Synthesis and Application of Peptides as Drug Carriers

Abstract

An efficient cellular drug delivery is a severe problem due to the charge, the hydrophilic character or the size of many therapeutic agents. High-drug doses, necessary to compensate the reduced bioavailability, often cause strong adverse effects. Synthetic drug delivery vectors will solve this problem, if limitations like low-cellular uptake efficiency or cytotoxicity can be overcome. Among these synthetic vectors, so-called cell-penetrating peptides (CPP) have proven their applicability as drug carriers. The ability to penetrate cellular membranes without the help of any receptor or transporter molecule was also found for derivatives of the native peptide hormone human calcitonin (hCT). We have shown that truncated hCT analogs with a branched peptide design and oligocationic side chain sequences - hCT(18-32)-k 7 and hCT(9-32)-2 br - are very interesting candidates as carrier peptides for drug delivery. Both peptides were found to efficiently shuttle covalently linked small molecules and non-covalently complexed DNA and RNA inside human embryonic kidney cells (HEK 293).