Department of Pharmaceutics and Pharmaceutical Nanotechnology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Protein Technology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Int J Cosmet Sci. 2022 Apr;44(2):232-248. doi: 10.1111/ics.12770. Epub 2022 Apr 28.
The skin offers various benefits and potential for peptide delivery if its barrier performance can be reduced temporarily and reversibly. As peptides possess high molecular weight, hydrophilic nature (in most cases), and ionizable groups in the structure, their skin delivery is highly challenging. Apart from this, they are susceptible to the proteolytic enzymes in the skin. Anti-wrinkle peptides, like other peptides, suffer from insufficient skin permeability, while most of them must penetrate deep in the skin to present their efficacy. Although the cellular studies indicate the effectiveness of such peptides, without the ability to permeate the skin sufficiently, this efficacy is useless. Poor skin permeability of anti-wrinkle peptides has led to ongoing research for finding feasible and noninvasive enhancement methods that would be desirable for consumers of cosmetic products.
In this paper, the possibility of skin permeation of anti-wrinkle peptides as well as the chemical, physical, and encapsulation approaches that have been employed to date to increase permeability of these difficult molecules are thoroughly reviewed.
Most anti-wrinkle peptides are not appropriate candidates for skin permeation and the use of enhancement methods is essential to increase their permeability. To do so, only some permeability enhancement approaches have been applied so far, including chemical modification with hydrophobic moieties or cell penetrating peptides, metal complexation, chemical permeation enhancers, iontophoresis, microneedles, and encapsulation in nanocarriers. The results of studies published on the skin permeability of anti-wrinkle peptides carnosine, GHK, PKEK, GEKG, GQPR, and KTTKS indicate that the skin permeability of these peptides can be successfully increased.
Although the skin permeability of most anti-wrinkle peptides is not high enough and most anti-wrinkle peptides might not reach their targets in the skin at right concentrations, their permeability can be increased to therapeutic concentrations using various enhancement approaches.
如果皮肤的屏障性能能够暂时且可逆地降低，那么皮肤可为肽类药物传递提供多种益处和潜力。由于肽类药物具有高分子量、亲水性（在大多数情况下）和结构中带可离子化基团的特点，因此其经皮传递极具挑战性。除此之外，它们还容易受到皮肤中蛋白水解酶的影响。除皱肽与其他肽类一样，存在皮肤渗透性不足的问题，而大多数除皱肽必须深入皮肤才能发挥功效。尽管细胞研究表明了这些肽类的有效性，但如果没有足够的透皮能力，这种有效性将毫无意义。除皱肽的皮肤渗透性差导致人们一直在研究可行的非侵入性增强方法，这对于化妆品的消费者来说是非常理想的。
本文全面回顾了作为化妆品使用的除皱肽的透皮可能性，以及迄今为止为提高这些难穿透分子的渗透性而采用的化学、物理和包封方法。
大多数除皱肽不适合透皮，必须采用增强方法来提高其渗透性。到目前为止，仅应用了一些通透性增强方法，包括用疏水性基团或细胞穿透肽进行化学修饰、金属络合、化学渗透增强剂、离子电渗、微针和纳米载体包封。已发表的关于除皱肽肉碱、GHK、PKEK、GEKG、GQPR 和 KTTKS 的皮肤渗透性研究结果表明，这些肽的皮肤渗透性可以成功提高。
虽然大多数除皱肽的皮肤渗透性不够高，而且大多数除皱肽可能无法以正确的浓度到达皮肤的靶标，但可以使用各种增强方法将其渗透性提高到治疗浓度。
