1. Dermal peptide delivery using enhancer molecules and colloidal carrier systems--part I: carnosine
A S B Goebel, G Schmaus, R H H Neubert, J Wohlrab Skin Pharmacol Physiol. 2012;25(6):281-7. doi: 10.1159/000341085. Epub 2012 Aug 7.
Due to the lipophilic properties of the uppermost skin layer of the stratum corneum (SC), it is highly challenging to attain therapeutic concentrations of active substances; hydrophilic drugs, in particular, penetrate poorly. The purpose of this study was the improvement of the topical bioavailability of the hydrophilic dipeptides L-carnosine and its related compound N-acetyl-L-carnosine. Different strategies were investigated. On the one hand, an enhancer molecule, 1,2-pentylene glycol (PG), was added to a standard preparation, and on the other hand, a microemulsion (ME-PG) system was developed. Both were compared to the standard formulation without an enhancer molecule. For all 3 preparations, the penetration of the peptides in ex vivo human skin was investigated. This allows statements to be made regarding dermal penetration, localization and distribution of the active substances in each skin layer as well as the influence of vehicle variations, in this case, the addition of PG or the incorporation of N-acetyl-L-carnosine in an ME-PG system. For L-carnosine and N-acetyl-L-carnosine, the use of the standard preparation with PG resulted in a significant increase of the substance within the SC. Approximately 6-fold and higher dipeptide concentrations in the SC and in the viable skin layers were detected at all experimental periods compared to the formulation without the enhancer molecule and the ME-PG. High concentrations of the compounds were found after a short period of time in the viable skin layers after applying the enhancer molecule, even in concentrations of 5%. The application of the colloidal carrier system did not lead to a higher penetration rate of N-acetyl-L-carnosine in comparison to both standard preparations, although it must be said that the microstructure of the investigated ME-PG might not have been optimal for the hydrophilic properties of the dipeptide.
2. Final report of the amended safety assessment of Glyceryl Laurate, Glyceryl Laurate SE, Glyceryl Laurate/Oleate, Glyceryl Adipate, Glyceryl Alginate, Glyceryl Arachidate, Glyceryl Arachidonate, Glyceryl Behenate, Glyceryl Caprate, Glyceryl Caprylate, Glyceryl Caprylate/Caprate, Glyceryl Citrate/Lactate/Linoleate/Oleate, Glyceryl Cocoate, Glyceryl Collagenate, Glyceryl Erucate, Glyceryl Hydrogenated Rosinate, Glyceryl Hydrogenated Soyate, Glyceryl Hydroxystearate, Glyceryl Isopalmitate, Glyceryl Isostearate, Glyceryl Isostearate/Myristate, Glyceryl Isostearates, Glyceryl Lanolate, Glyceryl Linoleate, Glyceryl Linolenate, Glyceryl Montanate, Glyceryl Myristate, Glyceryl Isotridecanoate/Stearate/Adipate, Glyceryl Oleate SE, Glyceryl Oleate/Elaidate, Glyceryl Palmitate, Glyceryl Palmitate/Stearate, Glyceryl Palmitoleate, Glyceryl Pentadecanoate, Glyceryl Polyacrylate, Glyceryl Rosinate, Glyceryl Sesquioleate, Glyceryl/Sorbitol Oleate/Hydroxystearate, Glyceryl Stearate/Acetate, Glyceryl Stearate/Maleate, Glyceryl Tallowate, Glyceryl Thiopropionate, and Glyceryl Undecylenate
Int J Toxicol. 2004;23 Suppl 2:55-94. doi: 10.1080/10915810490499064.
The safety of 43 glyceryl monoesters listed as cosmetic ingredients was reviewed in a safety assessment completed in 2000. Additional safety test data pertaining to Glyceryl Rosinate and Glyceryl Hydrogenated Rosinate were received and served as the basis for this amended report. Glyceryl monoesters are used mostly as skin-conditioning agents--emollients and/or surfactant--emulsifying agents in cosmetics.
3. Dermal peptide delivery using enhancer moleculs and colloidal carrier systems. Part II: Tetrapeptide PKEK
Reinhard H H Neubert, Elfi Sommer, Melanie Schölzel, Benjamin Tuchscherer, Yahja Mrestani, Johannes Wohlrab Eur J Pharm Biopharm. 2018 Mar;124:28-33. doi: 10.1016/j.ejpb.2017.12.004. Epub 2017 Dec 14.
Due to the lipophilic properties of the uppermost skin layer of the stratum corneum (SC) it is highly challenging to reach therapeutic concentrations of cosmetic actives and drugs. Particularly, the hydrophilic ones penetrate poorly across the SC. The purpose of this study was to improve the topical bioavailability of the hydrophilic, polar tetrapeptide PKEK (amino acid sequence in one-letter notation). A nano-sized carrier system (microemulsion, ME) was therefore developed since MEs provide excellent penetration enhancing properties. The penetration of PKEK from the ME was compared to the penetration from a standard formulation. For the two preparations the penetration of the tetrapeptide in ex vivo human skin was investigated. This allows to make statements regarding dermal penetration, localization and distribution of the active substances in each skin layer as well as the influence of vehicle variations, in this case the incorporation of PKEK into a ME system. Relatively high amounts between 40 and 58% of the tetrapeptide PKEK penetrated from the standard cream into the skin. The major proportion of PKEK, which penetrated from the standard cream, remained in the SC and did not reach the target compartment within the skin. Penetration of PKEK from the ME was comparable with the cream for the shortest test time. However, very high PKEK amounts penetrated form the nano-sized carrier system (ME) into the human skin after 100 min (94%) and after 300 min (88%). The largest proportion did not remain in the skin, but permeated into the acceptor compartment. Therefore, the relative peptide content in the viable skin layers was predominantly comparable for the cream and the ME. For some samples a tendency could be observed that slightly higher amounts of PKEK were detected after the application of the standard cream. The absolute peptide concentrations gave a similar conclusion. The results indicate that liquid nano-sized systems are very effective carriers for extremely hydrophilic peptides used in cosmetics and also in therapeutics.
