Oxidation-Sensitive Core–Multishell Nanocarriers for the Controlled Delivery of Hydrophobic Drugs

Rajes, Keerthana; Walker, Karolina A; Hadam, Sabrina; Zabihi, Fatemeh; Ibrahim-Bacha, Jumana; Germer, Gregor; Patoka, Piotr; Wassermann, B.; Rancan, Fiorenza; Rühl, E.; Vogt, Annika; Haag, Rainer

doi:10.1021/acsbiomaterials.0c01771

Cited by 15 publications

(15 citation statements)

References 54 publications

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“…As the amount of naturally dissolvable NR is negligible, 1% is essentially the amount of encapsulated NR. A drug concentration of 1 wt% was found in all NR-loaded CMS nanocarriers, which correlates with the drug loading of nanocarriers with similar structures [ 42 , 43 ].…”

Section: Resultsmentioning

confidence: 99%

Novel Adhesive Nanocarriers Based on Mussel-Inspired Polyglycerols for the Application onto Mucosal Tissues

et al. 2022

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A synthetic route for adhesive core-multishell (CMS) nanocarriers for application to the oral mucosa was established using mussel-inspired catechol moieties. The three CMS nanocarriers with 8%, 13%, and 20% catechol functionalization were evaluated for loading capacity using Nile red, showing an overall loading of 1 wt%. The ability of Nile red loaded and functionalized nanocarriers to bind to a moist mucosal surface was tested in two complementary adhesion assays under static and dynamic conditions using monolayers of differentiated gingival keratinocytes. Adhesion properties of functionalized nanocarriers were compared to the adhesion of the non-functionalized nanocarrier. In both assays, the CMS nanocarrier functionalized with 8% catechol exhibited the strongest adhesion compared to its catechol-free counterpart and the CMS nanocarriers functionalized with 13% and 20% catechol.

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Section: Resultsmentioning

confidence: 99%

Novel Adhesive Nanocarriers Based on Mussel-Inspired Polyglycerols for the Application onto Mucosal Tissues

et al. 2022

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“…The detailed synthesis of rsCMS and osCMS nanocarriers is reported in previous publications. 30 , 31 Briefly, the CMS nanocarriers investigated in this study were prepared as follows: The rsCMS0 was synthesized by oxidating mercaptoundecanoic acid to disulfanediyldiundecanoic acid. This was then reacted with methoxy poly (ethylene glycol) amine through peptide coupling.…”

Section: Methodsmentioning

confidence: 99%

“…The rsCMS nanocarriers were prepared by introducing disulfide groups in the inner shell, 30 while thioether groups were inserted to obtain the osCMS nanocarriers. 31 The rsCMS nanocarriers have been shown to release the loaded cargo upon partial degradation following the reaction of free thiol groups (like glutathione) with the disulfide groups. As for the osCMS nanocarriers, the incorporated thioethers can be oxidized to sulfoxide by ROS.…”

Section: Introductionmentioning

confidence: 99%

Topical Delivery of Rapamycin by Means of Microenvironment-Sensitive Core-Multi-Shell Nanocarriers: Assessment of Anti-Inflammatory Activity in an ex vivo Skin/T Cell Co-Culture Model

Rancan¹,

Guo²,

Rajes³

et al. 2021

IJN

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Introduction Rapamycin (Rapa) is an immunosuppressive macrolide that inhibits the mechanistic target of rapamycin (mTOR) activity. Thanks to its anti-proliferative effects towards different cell types, including keratinocytes and T cells, Rapa shows promise in the treatment of skin diseases characterized by cell hyperproliferation. However, Rapa skin penetration is limited due to its lipophilic nature (log P = 4.3) and high molecular weight (MW = 914 g/mol). In previous studies, new microenvironment-sensitive core multishell (CMS) nanocarriers capable of sensing the redox state of inflamed skin were developed as more efficient and selective vehicles for macrolide delivery to inflamed skin. Methods In this study, we tested such redox-sensitive CMS nanocarriers using an inflammatory skin model based on human skin explants co-cultured with Jurkat T cells. Serine protease (SP) was applied on skin surface to induce skin barrier impairment and oxidative stress, whereas phytohaemagglutinin (PHA), IL-17A, and IL-22 were used to activate Jurkat cells. Activation markers, such as CD45 and CD69, phosphorylated ribosomal protein S6 (pRP-S6), and IL-2 release were monitored in activated T cells, whereas pro-inflammatory cytokines were measured in skin extracts and culture medium. Results We found that alteration of skin barrier proteins corneodesmosin (CDSN), occludin (Occl), and zonula occludens-1 (ZO-1) as well as oxidation-induced decrease of free thiol groups occurred upon SP-treatment. All Rapa formulations exerted inhibitory effects on T cells after penetration across ex vivo skin. No effects on skin inflammatory markers were detected. The superiority of the oxidative-sensitive CMS nanocarriers over the other formulations was observed with regard to drug delivery as well as downregulation of IL-2 release. Conclusion Overall, our results demonstrate that nanocarriers addressing features of diseased skin are promising approaches to improve the topical delivery of macrolide drugs.

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“…The spectral measurements of Leishmania brasiliensis promastigotes were carried out with a nanoIR2-s (Bruker (former Anasys), USA) photothermal expansion-based microscope combining atomic force microscopy with a local thermal expansion effect 28,29 . A schematic The projection shown in Fig.…”

Section: Compressed Afm-ir Spectral Imagingmentioning

confidence: 99%

Compressed AFM-IR hyperspectral nanoimaging of single Leishmania parasites

Hornemann¹,

Marschall²,

Metzner³

et al. 2022

Preprint

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Infrared hyperspectral imaging is a powerful approach in the field of materials and life sciences. However, the extension to modern sub-diffraction nanoimaging still remains a highly inefficient technique, as it acquires data via inherent sequential schemes. Here, we introduce the mathematical technique of low-rank matrix reconstruction to the sub-diffraction scheme of atomic force microscopy-based infrared spectroscopy (AFM-IR), for efficient hyperspectral infrared nanoimaging. To demonstrate its application potential, we chose the trypanosomatid unicellular parasites Leishmania species as a realistic target of biological importance. The mid-infrared spectral fingerprint window covering the spectral range from 1300 to 1900 cm −1 was chosen and a step width of 220 nm was applied for nanoimaging of single parasites. Multivariate statistics approaches such as hierarchical cluster analysis (HCA) were used for extracting the chemically distinct spatial locations. Subsequently, we randomly selected only 5 % from an originally gathered data cube of 134 (x) × 50 (y) × 148 (spectral) AFM-IR measurements and reconstructed the full data set by low-rank matrix recovery. The technique is evaluated by showing agreement in the cluster regions between full and reconstructed data cubes. We conclude that the corresponding measurement time of more than 14 hours can be reduced to less than 1 hour. These findings can significantly boost the practical applicability of hyperspectral nanoimaging in both academic and industrial settings involving nano-and bio-materials.

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Oxidation-Sensitive Core–Multishell Nanocarriers for the Controlled Delivery of Hydrophobic Drugs

Cited by 15 publications

References 54 publications

Novel Adhesive Nanocarriers Based on Mussel-Inspired Polyglycerols for the Application onto Mucosal Tissues

Novel Adhesive Nanocarriers Based on Mussel-Inspired Polyglycerols for the Application onto Mucosal Tissues

Topical Delivery of Rapamycin by Means of Microenvironment-Sensitive Core-Multi-Shell Nanocarriers: Assessment of Anti-Inflammatory Activity in an ex vivo Skin/T Cell Co-Culture Model

Compressed AFM-IR hyperspectral nanoimaging of single Leishmania parasites

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