Macromolecular drugs (e.g., proteins and nucleic acids) are highly environmentally liable and unstable, and
their administration is strictly limited to injection. Moreover, a vast majority of macromolecules are cell membrane-
impermeable, and it is a critical issue to enhance the cellular uptake efficiency for improving the treatment outcomes.
Cell-penetrating peptide (CPP)-assisted strategy is promising for effective macromolecular delivery. As a case in point,
CPP-mediated protein delivery has been considered as a revolutionary breakthrough. With aid of CPP, virtually all pro-
teins can become cell-permeable. Generally, CPP-protein delivery works in a covalent delivery pattern, by which CPP and
its cargo are linked via covalent bond. Recently, noncovalent delivery has also attracted attention for its potential application for protein delivery. In the presented work, the noncovalent pattern was demonstrated for its feasibi
lity in percutaneous and nose-to-brain delivery with TAT/GFP as model drug, in comparison with the covalent method. Noncovalent
CPP/protein delivery and its noninvasive application may provide a facile method for protein therapy.
Keywords: Cell-penetrating peptide, noncovalent, nose-to-brain delivery, percutaneous delivery, protein delivery, TAT.
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