title: RGD(F/S/V)-Dex: towards the development of novel, effective, and safe glucocorticoids.
abstract: Dexamethasone (Dex) is an effective glucocorticoid in treating inflammation and preventing rejection reaction. However, the side effects limit its clinical application. To improve its druggable profile, the conjugates of RGD-peptide-modified Dex were presented and their enhanced anti-inflammation activity, minimized osteoporotic action, and nanoscaled assembly were explored. (RGD stands for Arg-Gly-Asp. Standard single letter biochemical abbreviations for amino acids have been used throughout this paper.) In respect of the rejection reaction, the survival time of the implanted myocardium of the mice treated with 1.43 µmol/kg/d of the conjugates for 15 consecutive days was significantly longer than that of the mice treated with 2.5 µmol/kg/d of Dex, and the conjugates, but not Dex, exhibited no toxic action. At a single dose of 14.3 µmol/kg (100 times minimal effective dose, 0.143 µmol/kg), the conjugates induced no liver, kidney, or systemic toxicity. At the dose of 1.43 µmol/kg, the conjugates, but not Dex, prolonged the bleeding time of the mice, and inhibited the thrombosis of the rats. In water and rat plasma, the conjugates formed nanoparticles of 14-250 and 101-166 nm in diameter, respectively. Since the nanoparticles of ~100 nm in size cannot be entrapped by macrophages in the circulation, RGDF-Dex would particularly be worthy of development, since its nanoparticle diameter is 101 nm.
authors.affiliation: Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Beijing Laboratory of Biomedical Materials, College of Pharmaceutical Sciences, Capital Medical University, Beijing, People's Republic of China.
authors.forename: Xueyun
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Beijing Laboratory of Biomedical Materials, College of Pharmaceutical Sciences, Capital Medical University, Beijing, People's Republic of China; Faculty of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Beijing Laboratory of Biomedical Materials, College of Pharmaceutical Sciences, Capital Medical University, Beijing, People's Republic of China.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Beijing Laboratory of Biomedical Materials, College of Pharmaceutical Sciences, Capital Medical University, Beijing, People's Republic of China.
authors.forename: Haimei
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Beijing Laboratory of Biomedical Materials, College of Pharmaceutical Sciences, Capital Medical University, Beijing, People's Republic of China.
authors.forename: Shurui
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Beijing Laboratory of Biomedical Materials, College of Pharmaceutical Sciences, Capital Medical University, Beijing, People's Republic of China.
authors.forename: Jianhui
authors.initials: J
authors.lastname: Wu
authors.affiliation: Guangxi Pusen Biotechnology Co. Ltd., Nanning, Guangxi, People's Republic of China.
authors.forename: Yuanbo
authors.initials: Y
authors.lastname: Song
authors.affiliation: Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Beijing Laboratory of Biomedical Materials, College of Pharmaceutical Sciences, Capital Medical University, Beijing, People's Republic of China.
authors.forename: Shiqi
authors.initials: S
authors.lastname: Peng
mesh_terms: D000818:Animals; D003907:Dexamethasone / Q000009:adverse effects / Q000737:chemistry* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005938:Glucocorticoids / Q000009:adverse effects / Q000737:chemistry* / Q000494:pharmacology*; D007249:Inflammation / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008813:Mice, Inbred ICR; D008968:Molecular Conformation; D053758:Nanoparticles / Q000737:chemistry; D009842:Oligopeptides / Q000737:chemistry*; D010316:Particle Size; D051381:Rats; D017208:Rats, Wistar; D013499:Surface Properties
chemical_list: D005938:Glucocorticoids; D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid; D003907:Dexamethasone
keywords: Dexamethasone; acute toxicity; coagulation; development; immunosuppression; nanomedicine; thrombus