Topically applied virus-like particles containing HIV-1 Pr55gag protein reach skin antigen-presenting cells after mild skin barrier disruption

Rancan, Fiorenza; Afraz, Zahra; Hadam, Sabrina; Weiss, Lina; Perrin, Hélène; Kliche, Alexander; Schrade, Petra; Bachmann, S.; Schäfer‐Korting, Monika; Blume-Peytavi, Ulrike; Wagner, Ralf; Combadière, Béhazine; Vogt, Annika

doi:10.1016/j.jconrel.2017.10.033

Cited by 7 publications

(6 citation statements)

References 48 publications

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“…The highest concentrations were found for IL-6, IL-8, and IL-1α, followed by IL-10. Similar results were obtained previously for intact as well as ex vivo wounds after short culture in the trans-well set-up [ 31 , 69 ]. Lower but constantly increasing concentrations were detected for IL-1β, IL-7, and TNF-α.…”

Section: Discussionsupporting

confidence: 90%

Effects of Adipose-Derived Stem Cells and Their Conditioned Medium in a Human Ex Vivo Wound Model

Guo

Schaudinn

Blume-Peytavi

et al. 2022

Cells

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Adult stem cells have been extensively investigated for tissue repair therapies. Adipose-derived stem cells (ASCs) were shown to improve wound healing by promoting re-epithelialization and vascularization as well as modulating the inflammatory immune response. In this study, we used ex vivo human skin cultured in a six-well plate with trans-well inserts as a model for superficial wounds. Standardized wounds were created and treated with allogeneic ASCs, ASCs conditioned medium (ASC-CM), or cell culture medium (DMEM) supplemented with fetal calf serum (FCS). Skin viability (XTT test), histology (hematoxylin and eosin, H and E), β-catenin expression as well as inflammatory mediators and growth factors were monitored over 12 days of skin culture. We observed only a moderate time-dependent decrease in skin metabolic activity while skin morphology was preserved, and re-epithelialization occurred at the wound edges. An increase in β-catenin expression was observed in the newly formed epithelia, especially in the samples treated with ASC-CM. In general, increased growth factors and inflammatory mediators, e.g., hepatocytes growth factor (HGF), platelet-derived growth factor subunit AA (PDGF-AA), IL-1α, IL-7, TNF-α, and IL-10, were observed over the incubation time. Interestingly, different expression profiles were observed for the different treatments. Samples treated with ASC-CM significantly increased the levels of inflammatory cytokines and PDGF-AA with respect to control, whereas the treatment with ASCs in DMEM with 10% FCS resulted in significantly increased levels of fibroblast growth factor-basic (FGF-basic) and moderate increases of immunomodulatory cytokines. These results confirm that the wound microenvironment can influence the type of mediators secreted by ASCs and the mode as to how they improve the wound healing process. Comparative investigations with pre-activated ASCs will elucidate further aspects of the wound healing mechanism and improve the protocols of ACS application.

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Section: Discussionsupporting

confidence: 90%

Effects of Adipose-Derived Stem Cells and Their Conditioned Medium in a Human Ex Vivo Wound Model

Guo

Schaudinn

Blume-Peytavi

et al. 2022

Cells

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“…These inflammatory mediators, which play a major role in skin inflammatory conditions like psoriasis, 66 , 67 are also considered as markers for skin irritation. 68 In cultured ex vivo human skin, these cytokines are expressed at low levels, 69 , 70 but their release can be boosted by various stimuli like barrier disruption 65 , 69 or stimulation of the protease-activated receptors 2 (PAR-2) signaling pathway. 34–36 In the investigated samples, the expression of pro-inflammatory markers varied widely among the donors, possibly as a result of inter-individual variability but also of different baseline levels of inflammatory cytokines depending on anatomic region (breast vs abdomen), type and extent of surgery, as well as transportation time.…”

Section: Resultsmentioning

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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“…Therefore, we selected this surfactant formulation to investigate the extent of PLGA particle uptake by skin cells once applied to the wound tissue. For this purpose, we used a short-term organ culture set-up that allowed keeping skin at the air–liquid interface and maintaining cell viability as well as their endocytic capacity [ 42 ]. Figure 3 a shows a schematic representation of the used transwell set-up.…”

Section: Resultsmentioning

confidence: 99%

Screening of Surfactants for Improved Delivery of Antimicrobials and Poly-Lactic-co-Glycolic Acid Particles in Wound Tissue

Rancan

Jurisch

Günday³

et al. 2021

Pharmaceutics

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Topical wound management is often a challenge due to the poor penetration of antimicrobials in wound tissue and across the biofilm matrix where bacteria are embedded. Surfactants have been used for decades to improve the stability of formulations, increase drug solubility, and enhance penetration. In this study, we screened different detergents with respect to their cytotoxicity and their ability to improve the penetration of poly-lactic-co-glycolic acid (PLGA) particles in wound tissue. Among the tested surfactants, Kolliphor SLS and Tween 80 increased the penetration of PLGA particles and had a limited cytotoxicity. Then, these surfactants were used to formulate PLGA particles loaded with the poorly water-soluble antibiotic ciprofloxacin. The antimicrobial efficacy of the formulations was tested in a wound infection model based on human ex vivo skin. We found that even though PLGA particles had the same antimicrobial efficiency than the particle-free drug formulation, thanks to their solubilizing and anti-biofilm properties, the surfactants remarkably improved the antimicrobial activity of ciprofloxacin with respect to the drug formulation in water. We conclude that the use of Tween 80 in antimicrobial formulations might be a safe and efficient option to improve the topical antimicrobial management of chronic wound infections.

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Topically applied virus-like particles containing HIV-1 Pr55gag protein reach skin antigen-presenting cells after mild skin barrier disruption

Cited by 7 publications

References 48 publications

Effects of Adipose-Derived Stem Cells and Their Conditioned Medium in a Human Ex Vivo Wound Model

Effects of Adipose-Derived Stem Cells and Their Conditioned Medium in a Human Ex Vivo Wound Model

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

Screening of Surfactants for Improved Delivery of Antimicrobials and Poly-Lactic-co-Glycolic Acid Particles in Wound Tissue

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