Thermosensitive dendritic polyglycerol-based nanogels for cutaneous delivery of biomacromolecules

Madeleine Witting, Maria Molina, Katja Obst, Roswitha Plank, Katja Martina Eckl, Hans Christian Hennies, Marcelo Calderón, Wolfgang Friess, Sarah Hedtrich

Research output: Contribution to journalArticle

39 Citations (Scopus)

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.
LanguageEnglish
Pages1179-1187
Number of pages9
JournalNanomedicine: Nanotechnology, Biology, and Medicine
Volume11
Issue number5
Early online date16 Mar 2015
DOIs
Publication statusPublished - Jul 2015
Externally publishedYes

Fingerprint

Proteins
Skin
Genetic Skin Diseases
Hot Temperature
Trigger Points
NanoGel
polyglycerol
Particle Size
Thermal gradients
Restoration
Substitution reactions
Particle size
Mutation
Experiments
transglutaminase 1

Cite this

Witting, Madeleine ; Molina, Maria ; Obst, Katja ; Plank, Roswitha ; Eckl, Katja Martina ; Hennies, Hans Christian ; Calderón, Marcelo ; Friess, Wolfgang ; Hedtrich, Sarah. / Thermosensitive dendritic polyglycerol-based nanogels for cutaneous delivery of biomacromolecules. In: Nanomedicine: Nanotechnology, Biology, and Medicine. 2015 ; Vol. 11, No. 5. pp. 1179-1187.
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Thermosensitive dendritic polyglycerol-based nanogels for cutaneous delivery of biomacromolecules. / Witting, Madeleine; Molina, Maria; Obst, Katja; Plank, Roswitha; Eckl, Katja Martina; Hennies, Hans Christian; Calderón, Marcelo; Friess, Wolfgang; Hedtrich, Sarah.

In: Nanomedicine: Nanotechnology, Biology, and Medicine, Vol. 11, No. 5, 07.2015, p. 1179-1187.

Research output: Contribution to journalArticle

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T1 - Thermosensitive dendritic polyglycerol-based nanogels for cutaneous delivery of biomacromolecules

AU - Witting, Madeleine

AU - Molina, Maria

AU - Obst, Katja

AU - Plank, Roswitha

AU - Eckl, Katja Martina

AU - Hennies, Hans Christian

AU - Calderón, Marcelo

AU - Friess, Wolfgang

AU - Hedtrich, Sarah

N1 - No full text in Eprints. HN 14/11/2017

PY - 2015/7

Y1 - 2015/7

N2 - 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.

AB - 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.

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KW - Gene Knockdown Techniques

KW - Glycerol

KW - Humans

KW - Polymers

KW - Serum Albumin, Bovine

KW - Skin

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KW - Swine

KW - Temperature

KW - Testosterone

KW - Transglutaminases

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

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