Drug conjugation affects pharmacokinetics and specificity of kidney-targeted peptide carriers

• Verfasst von: Janzer, Maria [VerfasserIn]
• Verfasst von: Wischnjow, Artjom [VerfasserIn]
• Verfasst von: Haberkorn, Uwe [VerfasserIn]
• Verfasst von: Mier, Walter [VerfasserIn]
• Titel: Drug conjugation affects pharmacokinetics and specificity of kidney-targeted peptide carriers
• Verf.angabe: Maria Janzer, Gregor Larbig, Armin Kübelbeck, Artjom Wischnjow, Uwe Haberkorn, Walter Mier
• Umfang: 9 S.
• Fussnoten: Gesehen am 29.11.2017
• Titel Quelle: Enthalten in: Bioconjugate chemistry
• Jahr Quelle: 2016
• Band/Heft Quelle: 27(2016), 10, S. 2441-2449
• ISSN Quelle: 1520-4812
• DOI: doi:10.1021/acs.bioconjchem.6b00397
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1565843940

Abstract

Peptides play a crucial role as biological vectors for targeted drug delivery. In particular, in cases of specific receptor expression, peptides are highly potent carriers for drug targeting approaches. Kidney-targeted peptides require specific attention because of the necessity of fine-tuning their behavior with respect to extraction and retention in the complex architecture of the kidneys. To enable optimal carrier capacity and targeting specificity, this study focuses on pharmacokinetic profiles of different kidney-specific peptides and examines the impact of drug conjugation. γ-Scintigraphy was used to compare the pharmacokinetics and specificity prior to and after drug conjugation of the model drug α-lipoic acid. The results revealed that drug conjugation dramatically affects the targeting specificity, in the worst case leading to a total loss of kidney specificity. Nevertheless, efficient drug transport was achieved with the novel kidney carrier (KKEEE)3K, even with amultiple-drug loading of α-lipoic acid after intraveous and intraperitoneal administration. In contrast to other peptidic molecules, (KKEEE)3K demonstrated its significant potential as a promising carrier candidate for kidney-targeted drug delivery to proximal tubule cells, especially for the treatment of severe kidney diseases.