bc6b00397_si_001.pdf (652.41 kB)
Drug Conjugation Affects Pharmacokinetics and Specificity of Kidney-Targeted Peptide Carriers
journal contribution
posted on 2016-09-12, 00:00 authored by Maria Janzer, Gregor Larbig, Armin Kübelbeck, Artjom Wischnjow, Uwe Haberkorn, Walter MierPeptides
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 a multiple-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.