Challenges and Strategies for Topical and Transdermal Delivery of Bioactive Peptides

Bioactive peptides have gained the attention and interest of researchers and the industry for their therapeutic effects and high specificity, thus reducing the risks of side effects and making them an attractive alternatives in developing new biopharmaceuticals or cosmeceuticals. Nevertheless, their incorporation into formulations and administration presents challenges such as low stability under different storage conditions and gastrointestinal degradation after oral delivery. Likewise, the parenteral route is an invasive method that is painful and therefore reduces patient compliance. Topical delivery of bioactive peptides is a painless noninvasive alternative to reduce peptide degradation, exert local effects in the applied area, and improve patient compliance. In this review, we discuss the physicochemical properties of peptides and the mechanisms involved in their degradation. In addition, the most important aspects of skin structure and skin permeation routes, and the requirements for topical and transdermal drug delivery are also discussed in this article. Finally, nanocarrier development advances for the topical delivery of peptides (water-in-somes, and microneedles) and other strategies, such as metal complexation, cell-penetrating peptides, and synthetic modification, are also reviewed. All these topics consider the perspective of their effect to improve skin permeability to peptides and their stability over time during storage.