Pharmacokinetics Rational Design of CPP-based Drug Delivery Systems: Considerations from

ISSN: 1873-4316 (Online)
ISSN: 1389-2010 (Print)


Volume 15, 12 Issues, 2014


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Current Pharmaceutical Biotechnology

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Editor-in-Chief:
Zeno Foldes-Papp
Visiting Professor of Medical Biochemistry
HELIOS Clinical Center of Emergency Medicine
Department for Internal Medicine
Alte-Koelner-Strasse 9
D-51688 Koeln-Wipperfuerth
Germany


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Pharmacokinetics Rational Design of CPP-based Drug Delivery Systems: Considerations from

Author(s): Arite Mickan, Dikran Sarko, Uwe Haberkorn and Walter Mier

Affiliation: Department of Nuclear Medicine, University Hospital Heidelberg, INF 400, 69120 Heidelberg, Germany

Abstract

Therapeutics are restricted from cellular internalization due to the biological barrier formed by the cell membrane. Especially for therapeutics with high molecular weight, strategies are required to enable delivery to intracellular targets. Cell-penetrating peptides (CPPs) represent a powerful tool to mediate the entry of large cargos such as proteins, siRNA and nanoparticles. The high diversity of CPPs is the prerequisite to use this class of carriers for various applications. However, therapies based on CPPs are hampered by their unfavorable pharmacokinetics, mainly dominated by their rapid renal clearance and their lack of specificity. Rational design is required to overcome these disadvantages and thereby exploits the actual potential of CPPs. We summarize and highlight the current state of knowledge with special emphasis on pharmacokinetics. The unclear internalization pathways of CPPs remain one of the main obstacles and therefore have been in the focus of research. In this review, several promising strategies such as the combination with targeting sequences, activatable CPPs and adjustment of the molecular weight are described. In addition, new absorption pathways such as nasal, pulmonary or transdermal uptake expand the applicability of CPPs and may be a promising prospect for clinical application


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Article Details

Volume: 15
First Page: 1
Page Count: 1
DOI: 10.2174/1389201015666140813125503
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