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Breaking the barrier
- 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; TNF alpha 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 stableTopical 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; TNF alpha 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-TNFa fusion protein etanercept (ETR) (similar to 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.…
Author details: | Michael GiulbudagianORCiDGND, Guy YeallandORCiD, Stefan HönzkeGND, Alexander EdlichGND, Birte Geisendörfer, Burkhard KleuserORCiDGND, Sarah HedtrichORCiD, Marcelo CalderónORCiD |
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URN: | urn:nbn:de:kobv:517-opus4-459301 |
DOI: | https://doi.org/10.25932/publishup-45930 |
ISSN: | 1866-8372 |
Title of parent work (German): | Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe |
Subtitle (English): | potent anti-inflammatory activity following efficient topical delivery of etanercept using thermoresponsive nanogels |
Publication series (Volume number): | Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe (1030) |
Publication type: | Postprint |
Language: | English |
Date of first publication: | 2020/12/14 |
Publication year: | 2018 |
Publishing institution: | Universität Potsdam |
Release date: | 2020/12/14 |
Tag: | anti-inflammatory therapy; etanercept; skin equivalents; thermoresponsive-nanogel; topical |
Issue: | 1030 |
Number of pages: | 16 |
First page: | 450 |
Last Page: | 463 |
Source: | Theranostics 8 (2018) 2, 450-463 DOI:10.7150/thno.21668 |
Organizational units: | Mathematisch-Naturwissenschaftliche Fakultät / Institut für Ernährungswissenschaft |
DDC classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Peer review: | Referiert |
Publishing method: | Open Access / Green Open-Access |
License (German): | CC-BY-NC-SA - Namensnennung, nicht kommerziell, Weitergabe zu gleichen Bedingungen 4.0 International |