Correlation between the chemical composition of thermoresponsive nanogels and their interaction with the skin barrier

Giulbudagian, Michael; Rancan, Fiorenza; Klossek, A.; Yamamoto, Kenji; Jurisch, Jana; Neto, Victor Colombo; Schrade, Petra; Bachmann, S.; Rühl, E.; Blume-Peytavi, Ulrike; Vogt, Annika; Calderón, Marcelo

doi:10.1016/j.jconrel.2016.10.022

Cited by 43 publications

(48 citation statements)

References 45 publications

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“…In a previous study, ultrastructural analyses of the SCs of skin biopsies following 2 h tNG_tPG exposure revealed clear disordering and/or swelling within the comprising structural components, as well as apparent dilations of the spaces between these. 54 This was strongly suggestive of an enhanced state of hydration within the SC. 55 It was also demonstrated that lipid to protein ratios found within the SC were increased following application of tNG_tPG and, to a lesser extent, tNG_pNIPAM.…”

Section: Resultsmentioning

confidence: 93%

“…This may again relate to altered water contents within the skin equivalents, structural changes induced by tNGs, or occlusive effects induced by tNG presence on the equivalent's surface. 54 Nevertheless, the impact of ETR is clear, wherein its delivery by the tNGs correlated with the strongest and most consistent anti-inflammatory effects on the skin equivalents as is particularly notable in TSLP levels. Moreover, delivery of ETR in PBS results in less pronounced effects than applications of PBS alone, perhaps owing to the higher osmotic potential of the equivalents surface when proteins are applied.…”

Section: Resultsmentioning

confidence: 97%

“…It is however notable that the tNG tested here and elsewhere appear to show an innate ability to penetrate into the SC, or to interfere with its structural ordering, and that release from within the SC could significantly improve the penetration of proteins. 54 Future exploration of factors such as cross-linking density, rigidity, charge and hydrophilicity may prove insightful with regard to the SC penetrating properties of tNGs. 54 , 56 , 57 …”

Section: Resultsmentioning

confidence: 99%

“… 54 Future exploration of factors such as cross-linking density, rigidity, charge and hydrophilicity may prove insightful with regard to the SC penetrating properties of tNGs. 54 , 56 , 57 …”

Section: Resultsmentioning

confidence: 99%

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Breaking the Barrier - Potent Anti-Inflammatory Activity following Efficient Topical Delivery of Etanercept using Thermoresponsive Nanogels

et al. 2018

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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; ELISAResults: 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.

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Section: Resultsmentioning

confidence: 93%

Section: Resultsmentioning

confidence: 97%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Breaking the Barrier - Potent Anti-Inflammatory Activity following Efficient Topical Delivery of Etanercept using Thermoresponsive Nanogels

et al. 2018

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“…Larger studies on the penetration of micro‐ and nanoparticles have demonstrated that microparticles largely remain on the skin surface, but also reach the deeper infundibulum of scalp HFs. Even nanoparticles only penetrate at very limited rates depending on their physicochemical properties . Mild disturbance of the skin barrier can be associated with particle translocation into the viable tissue, cellular particle uptake and subsequent immune reactions .…”

Section: How Can Microbes Get Access To Keratinocytes and The Cutaneomentioning

confidence: 99%

The role of the microbiome in scalp hair follicle biology and disease

Polak-Witka

Rudnicka

Blume-Peytavi

et al. 2019

Experimental Dermatology

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The skin surface microbiome and its role in skin diseases have received increasing attention over the past years. Beyond, there is evidence for a continuous exchange with the cutaneous immune system in healthy skin, where hair follicles (HFs) provide unique anatomical niches. Especially, scalp HFs form large tubular invaginations, which extend deeply into the skin and harbour a variety of microorganisms. The distinct immunology of HFs with enhanced immune cell trafficking in superficial compartments in juxtaposition to immune‐privileged sites crucial for hair follicle cycling and regeneration makes this organ a highly susceptible structure. Depending on composition and penetration depth, microbiota may cause typical infections, but may also contribute to pro‐inflammatory environment in chronic inflammatory scalp diseases. Involvement in hair cycle regulation and immune cell maturation has been postulated. Herein, we review recent insights in hair follicle microbiome, immunology and penetration research and discuss clinical implications for scalp health and disease.

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Overcoming the Translational Gap – Nanotechnology in Dermal Drug Delivery

Zoschke¹,

Schäfer‐Korting²

2021

Fundamentals of Drug Delivery

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Correlation between the chemical composition of thermoresponsive nanogels and their interaction with the skin barrier

Cited by 43 publications

References 45 publications

Breaking the Barrier - Potent Anti-Inflammatory Activity following Efficient Topical Delivery of Etanercept using Thermoresponsive Nanogels

Breaking the Barrier - Potent Anti-Inflammatory Activity following Efficient Topical Delivery of Etanercept using Thermoresponsive Nanogels

The role of the microbiome in scalp hair follicle biology and disease

Overcoming the Translational Gap – Nanotechnology in Dermal Drug Delivery

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