Tetrapeptide-30 (skin lightening peptide)

Krutmann, Jean, et al. British Journal of Dermatology, 2023, 188(2), 168-175.

Skin that is colored or colored in skin is most prone to UV-induced skin damage, such as photodermatosis and photoaging changes, and pigmentation disorders. Colored skin is naturally more protected from UVB but these communities are at higher risk for pigmented disorders.
The sunscreens for darker skin should not just be UVB/UVA2 resistant, but also UVA1 and the visible light to prevent pigmentation. UVA1 can lead to photoaging, and there's even been recent research pointing to the possibility that visible light plays a role in photoaging, and shorter wavelength blue light tends to be most destructive. The table to the right summarizes the characteristics of sunscreen formulations recommended for people of color.
Tetrapeptide-30: A synthetic peptide made of glutamic acid, lysine and proline that inhibits tyrosinase. Multiple studies have also indicated that tetrapeptide-30 can make Asian skin more even in color, and lessen melasma and PIH in V-VI people. In sunscreens formulated for people of color, tetrapeptide-30 is recommended as a depigmentant to optimize the therapy of patients with hyperpigmentation.

Neubert, Reinhard HH, et al. European Journal of Pharmaceutics and Biopharmaceutics, 2018, 124, 28-33.

For better topical bioavailability of hydrophilic polar tetrapeptide-30 (tetrapeptide PKEK), a nanoscale carrier system (microemulsion, ME) was developed due to ME's excellent penetration capabilities.
· Formulations
Standard formulation ingredient: 3.0% polyglyceryl-3-methylglucose distearate, 1.0% stearyl alcohol, 2.0% glyceryl stearate, 9.5% C12-15 alkyl benzoate, 9.5% caprylic/capric triglyceride, 0.8% Microcare MEM (methylisothiazolinone, methylparaben), 50% water, 25% active ingredient blend (2% tetrapeptide PKEK, 6% butylene glycol, 82% water, 10% glycerol).
In the colloidal carrier system (w/o ME), 0.5% tetrapeptide PKEK was dissolved in a 10% mixture of water and butylene glycol (1:1 w/w), which served as the hydrophilic phase. Next, 16.7% polyglyceryl-4 laurate and 8.3% sorbitan oleate were added, along with 65% oil component (isopropyl palmitate). The mixture was then shaken in a laboratory shaker until fully dissolved, resulting in a clear formulation with a yellow to amber hue.
· Tetrapeptide-30 microemulsion properties
In the shortest tested time, the penetration of PKEK in the ME was comparable to that of a standard cream. However, very high amounts of PKEK permeated from the nanocarrier system (ME) into human skin after 100 min (94%) and after 300 min (88%). The largest proportion did not remain in the skin but rather permeated into the receptor compartment. These results illustrate that liquid nanosystems are very effective carriers of extremely hydrophilic peptides used in cosmetics and therapeutics.