title: Heptapeptide-loaded solid lipid nanoparticles for cosmetic anti-aging applications.
abstract: The cosmetic industry requires more and more expensive actives and ingredients such as retinol, coenzyme Q10, proteins, peptides and biotechnologically produced molecules. In this study, we demonstrate the development of a cost effective formulation of a nanostructured lipid carrier (NLC) or solid lipid nanoparticles (SLN) improving peptide delivery into skin. NLC or SLN are very suitable vehicles for the delivery of active ingredients into skin. The SLN, produced by using hot high pressure homogenization method combine advantages such as physical stability, protection of incorporated labile actives and controlled release. By the used method we dispersed the amorphous heptapeptide DEETGEF in shea butter and homogenized this pre-dispersion at 60°C together with the water phase using a Microfluidizer at 1000bar. The analysis of the obtained SLN-P7 showed a particle size of 173nm, incorporated peptide of 0.014%, entrapment efficiency of 90.8%, melting peak (DSC) of the core lipid of 27°C and a zeta potential of -54mV. By an ex vivo study with skin explants we could stimulate NQO1 (NAD(P)H quinone oxidoreductase), HMOX1 (Heme oxygenase-1) and PRDX1 (Peroxiredoxin-1) genes all of which are cell protecting enzymes. In a multicellular protection against UV induced stress study with skin explants we detected the formation of sun burn cells and the number and morphology of Langerhans cells. The application of our SLN-P7 formulation on skin explants led to a significant and dose dependent protection against UV irradiation. In the clinical suction blister study, irradiation with UVA light for two hours after final product application led to a statistically significant increase of the 8-OhdG (8-hydroxy-2'-deoxyguanosine) concentration in the human epidermis. The skin treated with our verum formulation showed a statistically significant 20% decrease in DNA damage compared to placebo. In conclusion, it was demonstrated that SLN technology enabled peptide delivery into skin allowing it to perform protective functions.
authors.affiliation: Mibelle Biochemistry, Bolimattstrasse 1, CH 5033 Buchs, Switzerland. Electronic address: franz.suter@mibellegroup.com.
authors.forename: Franz
authors.initials: F
authors.lastname: Suter
authors.affiliation: Mibelle Biochemistry, Bolimattstrasse 1, CH 5033 Buchs, Switzerland.
authors.forename: Daniel
authors.initials: D
authors.lastname: Schmid
authors.affiliation: Mibelle Biochemistry, Bolimattstrasse 1, CH 5033 Buchs, Switzerland.
authors.forename: Franziska
authors.initials: F
authors.lastname: Wandrey
authors.affiliation: Mibelle Biochemistry, Bolimattstrasse 1, CH 5033 Buchs, Switzerland.
authors.forename: Fred
authors.initials: F
authors.lastname: Zülli
mesh_terms: D000287:Administration, Topical; D000328:Adult; D020816:Amino Acid Motifs; D002152:Calorimetry, Differential Scanning; D003358:Cosmetics / Q000008:administration & dosage*; D004249:DNA Damage; D004311:Double-Blind Method; D004337:Drug Carriers / Q000737:chemistry; D004817:Epidermis / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D044085:Microfluidics; D046529:Microscopy, Electron, Transmission; D008875:Middle Aged; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D010455:Peptides / Q000737:chemistry*; D054464:Peroxiredoxins / Q000378:metabolism; D011312:Pressure; D012867:Skin / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects; D012869:Skin Absorption; D015595:Skin Aging / Q000187:drug effects*; D013696:Temperature; D014466:Ultraviolet Rays; D014867:Water
chemical_list: D003358:Cosmetics; D004337:Drug Carriers; D008055:Lipids; D010455:Peptides; D014867:Water; C515940:PRDX1 protein, human; D054464:Peroxiredoxins; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human
keywords: Cosmetic; Keap1; Nrf2; Peptide delivery; SLN; Skin; Solid lipid nanoparticles