Crosstalk between core-multishell nanocarriers for cutaneous drug delivery and antigen-presenting cells of the skin

Edlich, Alexander; Volz, Pierre; Brodwolf, Robert; Unbehauen, Michael; Mundhenk, Lars; Gruber, Achim D.; Hedtrich, Sarah; Haag, Rainer; Alexiev, Ulrike; Kleuser, Burkhard

doi:10.1016/j.biomaterials.2018.01.058

Cited by 11 publications

(5 citation statements)

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“…Similar intracellular pathways have been described reflecting processes also involved in autophagy (endosome/exosome secretory pathway) [36]. For the Langerhans cell line XS52, it has been shown that CMS nanocarrier is not taken up by one exclusive pathway, but by micropinocytosis, caveolaemediated endocytosis, and clathrin-mediated endocytosis [37]. In this study, a perinuclear localization of CMS 10-E-15-350 was determined by CLSM analyses.…”

Section: Discussionsupporting

confidence: 61%

Characterization of an ester-based core-multishell (CMS) nanocarrier for the topical application at the oral mucosa

et al. 2021

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Objectives Topical drug administration is commonly applied to control oral inflammation. However, it requires sufficient drug adherence and a high degree of bioavailability. Here, we tested the hypothesis whether an ester-based core-multishell (CMS) nanocarrier is a suitable nontoxic drug-delivery system that penetrates efficiently to oral mucosal tissues, and thereby, increase the bioavailability of topically applied drugs. Material and methods To evaluate adhesion and penetration, the fluorescence-labeled CMS 10-E-15-350 nanocarrier was applied to ex vivo porcine masticatory and lining mucosa in a Franz cell diffusion assay and to an in vitro 3D model. In gingival epithelial cells, potential cytotoxicity and proliferative effects of the nanocarrier were determined by MTT and sulphorhodamine B assays, respectively. Transepithelial electrical resistance (TEER) was measured in presence and absence of CMS 10-E-15-350 using an Endohm-12 chamber and a volt-ohm-meter. Cellular nanocarrier uptake was analyzed by laser scanning microscopy. Inflammatory responses were determined by monitoring pro-inflammatory cytokines using real-time PCR and ELISA. Results CMS nanocarrier adhered to mucosal tissues within 5 min in an in vitro model and in ex vivo porcine tissues. The CMS nanocarrier exhibited no cytotoxic effects and induced no inflammatory responses. Furthermore, the physical barrier expressed by the TEER remained unaffected by the nanocarrier. Conclusions CMS 10-E-15-350 adhered to the oral mucosa and adhesion increased over time which is a prerequisite for an efficient drug release. Since TEER is unaffected, CMS nanocarrier may enter the oral mucosa transcellularly. Clinical relevance Nanocarrier technology is a novel and innovative approach for efficient topical drug delivery at the oral mucosa.

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Section: Discussionsupporting

confidence: 61%

Characterization of an ester-based core-multishell (CMS) nanocarrier for the topical application at the oral mucosa

et al. 2021

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“…Data were reported as the means of two independent experiments (three replicates each) ± standard error of mean and were expressed as percent viability with respect to the control. SDS 0.0035% served as the positive control …”

Section: Methodsmentioning

confidence: 99%

“…Then, the medium was removed, and the cells were washed three times with ice-cold phosphate-buffered saline. The cells were harvested and analyzed on FACSCanto . The counted cells were selected on a forward/sideward scatter plot to exclude debris and dead cells.…”

Section: Methodsmentioning

confidence: 99%

“…SDS 0.0035% served as the positive control. 25 Reactive Oxygen Species Assay. The generation of ROS in normal human primary fibroblasts and keratinocytes was investigated with a CellROX oxidative stress reagent (Thermo Fisher Scientific).…”

Section: ■ Materials and Methodsmentioning

confidence: 99%

“…The cells were harvested and analyzed on FACSCanto. 25 The counted cells were selected on a forward/sideward scatter plot to exclude debris and dead cells. The fluorescence of CellROX Orange was determined in the PE-A channel.…”

Section: ■ Materials and Methodsmentioning

confidence: 99%

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Hydrogels Containing Budesonide-Loaded Nanoparticles to Facilitate Percutaneous Absorption for Atopic Dermatitis Treatment Applications

Campos

Proença

Costa

et al. 2021

ACS Appl. Polym. Mater.

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Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disorder characterized by intense itching and recurrent eczematous lesions. Topical corticosteroids are the firstline treatment to control moderate-to-severe AD; however, prolonged application of corticosteroids is required, which can result in dermal atrophy as a side effect. Drug-delivery systems can provide more effective and targeted therapy strategies. In this study, budesonide (BUD) was encapsulated into chitosan (CS)coated PLGA nanoparticles, which were further incorporated into poloxamer hydrogels to improve the anti-inflammatory activity and decrease adverse effects. The nanoparticles were prepared by the emulsification−solvent evaporation technique, and their physicochemical characteristics were evaluated. Rheological properties of the hydrogels, such as viscosity and sol−gel transition temperature, were evaluated with and without nanoparticles. In vitro release kinetics and ex vivo drug absorption studies were performed using Franz diffusion cells. The nanoparticles showed a mean diameter of 324 ± 4 nm, positive ζ potential (20 mV) due to CS coating, and high encapsulation efficiency (>90%). The nanoparticles did not show cytotoxic effects in primary human fibroblasts and keratinocytes; however, all formulations induced the generation of reactive oxygen species. Both nanoparticles and hydrogels were able to change the release kinetics of BUD when compared to the nonencapsulated compound. Nanoparticles were not able to surmount the stratum corneum of excised human skin, but the nanoencapsulation facilitated the skin absorption of BUD. The hydrogels containing nanoparticles or not showed non-Newtonian and pseudoplastic behavior. The nanoformulations seem to be a good candidate to deliver glucocorticoids in the skin of AD patients.

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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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Crosstalk between core-multishell nanocarriers for cutaneous drug delivery and antigen-presenting cells of the skin

Cited by 11 publications

References 74 publications

Characterization of an ester-based core-multishell (CMS) nanocarrier for the topical application at the oral mucosa

Characterization of an ester-based core-multishell (CMS) nanocarrier for the topical application at the oral mucosa

Hydrogels Containing Budesonide-Loaded Nanoparticles to Facilitate Percutaneous Absorption for Atopic Dermatitis Treatment Applications

Overcoming the Translational Gap – Nanotechnology in Dermal Drug Delivery

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