Thermosensitive dendritic polyglycerol-based nanogels for cutaneous delivery of biomacromolecules.

Abstract

Genetic skin diseases caused by mutations resulting in diminished protein synthesis could benefit from local substitution of the missing protein. Proteins, however, are excluded from topical applications due to their physicochemical properties. We prepared protein-loaded thermoresponsive poly(N-isopropylacrylamide)-polyglycerol-based nanogels exhibiting a thermal trigger point at 35°C, which is favorable for cutaneous applications due to the native thermal gradient of human skin. At≥35°C, the particle size (~200nm) was instantly reduced by 20% and 93% of the protein was released; no alterations of protein structure or activity were detected. Skin penetration experiments demonstrated efficient intraepidermal protein delivery particularly in barrier deficient skin, penetration of the nanogels themselves was not detected. The proof of concept was provided by transglutaminase 1-loaded nanogels which efficiently delivered the protein into transglutaminase 1-deficient skin models resulting in a restoration of skin barrier function. In conclusion, thermoresponsive nanogels are promising topical delivery systems for biomacromolecules.

FROM THE CLINICAL EDITOR:

Many skin disorders are characterized by an absence of a specific protein due to underlying gene mutation. In this article, the authors described the use of a thermoresponsive PNIPAM-dPG nanogel for cutaneous protein delivery in a gene knock-down model of human skin. The results may have implication for nano-based local delivery of therapeutic agents in skin.

• Authors: Madeleine Witting, Maria Molina, Katja Obst, Roswitha Plank, Katja Martina Eckl, Hans Christian Hennies, Marcelo Calderón, Wolfgang Friess, Sarah Hedtrich
• Journal: Nanomedicine : nanotechnology, biology, and medicine (Nanomedicine) Vol. 11 Issue 5 Pg. 1179-87 (Jul 2015) ISSN: 1549-9642 [Electronic] United States
• PMID: 25791808 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• Acrylic Resins
• Delayed-Action Preparations
• Gels
• Polymers
• poly-N-isopropylacrylamide
• polyglycerol
• Serum Albumin, Bovine
• Testosterone
• Transglutaminases
• transglutaminase 1
• Asparaginase
• Glycerol

Topics

• Acrylic Resins (chemistry)
• Administration, Cutaneous
• Animals
• Asparaginase (administration & dosage, pharmacokinetics)
• Cattle
• Delayed-Action Preparations (chemistry, metabolism)
• Gels (chemistry, metabolism)
• Gene Knockdown Techniques
• Glycerol (chemistry, metabolism)
• Humans
• Polymers (chemistry, metabolism)
• Serum Albumin, Bovine (administration & dosage, pharmacokinetics)
• Skin (metabolism, ultrastructure)
• Skin Absorption
• Swine
• Temperature
• Testosterone (administration & dosage, pharmacokinetics)
• Transglutaminases (administration & dosage, genetics, pharmacokinetics)