Drug delivery of oligonucleotides by peptides.
Oligonucleotides are promising tools for in vitro studies where specific downregulation of proteins is required. In addition, antisense oligonucleotides have been studied in vivo and have entered clinical trials as new chemical entities with various therapeutic targets such as antiviral drugs or for tumour treatments. The formulation of these substances were widely studied in the past. With this review we will focus on peptides used as drug delivery vehicles for oligonucleotides. Different strategies are summarised. Cationically charged peptides from different origins were used e.g. as cellular penetration enhancers or nuclear localisation tool. Examples are given for Poly-L-lysine alone or in combination with receptor specific targeting ligands such as asialoglycoprotein, galactose, growth factors or transferrin. Another large group of peptides are those with membrane translocating properties. Fusogenic peptides rich in lysine or arginine are reviewed. They have been used for DNA complexation and condensation to form transport vehicles. Some of them, additionally, have so called nuclear localisation properties. Here, DNA sequences, which facilitate intracellular trafficking of macromolecules to the nucleus were explored. Summarizing the present literature, peptides are interesting pharmaceutical excipients and it seems to be feasible to combine the specific properties of peptides to improve drug delivery devices for oligonucleotides in the future.
Institute for Pharmaceutical Technology, Johann Wolfgang Goethe-University, Frankfurtam Main, Germany.
Dirk
D
Lochmann
Edith
E
Jauk
Andreas
A
Zimmer
D000818:Animals; D001692:Biological Transport; D002462:Cell Membrane / Q000378:metabolism; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D005079:Excipients / Q000737:chemistry*; D006801:Humans; D009841:Oligonucleotides / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D010455:Peptides / Q000737:chemistry*
D004337:Drug Carriers; D005079:Excipients; D009841:Oligonucleotides; D010455:Peptides