Universität zu Köln

Witting, Madeleine, Molina, Maria ORCID: 0000-0001-6139-6633, Obst, Katja, Plank, Roswitha, Eckl, Katja Martina, Hennies, Hans Christian, Calderon, Marcelo ORCID: 0000-0002-2734-9742, Friess, Wolfgang and Hedtrich, Sarah (2015). Thermosensitive dendritic polyglycerol-based nanogels for cutaneous delivery of biomacromolecules. Nanomed.-Nanotechnol. Biol. Med., 11 (5). S. 1179 - 1188. AMSTERDAM: ELSEVIER SCIENCE BV. ISSN 1549-9642

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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 degrees C, which is favorable for cutaneous applications due to the native thermal gradient of human skin. At >= 35 degrees C, the particle size (similar to 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. (C) 2015 Elsevier Inc. All rights reserved.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Witting, Madeleine UNSPECIFIED UNSPECIFIED UNSPECIFIED Molina, Maria UNSPECIFIED orcid.org/0000-0001-6139-6633 UNSPECIFIED Obst, Katja UNSPECIFIED UNSPECIFIED UNSPECIFIED Plank, Roswitha UNSPECIFIED UNSPECIFIED UNSPECIFIED Eckl, Katja Martina UNSPECIFIED UNSPECIFIED UNSPECIFIED Hennies, Hans Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Calderon, Marcelo UNSPECIFIED orcid.org/0000-0002-2734-9742 UNSPECIFIED Friess, Wolfgang UNSPECIFIED UNSPECIFIED UNSPECIFIED Hedtrich, Sarah UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-400520
DOI:	10.1016/j.nano.2015.02.017
Journal or Publication Title:	Nanomed.-Nanotechnol. Biol. Med.
Volume:	11
Number:	5
Page Range:	S. 1179 - 1188
Date:	2015
Publisher:	ELSEVIER SCIENCE BV
Place of Publication:	AMSTERDAM
ISSN:	1549-9642
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CELL-PENETRATING PEPTIDES; HUMAN SKIN; IN-VITRO; DRUG-DELIVERY; FILAGGRIN DEFICIENCY; DISEASED SKIN; NANOPARTICLES; ABSORPTION; BARRIER; MODEL Multiple languages Nanoscience & Nanotechnology; Medicine, Research & Experimental Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/40052