Thermosensitive dendritic polyglycerol-based nanogels for cutaneous delivery of biomacromolecules

Witting, Madeleine; Molina, María; Obst, Katja; Plank, Roswitha; Eckl, Katja Martina; Hennies, Hans Christian; Calderón, Marcelo; Frieß, Wolfgang; Hedtrich, Sarah

doi:10.1016/j.nano.2015.02.017

Cited by 79 publications

(74 citation statements)

References 53 publications

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“…Thermoresponsive tNGs undergo conformational changes at temperatures around their T cp resulting in water loss and increase of hydrophobicity. In addition, the conformational change at temperatures close to T cp changes the loading capacity and leads to a thermal triggered compound release (Rancan et al, 2017;Witting et al, 2015). Since the T cp of the studied tNGs is close to the physiological skin temperature (32 C) the described tNGs are capable of releasing their payload into the viable part of the skin, before they are taken up by the non-targeted keratinocytes.…”

Section: Discussionmentioning

confidence: 96%

“…efficiently into the viable epidermis of human skin which is primarily composed of keratinocytes (Asadian-Birjand et al, 2012a;Samah et al, 2010;Witting et al, 2015). Potential interactions with keratinocytes of the viable epidermis cannot be entirely excluded, particularly in diseased and, hence, barrier impaired skin.…”

Section: Discussionmentioning

confidence: 99%

“…Of major interest for topical drug delivery are polymeric nanoparticles, nanoemulsions, lipid-based nanoparticles and dendrimers. Dendrimers composed of dendritic polyglycerol (dPG) are hyperbranched synthetic macromolecules that exhibit high-water solubility and biocompatibility (Goyal et al, 2016;Witting et al, 2015;Yang et al, 2012). Interestingly, dPG can serve as a macromolecular reagent to fabricate cross-linked hydrophilic three-dimensional polymeric networks referred to as nanogels (Asadian-Birjand et al, 2012aKabanov & Vinogradov, 2009).…”

Section: Introductionmentioning

confidence: 99%

“…These tNGs undergo a reversible phase-transition at the cloud point temperature (T cp ) of the polymer. They can be loaded with water-soluble or amphiphilic drugs, as well as biomacromolecules such as proteins, and have been shown to significantly increase drug penetration depth even of large molecules compared to conventional formulations (Witting et al, 2015). However, the loading content of dPG-based tNGs with highly hydrophobic drugs (e.g.…”

Section: Introductionmentioning

confidence: 99%

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Biocompatibility and characterization of polyglycerol-based thermoresponsive nanogels designed as novel drug-delivery systems and their intracellular localization in keratinocytes

et al. 2017

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(2017) Biocompatibility and characterization of polyglycerol-based thermoresponsive nanogels designed as novel drug-delivery systems and their intracellular localization in keratinocytes, Nanotoxicology, 11:2, 267-277, DOI: 10.1080/17435390.2017 ABSTRACTNovel nanogels that possess the capacity to change their physico-chemical properties in response to external stimuli are promising drug-delivery candidates for the treatment of severe skin diseases. As thermoresponsive nanogels (tNGs) are capable of enhancing penetration through biological barriers such as the stratum corneum and are taken up by keratinocytes of human skin, potential adverse consequences of their exposure must be elucidated. In this study, tNGs were synthesized from dendritic polyglycerol (dPG) and two thermoresponsive polymers. tNG_dPG_tPG are the combination of dPG with poly(glycidyl methyl ether-co-ethyl glycidyl ether) (p(GME-co-EGE)) and tNG_dPG_pNIPAM the one with poly(N-isopropylacrylamide) (pNIPAM). Both thermoresponsive nanogels are able to incorporate high amounts of dexamethasone and tacrolimus, drugs used in the treatment of severe skin diseases. Cellular uptake, intracellular localization and the toxicological properties of the tNGs were comprehensively characterized in primary normal human keratinocytes (NHK) and in spontaneously transformed aneuploid immortal keratinocyte cell line from adult human skin (HaCaT). Laser scanning confocal microscopy revealed fluorescently labeled tNGs entered into the cells and localized predominantly within lysosomal compartments. MTT assay, comet assay and carboxy-H2DCFDA assay, demonstrated neither cytotoxic or genotoxic effects, nor any induction of reactive oxygen species of the tNGs in keratinocytes. In addition, both tNGs were devoid of eye irritation potential as shown by bovine corneal opacity and permeability (BCOP) test and red blood cell (RBC) hemolysis assay. Therefore, our study provides evidence that tNGs are locally well tolerated and underlines their potential for cutaneous drug delivery. ARTICLE HISTORY

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Biocompatibility and characterization of polyglycerol-based thermoresponsive nanogels designed as novel drug-delivery systems and their intracellular localization in keratinocytes

et al. 2017

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“…In any case, after its application into the skin, NMs non-internalized transdermally are mainly released to wastewaters by two routes: attached to clothes in direct contact with the skin and washed away by water when washing or bathing. It has been demonstrated that an important fraction that ranges usually from 95 to >99% for non-targeted NMs to about 75-80% in surface-modified nanoparticles reaches the environment [123][124][125].…”

Section: Nanomaterials Administered Intentionally For Diagnostics or mentioning

confidence: 99%

Nanomaterials Release from Nano-Enabled Products

Vílchez

Fernández-Rosas

González-Gálvez

et al. 2015

The Handbook of Environmental Chemistry

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Nanomaterials release quantification and characterization is crucial for risk assessment studies, and experimental simulation studies provide the most concrete basis for estimating the release of nanomaterials in any stage of its life cycle. Nanomaterials are used in a broad range of applications, in different forms (embedded, as coatings, suspended, etc.) and with different size ranges. With all these variables, the number of scenarios where release of nanomaterials could occur is huge. In this chapter, we aim to review use-phase release scenarios that are usually considered in the literature, as well as the results of such studies and the protocols used for product ageing and for nanomaterial quantification and characterization. Finally, we point out the gaps in nanomaterials release studies and identify future research needs.

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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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Thermosensitive dendritic polyglycerol-based nanogels for cutaneous delivery of biomacromolecules

Cited by 79 publications

References 53 publications

Biocompatibility and characterization of polyglycerol-based thermoresponsive nanogels designed as novel drug-delivery systems and their intracellular localization in keratinocytes

Biocompatibility and characterization of polyglycerol-based thermoresponsive nanogels designed as novel drug-delivery systems and their intracellular localization in keratinocytes

Nanomaterials Release from Nano-Enabled Products

Overcoming the Translational Gap – Nanotechnology in Dermal Drug Delivery

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