Therapeutic Peptides in Aged Skin

By: Farzam Gorouhi, MD, and Howard I. Maibach, MD, University of California School of Medicine

Posted: August 28, 2009, from the September 2009 issue of Cosmetics & Toiletries.

Editor’s note: The following article is adapted from the Textbook on Aging Skin, a Springer compilation edited by HI Maibach, MA Farage and KW Miller, which currently is in press. Farzam Garouhi, MD, is a volunteer research scholar with Maibach at the University of California School of Medicine, San Francisco; he is also an author featured in the textbook.

In the year 2000, individuals over the age of 65 represented 13% of the US population, and this number is expected to increase to 20% by 2030. This increase in the number of older individuals over younger individuals will transform the shape of age distribution from what currently is graphed as a pyramid into a rectangle.¹ This demographic shift calls for increased efforts to prevent the aging process and to develop safe and effective drugs for the elderly.

In cosmetic dermatology, experts are exploring better anti-solar, antiaging, antiwrinkle and firming products. Pharmaceutical companies frequently use peptides as active ingredients in creams prescribed at medical and dermatology offices. Peptides can have different effects on the skin, especially for cosmetics purposes, but the most important concern regarding their topical use is their ability to penetrate skin.

Ideally, topical drugs have: a molecular weight less than 500 daltons; a moderate log of partition coefficient octanol/water between 1 and 3; a melting point of less than 200°C; a reasonable aqueous solubility (> 1 mg/mL); and few or no polar centers.^2,3 The diffusivity of molecules into the stratum corneum (SC) is related to the number of hydrogen-bonding groups on a molecule; maximal diffusivity is achieved with small non-hydrogen-bonding molecules while minimal diffusivity occurs with molecules containing four hydrogen-bonding groups.⁴

Peptides and proteins contain many amide bonds as hydrogen-bond donor and acceptor groups. Due to their large molecular size, they have low diffusivity in skin. Furthermore, they are often charged at a physiological pH, making them intrinsically hydrophilic and hence, the lipophilic SC is a significant barrier to their penetration.⁵