INTRODUCTION
Most physiological processes in the body are regulated by the interaction of specific amino acid sequences, functioning either as peptides or fragments of proteins. Peptides are compounds containing two or more amino acids linked by an amide bond that transmit biochemical signals.1 Synthetic engineering of bioactive peptides allows for the targeted promotion of physiological processes while minimizing associated side effects (Table 1). By substituting amino acids, diverse peptide analogs are created to regulate the potency, solubility, toxicity, and cost of potential therapies.2 The ability to modify and control peptide compounds with ease is unique, as many other biological molecules are chemically challenging to alter. Consequently, bioactive peptides offer not only a broad array of potential active ingredients, but also can be developed and tailored to be made suitable for specific indications and demographics.3
Peptide Delivery
Although many advancements in peptide synthesis and therapeutic use have been made in recent decades, delivery to target sites is still a challenge. Peptides are often administered parenterally since they are unstable when administered orally due to first-pass degradation/metabolism. Yet, the typically short half-life of peptides requires frequent injections, thus alternative routes of delivery are being actively researched. Transdermal delivery is a promising alternative as this route encounters less enzymatic degradation; however, the greatest impediment is the actual target - the formidable skin barrier.4
Peptides require active methods of delivery through the skin given they are typically large molecular weight (>500 Da), polar and hydrophilic molecules. One approach to improve active diffusion is with the use of physical or chemical permeation enhancers.4-6 Encapsulation within polymeric particulate delivery systems, such as phospholipid-based liposomes, which are known to penetrate the skin more easily, can improve topical delivery. Moreover, chemical modification of peptides through the addition of lipophilic derivatives is a strategy to increase encapsulation efficiency. Physical penetration enhancers include application of energy to drive delivery of peptides (iontophoresis, electroporation, or sonophoresis), minimally invasive disruption of the stratum corneum (microneedles, jet injectors), and ablation of the stratum corneum (lasers, radiofrequency, suction blister, thermal poration). Innovative technologies continue to be researched for transdermal delivery of peptides, particularly novel combinations of enhancement techniques which show promise in delivery optimization by leveraging synergistic mechanisms.4
Dermatologic Applications
Skin Aging
In the current era, significant efforts and research are driving the development of peptides targeting skin aging, generating a robust market in the cosmeceutical industry for peptide innovation. Ex vivo and translational studies have demonstrated that bioactive peptides increase fibroblast production of collagen, decrease collagen breakdown, and increase extracellular matrix protein expression, maintaining the skin's structural integrity and combating the natural aging process.7-9 Additionally, peptides promote anti-aging by scavenging free radicals, chelating pro-oxidative transition metals, decreasing hydroperoxides, and enzymatically eliminating certain oxidants.10 Currently, there are four categories of anti-ageing peptides with varying primary mechanistic processes: signal peptides, neurotransmitter-affecting peptides, carrier peptides, and antioxidants (Table 2).10
Acne
Oral antibiotics are commonly employed in the treatment of moderate to severe inflammatory acne, however long-term
Oral antibiotics are commonly employed in the treatment of moderate to severe inflammatory acne, however long-term
