31P solid-state NMR based monitoring of permeation of cell penetrating peptides into skin |
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Institution: | 1. Dept. of Clinical Veterinary Medicine, University of Bern, Switzerland;2. Dept. of Clinical Research and Radiology, University of Bern, Switzerland;3. Dept. of Clinical Research and Veterinary Public Health, University of Bern, Switzerland;4. Dept. of Chemistry & Biochemistry, University of Bern, Switzerland;1. Biopharmaceutics and Pharmaceutical Technology, Saarland University, Saarbruecken, Germany;2. Philipps University Marburg, Pharmaceutical Technology and Biopharmacy, Marburg, Germany;3. Department of Dermatology, Saarland University Hospital, Homburg/Saar, Germany;4. Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Center for Infection Research, Saarbruecken, Germany |
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Abstract: | The main objective of the current study was to investigate penetration of cell penetrating peptides (CPPs: TAT, R8, R11, and YKA) through skin intercellular lipids using 31P magic angle spinning (MAS) solid-state NMR. In vitro skin permeation studies were performed on rat skin, and sections (0–60, 61–120, and 121–180 μm) were collected and analyzed for 31P NMR signal. The concentration-dependent shift of 0, 25, 50, 100, and 200 mg/ml of TAT on skin layers, diffusion of TAT, R8, R11, and YKA in the skin and time dependent permeation of R11 was measured on various skin sections using 31P solid-state NMR. Further, CPPs and CPP-tagged fluorescent dye encapsulate liposomes (FLip) in skin layers were tagged using confocal microscopy. The change in 31P NMR chemical shift was found to depend monotonically on the amount of CPP applied on skin, with saturation behavior above 100 mg/ml CPP concentration. R11 and TAT caused more shift in solid-state NMR peaks compared to other peptides. Furthermore, NMR spectra showed R11 penetration up to 180 μm within 30 min. The results of the solid-state NMR study were in agreement with confocal microscopy studies. Thus, 31P solid-state NMR can be used to track CPP penetration into different skin layers. |
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Keywords: | Topical delivery Cell penetrating peptides Solid-state NMR TAT peptide Polyarginine peptide Skin permeation Confocal laser scanning microscopy |
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