Efficient skin permeation of soluble proteins via flexible and functional nano-carrier

J Control Release. 2012 Jan 30;157(2):272-8. doi: 10.1016/j.jconrel.2011.08.013. Epub 2011 Aug 16.

Abstract

In spite of several intrinsic and distinct advantages, a topical and transdermal administration of drugs has been limited mainly due to very low permeability of drugs across skin. Especially, it is generally regarded that hydrophilic macromolecules such as proteins, peptides, and vaccines cannot penetrate across skin. In this study, we demonstrated that chitosan-conjugated, Pluronic-based nano-carrier (nanogel) can act as an efficient delivery vehicle of hydrophilic proteins across human skin. The functional nano-carrier (<100 nm in size), chemically-crosslinking Pluronic F 127 with chitosan conjugation, is flexible and soft with reservoir characteristics for biomacromolecules. The in-vitro permeation experiments through human cadaver skin revealed remarkable permeability of hydrophilic proteins of various sizes including FITC-BSA (67 kDa) and FITC-Insulin (6 kDa) by direct penetration of the nano-carrier across skin. The bioactivity post-permeation of proteins via the functional nano-carrier was also confirmed by delivering ß-galactosidase. Results presented in this paper suggest the use of chitosan-conjugated flexible nano-carrier as a novel platform for transcutaneous delivery of hydrophilic macromolecules and other drug-delivery applications.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Cutaneous
  • Chitosan / administration & dosage*
  • Chitosan / chemistry
  • Drug Carriers / administration & dosage*
  • Drug Carriers / chemistry
  • Fluorescein-5-isothiocyanate / administration & dosage
  • Fluorescein-5-isothiocyanate / analogs & derivatives*
  • Fluorescein-5-isothiocyanate / chemistry
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • In Vitro Techniques
  • Insulin / administration & dosage
  • Insulin / analogs & derivatives*
  • Insulin / chemistry
  • Male
  • Middle Aged
  • Nanostructures / administration & dosage
  • Nanostructures / chemistry
  • Permeability
  • Poloxamer / administration & dosage*
  • Poloxamer / chemistry
  • Serum Albumin, Bovine / administration & dosage*
  • Serum Albumin, Bovine / chemistry
  • Skin / metabolism*
  • Skin Absorption

Substances

  • Drug Carriers
  • Insulin
  • fluorescein isothiocyanate bovine serum albumin
  • insulin, fluorescein-isothiocyanated-
  • Poloxamer
  • Serum Albumin, Bovine
  • Chitosan
  • Fluorescein-5-isothiocyanate