39 research outputs found
Dermal Delivery of the High-Molecular-Weight Drug Tacrolimus by Means of Polyglycerol-Based Nanogels
Polyglycerol-based thermoresponsive nanogels (tNGs) have been shown to have excellent skin hydration properties and to be valuable delivery systems for sustained release of drugs into skin. In this study, we compared the skin penetration of tacrolimus formulated in tNGs with a commercial 0.1% tacrolimus ointment. The penetration of the drug was investigated in ex vivo abdominal and breast skin, while different methods for skin barrier disruption were investigated to improve skin permeability or simulate inflammatory conditions with compromised skin barrier. The amount of penetrated tacrolimus was measured in skin extracts by liquid chromatography tandem-mass spectrometry (LC-MS/MS), whereas the inflammatory markers IL-6 and IL-8 were detected by enzyme-linked immunosorbent assay (ELISA). Higher amounts of tacrolimus penetrated in breast as compared to abdominal skin or in barrier-disrupted as compared to intact skin, confirming that the stratum corneum is the main barrier for tacrolimus skin penetration. The anti-proliferative effect of the penetrated drug was measured in skin tissue/Jurkat cells co-cultures. Interestingly, tNGs exhibited similar anti-proliferative effects as the 0.1% tacrolimus ointment. We conclude that polyglycerol-based nanogels represent an interesting alternative to paraffin-based formulations for the treatment of inflammatory skin conditions
Fabrication of thermoresponsive nanogels by thermo-nanoprecipitation and in situ encapsulation of bioactives
A synthetic method for thermoresponsive, glycerol based nanogels has been
developed. The nanogels were synthesized by nanoprecipitation of the
orthogonally functionalized macromonomers and their gelation in water. The
crosslinking points were generated by strain promoted azide–alkyne
cycloaddition which enabled the in situ encapsulation of Doxorubicin HCl. The
mild and surfactant free reaction conditions make these nanogels ideal
candidates for biomedical applications
Breaking the Barrier - Potent Anti-Inflammatory Activity following Efficient Topical Delivery of Etanercept using Thermoresponsive Nanogels
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
Enhanced topical delivery of dexamethasone by β-cyclodextrin decorated thermoresponsive nanogels
Highly hydrophilic, responsive nanogels are attractive as potential systems for the topical delivery of bioactives encapsulated in their three-dimensional polymeric scaffold. Yet, these drug carrier systems suffer from drawbacks for efficient delivery of hydrophobic drugs. Addressing this, β-cyclodextrin (βCD) could be successfully introduced into the drug carrier systems by exploiting its unique affinity toward dexamethasone (DXM) as well as its role as topical penetration enhancer. The properties of βCD could be combined with those of thermoresponsive nanogels (tNGs) based on dendritic polyglycerol (dPG) as a crosslinker and linear thermoresponsive polyglycerol (tPG) inducing responsiveness to temperature changes. Electron paramagnetic resonance (EPR) studies localized the drug within the hydrophobic cavity of βCD by differences in its mobility and environmental polarity. In fact, the fabricated carriers combining a particulate delivery system with a conventional penetration enhancer, resulted in an efficient delivery of DXM to the epidermis and the dermis of human skin ex vivo (enhancement compared to commercial DXM cream: ∼2.5 fold in epidermis, ∼30 fold in dermis). Furthermore, DXM encapsulated in βCD tNGs applied to skin equivalents downregulated the expression of proinflammatory thymic stromal lymphopoietin (TSLP) and outperformed a commercially available DXM cream
GM 2-4 - a signpost for low and intermediate mass star formation
We present a multi-wavelength study of the region towards the GM 2-4 nebula
and the nearby source IRAS 05373+2340. Our near-infrared H2 1-0 S(1) line
observations reveal various shock-excited features which are part of several
bipolar outflows. We identify candidates for the driving sources of the
outflows from a comparison of the multi-waveband archival data-sets and SED
modelling. The SED spectral slope (\alpha(IRAC)) for all the protostars in the
field was then compared with the visual extinction map. This comparison
suggests that star formation is progressing from NE to SW across this region
Entwicklung und Anpassung thermoresponsiver Nanogele zur Behandlung entzündlicher Hautkrankheiten
This work presents the potential of polymeric nanoscale transporter systems
for the cutaneous delivery of drugs. Based on their unique physico-chemical
properties, tNGs were investigated for their ability to deliver therapeutic
moieties across the SC, while examining possible penetration pathways. This
work is presented in three sections focusing on novel synthetic strategies for
tNGs, a fundamental investigation of the interaction of tNGs with skin and
skin cells, and finally, their realization for the treatment of inflammatory
skin diseases.Mit dieser Arbeit wurde das Potential polymerer Nano-Transportsysteme für den
kutanen Transport von Wirkstoffen aufgezeigt. Basierend auf den einzigartigen
physikochemikalischen Eigenschaften wurden thermoresponsive Nanogele (tNGs)
auf ihre Fähigkeit hin getestet, Wirkstoffe über die stratum corneum (SC) zur
Epidermis und Dermis zu transportieren. Zudem wurden mögliche Penetrationswege
und -mechanismen der tNGs durch die Haut untersucht. Die Arbeit ist in drei
Kapitel unterteilt: Entwicklung und Evaluierung neuer Methoden für die
Nanogelsynthese, grundlegende Analyse von Wechselwirkung der tNGs mit Haut und
Hautzellen, und abschließend Evaluierung der therapeutischen Wirkung in
dermalen chronischen Entzündungskrankheiten
A Search for Embedded Young Stellar Objects in and near the IC 1396 Complex
The IRAS data base is used to locate young stellar object candidates in and near the IC 1396 complex located in the Cepheus OB2 association. Co-added survey data are used to identify all sources with a flux density Snu(100) greater than 10 Jy and with Snu(100) greater than Snu(60). The 15 sources located at the positions of globules and dark clouds are further analyzed using the in-scan slices to assess the source profile
Safety of tattoos and permanent make-up: a regulatory view
The continuous increase in the popularity of tattoos and permanent make-up (PMU) has led to substantial changes in their societal perception. Besides a better understanding of pathological conditions associated with the injection of highly diverse substances into subepidermal layers of the skin, their regulation has occupied regulatory bodies around the globe. In that sense, current regulatory progress in the European Union is an exemplary initiative for improving the safety of tattooing. On one hand, the compilation of market surveillance data has provided knowledge on hazardous substances present in tattoo inks. On the other hand, clinical data gathered from patients enabled correlation of adverse reactions with certain substances. Nevertheless, the assessment of risks remains a challenge due to knowledge gaps on the biokinetics of highly complex inks and their degradation products. This review article examines the strategies for regulating substances in tattoo inks and PMU in light of their potential future restriction in the frame of the REACH regulation. Substance categories are discussed in terms of their risk assessment and proposed concentration limits
Galvanic Replacement as a Synthetic Tool for the Construction of Anisotropic Magnetoplasmonic Nanocomposites with Synergistic Phototransducing and Magnetic Properties
Magnetoplasmonic nanomaterials, which combine light and magnetic field responsiveness in an advantageous manner, are attractive candidates for bio nanoapplications. However, the synthetic access to such hybrid particles has been limited by the incompatibility of the iron and gold based lattices. In this work, we provide the first insights into a new synthetic strategy for developing magnetoplasmonic anisotropic nanocomposites with prominent phototransducing properties. In our approach, magnetic nanocubes based on an alloy of iron oxide, zinc, and silver were constructed. In a key second stage, the galvanic replacement of silver with gold atoms yielded satellite like magnetoplasmonic anisotropic structures. Superior magnetic and photoconverting properties were observed for the novel magnetoplasmonic nanocomposites when compared with the pure parent structures. Moreover, the synergy between the magnetic and optical stimuli was examined, showing shape dependent contributions in the magnetization experiments. More importantly, an excellent cell ablation capability upon laser irradiation was observed for the magnetoplasmonic nanocomposites compared to the pure magnetic or plasmonic controls. Further demonstration of these novel theragnostic agents as MRI contrast agents is also reported even during the light irradiation event. Thus, the described particles showed promising properties for bioapplications emerging from the novel synthetic methodolog
Specific uptake mechanisms of well-tolerated thermoresponsive polyglycerol-based nanogels in antigen-presenting cells of the skin
Engineered nanogels are of high value for a targeted and controlled transport of compounds due to the ability to change their chemical properties by external stimuli. As it has been indicated that nanogels possess a high ability to penetrate the stratum corneum, it cannot be excluded that nanogels interact with dermal dendritic cells, especially in diseased skin. In this study the potential crosstalk of the thermoresponsive nanogels (tNGs) with the dendritic cells of the skin was investigated with the aim to determine the immunotoxicological properties of the nanogels. The investigated tNGs were made of dendritic polyglycerol (dPG) and poly(glycidyl methyl ether-co-ethyl glycidyl ether) (p(GME-co-EGE)), as polymer conferring thermoresponsive properties. Although the tNGs were taken up, they displayed neither cytotoxic and genotoxic effects nor any induction of reactive oxygen species in the tested cells. Interestingly, specific uptake mechanisms of the tNGs by the dendritic cells were depending on the nanogels cloud point temperature (Tcp), which determines the phase transition of the nanoparticle. The study points to caveolae-mediated endocytosis as being the major tNGs uptake mechanism at 37 °C, which is above the Tcp of the tNGs. Remarkably, an additional uptake mechanism, beside caveolae-mediated endocytosis, was observed at 29 °C, which is the Tcp of the tNGs. At this temperature, which is characterized by two different states of the tNGs, macropinocytosis was involved as well. In summary, our study highlights the impact of thermoresponsivity on the cellular uptake mechanisms which has to be taken into account if the tNGs are used as a drug delivery system