Controlling protein interactions in blood for effective liver immunosuppressive therapy by silica nanocapsules

Jiang, Shuai; Prozeller, Domenik; Pereira, Jorge C.; Simon, Johanna; Han, Shen; Wirsching, Sebastian; Fichter, Michael; Mottola, Milagro; Lieberwirth, Ingo; Morsbach, Svenja; Mailänder, Volker; Gehring, Stephan; Crespy, Daniel; Landfester, Katharina

doi:10.1039/c9nr09879h

Cited by 29 publications

(16 citation statements)

References 87 publications

(120 reference statements)

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“…During an experimental study, these nanocapsules were internalized by non-parenchymal murine liver cells and resulted in suppression of inflammatory response of liver macrophages and a significant decrease in inflammatory cytokines. Pegylation of these nanocapsules led to good stability in plasma and controlled interaction with blood proteins[ 49 ].…”

Section: Transplant Recipientsmentioning

confidence: 99%

Current status of glucocorticoid usage in solid organ transplantation

Dashti‐Khavidaki¹,

Saidi²,

Lü³

2021

WJT

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Glucocorticoids (GCs) have been the mainstay of immunosuppressive therapy in solid organ transplantation (SOT) for decades, due to their potent effects on innate immunity and tissue protective effects. However, some SOT centers are reluctant to administer GCs long-term because of the various related side effects. This review summarizes the advantages and disadvantages of GCs in SOT. PubMed and Scopus databases were searched from 2011 to April 2021 using search syntaxes covering “transplantation” and “glucocorticoids”. GCs are used in transplant recipients, transplant donors, and organ perfusate solution to improve transplant outcomes. In SOT recipients, GCs are administered as induction and maintenance immunosuppressive therapy. GCs are also the cornerstone to treat acute antibody- and T-cell-mediated rejections. Addition of GCs to organ perfusate solution and pretreatment of transplant donors with GCs are recommended by some guidelines and protocols, to reduce ischemia-reperfusion injury peri-transplant. GCs with low bioavailability and high potency for GC receptors, such as budesonide, nanoparticle-mediated targeted delivery of GCs to specific organs, and combination use of dexamethasone with inducers of immune-regulatory cells, are new methods of GC application in SOT patients to reduce side effects or induce immune-tolerance instead of immunosuppression. Various side effects involving different non-targeted organs/tissues, such as bone, cardiovascular, neuromuscular, skin and gastrointestinal tract, have been noted for GCs. There are also potential drug-drug interactions for GCs in SOT patients.

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Section: Transplant Recipientsmentioning

confidence: 99%

Current status of glucocorticoid usage in solid organ transplantation

Dashti‐Khavidaki¹,

Saidi²,

Lü³

2021

WJT

View full text Add to dashboard Cite

show abstract

“…During an experimental study, these nanocapsules were internalized by non-parenchymal murine liver cells and resulted in suppression of inflammatory response of liver macrophages and significant decrease in inflammatory cytokines. Pegylation of these nanocapsules led to good stability in plasma and controlled interaction with blood proteins [49] .…”

Section: New Horizons Of Gcs Use In Sot Recipientsmentioning

confidence: 99%

Current Status of Glucocorticoid Usage in Solid Organ Transplantation

Dashti‐Khavidaki¹,

Saidi²,

Lü³

2021

Preprint

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Glucocorticoids (GCs) have been the mainstay of immunosuppressive therapy in solid organ transplantation (SOT) for decades due to their potent effects on the innate immunity and tissue protective effects. But, some SOT centers are reluctant to administer GCs for long-time due to the various side effects. This review summarizes advantages and disadvantages of GCs in SOT. PubMed and Scopus databases were searched from 2011 to April 2021 using search syntaxes cover “transplantation” and “glucocorticoids”.GCs are used in transplant recipients, transplant donors, and organ perfusate solution to improve transplant outcomes. In SOT recipients GCs are administered as induction and maintenance immunosuppressive therapy. GCs are also the cornerstone to treat acute anti-body- and T-cell-mediated rejections. Addition of GCs to organ perfusate solution and pretreatment of transplant donors with GCs are recommended by some guidelines and protocols to reduce ischemia-reperfusion injury peri-transplant. GCs with low bioavailability and high potency for GC receptors such as budesonide, nanoparticle-mediated targeted delivery of GCs to specific organs, and combination use of dexamethasone with inducers of immune-regulatory cells are new methods of GC usage in SOT patients to reduce side effects or induce immune-tolerance instead of immunosuppression. Various side effects on different non-targeted organs/tissues such as bone, cardiovascular, neuromuscular, skin, and gastrointestinal tract have been noted for GCs. There are also potential drug-drug interactions for GCs in SOT patients.

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“…Mesoporous silica nanoparticles (MSNs) have attracted great attention because of their special features such as their unique porous structure, large surface area, pore volume and strong absorbability [21][22][23][24][25]. All these features allow better control of drug loading and release.…”

Section: Introductionmentioning

confidence: 99%

Novel IMB16-4 Compound Loaded into Silica Nanoparticles Exhibits Enhanced Oral Bioavailability and Increased Anti-Liver Fibrosis In Vitro

Niu¹,

Wang²,

Niu³

et al. 2021

Molecules

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Background: Liver fibrosis, as a common and refractory disease, is challenging to treat due to the lack of effective agents worldwide. Recently, we have developed a novel compound, N-(3,4,5-trichlorophenyl)-2(3-nitrobenzenesulfonamide) benzamide (IMB16-4), which is expected to have good potential effects against liver fibrosis. However, IMB16-4 is water-insoluble and has very low bioavailability. Methods: Mesoporous silica nanoparticles (MSNs) were selected as drug carriers for the purpose of increasing the dissolution of IMB16-4, as well as improving its oral bioavailability and inhibiting liver fibrosis. The physical states of IMB16-4 and IMB16-4-MSNs were investigated using nitrogen adsorption, thermogravimetric analysis (TGA), HPLC, UV-Vis, X-ray diffraction (XRD) and differential scanning calorimetry (DSC). Results: The results show that MSNs enhanced the dissolution rate of IMB16-4 significantly. IMB16-4-MSNs reduced cytotoxicity at high concentrations of IMB16-4 on human hepatic stellate cells LX-2 cells and improved oral bioavailability up to 530% compared with raw IMB16-4 on Sprague–Dawley (SD) rats. In addition, IMB16-4-MSNs repressed hepatic fibrogenesis by decreasing the expression of hepatic fibrogenic markers, including α-smooth muscle actin (α-SMA), transforming growth factor-beta (TGF-β1) and matrix metalloproteinase-2 (MMP2) in LX-2 cells. Conclusions: These results provided powerful information on the use of IMB16-4-MSNs for the treatment of liver fibrosis in the future.

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Controlling protein interactions in blood for effective liver immunosuppressive therapy by silica nanocapsules

Abstract: Silica nanocapsules are engineered to display controlled blood protein interactions for liver immunosuppressive therapy.

Cited by 29 publications

References 87 publications

Current status of glucocorticoid usage in solid organ transplantation

Current status of glucocorticoid usage in solid organ transplantation

Current Status of Glucocorticoid Usage in Solid Organ Transplantation

Novel IMB16-4 Compound Loaded into Silica Nanoparticles Exhibits Enhanced Oral Bioavailability and Increased Anti-Liver Fibrosis In Vitro

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