dc.contributor.author
Giulbudagian, M.
dc.contributor.author
Yealland, G.
dc.contributor.author
Hönzke, S.
dc.contributor.author
Edlich, A.
dc.contributor.author
Geisendörfer, B.
dc.contributor.author
Kleuser, B.
dc.contributor.author
Hedtrich, S.
dc.contributor.author
Calderón, M.
dc.date.accessioned
2018-06-08T10:53:24Z
dc.date.available
2017-11-23T08:51:30.638Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/21281
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-24576
dc.description.abstract
Topical administration permits targeted, sustained delivery of therapeutics to
human skin. Delivery to the skin, however, is typically limited to lipophilic
molecules with molecular weight of < 500 Da, capable of crossing the stratum
corneum. Nevertheless, there are indications protein delivery may be possible
in barrier deficient skin, a condition found in several inflammatory skin
diseases such as psoriasis, using novel nanocarrier systems. Methods: Water in
water thermo-nanoprecipitation; dynamic light scattering; zeta potential
measurement; nanoparticle tracking analysis; atomic force microscopy;
cryogenic transmission electron microscopy; UV absorption; centrifugal
separation membranes; bicinchoninic acid assay; circular dichroism; TNFα
binding ELISA; inflammatory skin equivalent construction; human skin biopsies;
immunohistochemistry; fluorescence microscopy; western blot; monocyte derived
Langerhans cells; ELISA Results: Here, we report the novel synthesis of
thermoresponsive nanogels (tNG) and the stable encapsulation of the anti-TNFα
fusion protein etanercept (ETR) (~150 kDa) without alteration to its
structure, as well as temperature triggered release from the tNGs. Novel tNG
synthesis without the use of organic solvents was conducted, permitting in
situ encapsulation of protein during assembly, something that holds great
promise for easy manufacture and storage. Topical application of ETR loaded
tNGs to inflammatory skin equivalents or tape striped human skin resulted in
efficient ETR delivery throughout the SC and into the viable epidermis that
correlated with clear anti-inflammatory effects. Notably, effective ETR
delivery depended on temperature triggered release following topical
application. Conclusion: Together these results indicate tNGs hold promise as
a biocompatible and easy to manufacture vehicle for stable protein
encapsulation and topical delivery into barrier-deficient skin.
en
dc.format.extent
14 Seiten
dc.rights.uri
http://creativecommons.org/licenses/by-nc/4.0/
dc.subject
thermoresponsive-nanogel
dc.subject
anti-inflammatory therapy
dc.subject
skin equivalents
dc.subject.ddc
500 Naturwissenschaften und Mathematik::540 Chemie
dc.subject.ddc
600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::615 Pharmakologie, Therapeutik
dc.title
Breaking the Barrier - Potent Anti-Inflammatory Activity following Efficient
Topical Delivery of Etanercept using Thermoresponsive Nanogels
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation
Theranostics 2018: 8(2):450-463
dcterms.bibliographicCitation.doi
10.7150/thno.21668
dcterms.bibliographicCitation.url
http://www.thno.org/v08p0450.htm
refubium.affiliation
Biologie, Chemie, Pharmazie
de
refubium.affiliation.other
Institut für Chemie und Biochemie
refubium.affiliation.other
Institut für Pharmazie
refubium.funding
Deutsche Forschungsgemeinschaft (DFG)
refubium.mycore.fudocsId
FUDOCS_document_000000028533
refubium.note.author
Gefördert durch die DFG und den Open-Access-Publikationsfonds der Freien
Universität Berlin.
refubium.resourceType.isindependentpub
no
refubium.mycore.derivateId
FUDOCS_derivate_000000009153
dcterms.accessRights.openaire
open access