APPLICATION OF MEMBRANE-ACTIVE PEPTIDES FOR DRUG AND GENE DELIVERY ACROSS CELLULAR MEMBRANES

Naturally occurring peptides and protein domains with amphipathic sequ ences play a dominant role in physiological, lipid membrane-reorganizi ng processes Like fusion, disruption, or pore formation. More recently this capacity to modulate membrane integrity has been exploited for d rug delivery into cells. Incorporation of synthetic membrane-active pe ptides into delivery systems has been found to enhance intracellular d elivery of drugs including oligonucleotides, peptides, or plasmid DNA. In the majority of applications, the amphipathic peptides are designe d to act after uptake by endocytosis, releasing the delivered agent fr om intracellular vesicles to the cytoplasm. Alternatively, peptides mi ght mediate direct drug transfer across the plasma membrane. Although encouraging results have been obtained with the use of synthetic pepti des to enhance cellular delivery of various compounds, the naturally e volved mechanisms observed in the entry of viruses or protein toxins a re still far more efficient. For the development of improved synthetic peptides and carrier systems a better understanding of the molecular details of membrane-destabilization and reorganization will be essenti al. (C) 1998 Elsevier Science B.V. All rights reserved.