Cell-penetrating Peptide-biodrug Strategy for Oral and Nasal Delivery: Review of Recent Findings

Despite remarkable revolutionary progress in therapeutic biodrugs, such as peptides and proteins, the effective and convenient noninvasive delivery of this therapeutics remains a major challenge. Oral delivery of peptides and proteins remains an attractive alternative to parenteral delivery, and this has challenged various attempts at delivery development. Incorporation of new tools into the delivery systems to raise membrane permeability of biodrugs is essential to attain high oral bioavailability that is acceptable in clinical applications. In developing oral protein delivery systems with high bioavailability, three practical approaches might be most helpful: structural modification of biodrugs, conjugation of biofunctional moiety to biodrugs, or use of improved particulate delivery carriers. Therefore, we have currently developed feasible approach to improve the oral and nasal bioavailability of biodrugs with cell-penetrating peptides (CPPs) through the intestinal and nasal epithelial membranes. Further advantage of this promising strategy is that this successful noninvasive absorption could be achieved by more convenient methodology, coadministration of CPPs with biodrugs through intermolecular interaction among them. At the end of this review, we intend to show the absorption mechanism and pharmacokinetics of biodrugs, coadministered with the applicability of CPPs for noninvasive biodrugs delivery through the epithelial membrane.