has determined main pharmacokinetic parameters in plasma and in tissue in healthy animals using microdialysis. First we aim to assess the impact of a 20 mg/kg dosage instead of 10 mg/kg in tumor growth inhibition. Secondly we aim to investigate the YSNSG peptide distribution in two different tumor regions in animals with melanoma. C57BL/6 mice were exposed at Days 8, 10 and 12 after melanoma cells implantation (B16F1) to different dosage of YSNSG peptide or control, respectively (n=10 per group). Data analysis was performed at D16, 20 and 24 with a Nonlinear Mixed-Effects (NLME) approach. For pharmacokinetic study n=8 mice (same disease condition) received YSNSG peptide by intravenous after insertion of two microdialysis probes in central peripheral region of tumor, respectively. Plasma and tissue samples were collected during 2 hours. A non-compartmental analysis was performed to determine main pharmacokinetic parameters. There was a significant tumor growth inhibition in mice receiving 20 mg/kg vs Control (p<0.02). Main plasma parameters were half-life elimination 25.8 ± 8.2 min, volume of distribution 11.9 ± 0.4 mL, clearance 19.8 ± 9.4 mL/h and area under the curve 1,173.6 µg.min/mL. Penetration rate of the YSNSG peptide from plasma to tumor tissue were 3.3 ± 2.1% and 3.4 ± 2.7% in central and peripheral, respectively. Contrary to subcutaneous distribution in healthy animals the distribution of the YSNSG peptide into tumoral tissue is low but seems non-heterogeneous between central and peripheral tumor region.
Mots clés
Integrin antagonist, YSNSG, cyclopeptide, intratumoral distribution, melanoma, microdialysis, pharmacokinetic
Référence
Eur J Pharm Sci. 2019 Dec 19;:105201