title: Transdermal absorption and stability enhancement of salmon calcitonin by Tat peptide.
abstract: BACKGROUND
  Highly organized structure of stratum corneum (SC) is the major barrier of the delivery of macromolecules such as proteins and peptides across the skin. Recently, cell penetrating peptides (CPPs) such as HIV1-trans-activating transcriptional (Tat) have been used to enhance the topical delivery of proteins and peptides.
  
  
  OBJECTIVE
  This study aimed to enhance the transdermal absorption and chemical stability of salmon calcitonin (sCT) by co-incubation with Tat.
  
  
  METHODS
  Tat-sCT mixture at 1:1 molar ratio was prepared. Transdermal absorption and chemical stability of the mixture was evaluated in comparing with free sCT.
  
  
  RESULTS
  Tat-sCT mixture gave higher cumulative amounts and fluxes of sCT than free sCT. The maximum percentage of sCT of 58.36 ± 12.33% permeated into the receiving chamber was found in Tat-sCT mixture at 6 h which was 3.50 folds of free sCT. Tat-sCT mixture demonstrated better sCT stability than sCT solution after 1 month storage at 4°C, 25°C and 45°C.
  
  
  CONCLUSIONS
  The positively-charged arginine groups in Tat might be responsible for the binding of peptide complexes to negatively charged cell surfaces by electrostatic interactions and also the translocation of sCT through the excised skin.
  
  
  CONCLUSIONS
  This study demonstrated the enhancements of transdermal absorption and stability of sCT by Tat peptide with potential for further application in transdermal delivery of other therapeutic peptides.
authors.affiliation: Faculty of Pharmacy, Chiang Mai University, Chiang Mai, Thailand. pmpti006@chiangmai.ac.th
authors.forename: Jiradej
authors.initials: J
authors.lastname: Manosroi
authors.forename: Warangkana
authors.initials: W
authors.lastname: Lohcharoenkal
authors.forename: Friedrich
authors.initials: F
authors.lastname: Götz
authors.forename: Rolf G
authors.initials: RG
authors.lastname: Werner
authors.forename: Worapaka
authors.initials: W
authors.lastname: Manosroi
authors.forename: Aranya
authors.initials: A
authors.lastname: Manosroi
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D050071:Bone Density Conservation Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D002116:Calcitonin / Q000737:chemistry / Q000493:pharmacokinetics*; D004338:Drug Combinations; D004355:Drug Stability; D015696:Gene Products, tat / Q000737:chemistry / Q000493:pharmacokinetics*; D008297:Male; D010316:Particle Size; D010446:Peptide Fragments / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption
chemical_list: D050071:Bone Density Conservation Agents; D004338:Drug Combinations; D015696:Gene Products, tat; D010446:Peptide Fragments; C028815:salmon calcitonin; D002116:Calcitonin