Thermosensitive dendritic polyglycerol-based nanogels for cutaneous delivery of biomacromolecules

Item Type:	Article
Title:	Thermosensitive dendritic polyglycerol-based nanogels for cutaneous delivery of biomacromolecules
Creators Name:	Witting, M. and Molina, M. and Obst, K. and Plank, R. and Eckl, K.M. and Hennies, H.C. and Calderón, M. and Friess, W. and Hedtrich, S.
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 (~ 200 nm) 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.
Keywords:	Reconstructed human skin, Cutaneous protein delivery, Thermoresponsive nanogels, Dendritic polyglycerol, Skin barrier restoration, Animals, Cattle, Swine
Source:	Nanomedicine: Nanotechnology, Biology and Medicine
ISSN:	1549-9634
Publisher:	Elsevier
Volume:	11
Number:	5
Page Range:	1179-87
Date:	July 2015
Official Publication:	https://doi.org/10.1016/j.nano.2015.02.017
PubMed:	View item in PubMed

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