Opioid peptide drug development: transport of opioid chimeric peptides through the blood-brain barrier

The use of chimeric peptides and physiologic-based strategies for drug delivery through the BBB may be applied to opioid peptides (dynorphins, endorphin analogs, and enkephalin analogs), and these agents have considerable advantages in drug development with respect to drug addiction. Recent research has allowed for the development of efficacious BBB drug transport vectors, as well as the demonstration that these vectors allow for shuttling of opioid peptides through the BBB in vivo. The major challenge to future research is the development of coupling strategies that allow for the release of biologically active opioid peptide from the drug transport vector following its cleavage by disulfide reductase enzymes, which are abundant in brain. These coupling strategies must be developed in advance since the amino groups necessary for coupling are incorporated into the opioid peptide at the level of solid-state synthesis.