J. Cosmet. Sci., 70, 299–312 (November/December 2019) 299 Effect of Palmitic Acid Conjugation on Physicochemical Properties of Peptide KTTKS: A Preformulation Study SEYEDEH MARYAM MORTAZAVI, FARZAD KOBARFARD, HOWARD I. MAIBACH, and HAMID REZA MOGHIMI , Department of Pharmaceutics and Nanotechnology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran, 1991953381 (S.M.M., H.R.M.), Department of Medicinal Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran , 1991953381 (F.K.), Department of Dermatology, School of Medicine, University of California, San Francisco, California, 94115 (H.I.M.), Protein Technology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran, 1991953381 (H.R.M.) Accepted for publication September 21, 2019. Synopsis Lys–Thr–Thr–Lys–Ser (KTTKS) minimally crosses the skin because of hydrophilicity therefore, its palmitoyl derivative, palmitoyl-KTTKS (Pal-KTTKS), is used in cosmetic products. In spite of this, there is insuffi cient information on its physicochemical properties and the effects of palmitoylation on such properties. The aim of this study was to investigate these properties. Such information would help appropriate formulation development. KTTKS and Pal-KTTKS were synthesized and characterized for ultra violet (UV) absorption, structure [X-ray diffraction (XRD)], morphology (electron microscopy), birefringence (polarized light microscopy), partitioning, solubility, thermal behavior (melting, thermogravimetric analysis, and differential scanning calorimetry), surface activity, critical micelle concentration (CMC, by tensiometry), and stability. KTTKS and Pal-KTTKS decomposed at about 154 and 150°C, respectively, and did not show a melting point before decomposition. The maximum UV absorbance of peptides was less than 200 nm. Both peptides showed birefringence, irregular fl ake morphologies, and hygroscopicity. KTTKS was freely soluble in water at room temperature (logP = -1.6 ± 0.15), indicating its hydrophilic nature. logP of Pal-KTTKS was calculated to be about 3.7, indicating a lipophilic compound. Pal-KTTKS showed surface activity with a CMC value of 0.024 ± 0.004 mM (19.25 ± 2.9 mg/L), whereas KTTKS did not show such surface activity. Palmitoylation demonstrated sharp peaks in the XRD pattern of KTTKS. KTTKS and Pal-KTTKS differ mainly in terms of chemical properties and show some similarity in physical properties. These results can be used for formulation developments. INTRO D UCTION Skin aging prevention is an attractive issue in the cosmetic industry. Antiaging products include retinoids, alpha hydroxy acids, moisturizers, antioxidants (such as L-ascorbic acid, niacinamide, α-tocopherol, and ubiquinone), and peptides (1). Address all correspondence to Hamid Reza Moghimi at hrmoghimi@sbmu.ac.ir and hrmoghimi@yahoo.com.
JOURNAL OF COSMETIC SCIENCE 300 Based on their mechanism of action, topical peptides are classifi ed into four categories: signal peptides, enzyme-inhibitor peptides, neurotransmitter-affecting peptides, and car- rier peptides (1–4). Lys–Thr–Thr–Lys–Ser (KTTKS) (see Figure 1) is a signal peptide discovered by Katayama et al. in 1993. They demonstrated that extracellular matrix biosynthesis in human fetal lung fi broblasts was stimulated by KTTKS as a subfragment from C-peptides of type I procollagen, which is able to increase dermal remodeling (5). Despit e its high antiaging potential, this peptide minimally penetrates the skin. One strategy used to overcome this problem is conjugation to a lipophilic compound such as palmitic acid (a long-chain fatty acid containing 16 carbon atoms) (6). Palmitoyl-KTTKS (Pal-KTTKS) (see Figure 1) (brand name MatrixylTM, Sederma Inc., Le Perray-en-Yvelines, France) is available on the global market in antiaging formulations. Pal-KTTKS demon- strated improved effects on reduction of skin wrinkles in a 12-week, double-blind, placebo- controlled, clinical study on photoaged human facial skin (7). Fu et al. (8) demonstrated that niacinamide/Pal-KTTKS/retinyl propionate products had greater effect on improve- ment of wrinkle appearance than a 0.02% tretinoin product. Unfortu nately, only few preformulation studies exist on them. Lack of information about physicochemical proper- ties of these compounds leads to diffi culty in their formulation. Here, K TTKS and Pal-KTTKS were synthesized, and after confi rmation by mass spec- troscopy, physicochemical properties of both peptides and, therefore, the effects of covalent attachment of palmitic acid on KTTKS properties were investigated. To achieve these goals, ultra violet (UV) absorption ability, structure, morphology, birefringence, thermal Figure 1. Chemical stru c ture of KTTKS (A) and Pal-KTTKS (B).
Previous Page Next Page