Development and in vivo characterization of a novel peptide drug delivery system providing extended plasma half life.
作者： Gul Shahnaz , Javed Iqbal , Deni Rahmat , Glen Perera , Flavia Laffleur
DOI: 10.1016/J.JCONREL.2011.09.092
关键词: Half-life 、 Pharmacology 、 Biological half-life 、 Conjugate 、 Stereochemistry 、 In vivo 、 Glutathione 、 Thiol 、 Peptide 、 Chemistry 、 Pharmacokinetics
摘要: Abstract It was the aim of this study to develop a sustained parenteral peptide (DALCE) delivery system by immobilization DALCE thiolated carboxymethyl dextran-cysteine (CMD-Cys) via disulfide bond formation. The resulting CMD-Cys–DALCE conjugate displayed 22.6 ± 7.9% (m/m) (mean ± S.D.; n = 3). conjugation with CMD-Cys confirmed FTIR-ATR spectroscopy. In vitro release studies in presence 2 μM/ml reduced glutathione (GSH) being also available plasma showed over time period 8 h, because thiol/disulfide exchange reactions. For vivo pharmacokinetic study, and were administered intravenously male Sprague–Dawley rats at dose 1 mg/kg. AUC 0-8 (ng.min/ml) determined be 268848 ± 924 40019 ± 495 for DALCE, respectively. mean residence (MRT) 256 ± 8 53.1 ± 9.5 min more than 5-fold increased elimination half-life ( p
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