title: Microneedle-Mediated Delivery of Copper Peptide Through Skin.
abstract: OBJECTIVE
  Copper peptide (GHK-Cu) plays an important role in skin regeneration and wound healing. However, its skin absorption remains challenging due to its hydrophilicity. Here we use polymeric microneedle array to pre-treat skin to enhance GHK-Cu skin penetration.
  
  
  METHODS
  Two in vitro skin models were used to assess the capability of microneedles in facilitating skin delivery of GHK-Cu. Histological assay and confocal laser scanning microscopy were performed to characterize and quantify the microconduits created by the microneedles inside skin. Cellular and porcine models were used to evaluate the safety of microneedle-assisted copper peptide delivery.
  
  
  RESULTS
  The depth and percentage of microneedle penetration were correlated with application forces, which in turn influenced the extent of enhancement in the skin permeability of GHK-Cu. In 9 h, 134 ± 12 nanomoles of peptide and 705 ± 84 nanomoles of copper permeated though the microneedle treated human skin, while almost no peptide or copper permeated through intact human skin. No obvious signs of skin irritation were observed with the use of GHK-Cu after microneedle pretreatment.
  
  
  CONCLUSIONS
  It is effective and safe to enhance the skin permeation of GHK-Cu by using microneedles. This approach may be useful to deliver similar peptides or minerals through skin.
authors.affiliation: Department of Pharmacy, National University of Singapore, 18 Science Drive 4, Singapore, Singapore, 117543.
authors.forename: Hairui
authors.initials: H
authors.lastname: Li
authors.forename: Yong Sheng Jason
authors.initials: YS
authors.lastname: Low
authors.forename: Hui Ping
authors.initials: HP
authors.lastname: Chong
authors.forename: Melvin T
authors.initials: MT
authors.lastname: Zin
authors.forename: Chi-Ying
authors.initials: CY
authors.lastname: Lee
authors.forename: Bo
authors.initials: B
authors.lastname: Li
authors.forename: Melvina
authors.initials: M
authors.lastname: Leolukman
authors.forename: Lifeng
authors.initials: L
authors.lastname: Kang
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003300:Copper / Q000008:administration & dosage* / Q000737:chemistry; D015194:Diffusion Chambers, Culture; D016503:Drug Delivery Systems; D006801:Humans; D066298:In Vitro Techniques; D007509:Irritants; D015603:Keratinocytes / Q000187:drug effects; D009339:Needles; D009842:Oligopeptides / Q000008:administration & dosage* / Q000737:chemistry; D051381:Rats; D012867:Skin / Q000473:pathology; D012869:Skin Absorption; D013552:Swine
chemical_list: D007509:Irritants; D009842:Oligopeptides; C020905:glycyl-histidyl-lysine; D003300:Copper