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Thermosensitive dendritic polyglycerol-based nanogels for cutaneous delivery of biomacromolecules

Witting, M., Molina, M., Obst, K., Plank, R., Eckl, K.M., Hennies, Hans C., Calderon, M., Friess, W. and Hedtrich, S. (2015) Thermosensitive dendritic polyglycerol-based nanogels for cutaneous delivery of biomacromolecules. Nanomedicine, 11 (5). pp. 1179-1187. ISSN 1549-9634

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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 (~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.

Item Type: Article
Additional Information: Unmapped bibliographic data: ST - Thermosensitive dendritic polyglycerol-based nanogels for cutaneous delivery of biomacromolecules [Field not mapped to EPrints] AD - Ludwig-Maximilians University Munich, Department of Pharmacy, Munich, Germany. [Field not mapped to EPrints] AN - 25791808 [Field not mapped to EPrints]
Uncontrolled Keywords: Acrylic Resins/*chemistry
Subjects: Q Science > QH Natural history > QH301 Biology
Q Science > QH Natural history > QH426 Genetics
R Medicine > RL Dermatology
Schools: School of Applied Sciences
Depositing User: Hans Hennies
Date Deposited: 06 Jul 2016 10:54
Last Modified: 29 Jul 2016 13:01


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