In vivo delivery of a peptide, ghrelin antagonist, with mesoporous silicon microparticles

Kilpeläinen, M.; Riikonen, Joakim; Vlasova, Maria; Huotari, Anne; Lehto, Vesa‐Pekka; Salonen, Jarno; Herzig, Karl‐Heinz; Järvinen, Kristiina

doi:10.1016/j.jconrel.2009.03.017

Cited by 118 publications

(113 citation statements)

References 28 publications

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“…The preparation and physicochemical characterization of the PSi microparticles have been described in detail in the literature. 3,12,14,15,19,22 In this study, two microsized THCPSi fractions were prepared: 1Ϫ10 and 10Ϫ25 m. The average pore diameter of these particles was 9.8 nm. The specific surface area was 322 m 2 /g, and the pore volume was 0.81 cm 3 /g.…”

Section: Resultsmentioning

confidence: 99%

“…Microparticles did not induce changes in plasma cytokine concentrations after subcutaneous administration in rats. 19 By combining the advantageous properties of the PSi materials with those of nanoscaled vehicles, even greater benefits in the development of drug delivery carriers can be achieved. 8 It is known that silicon-based nanomaterials can degrade rapidly in vivo into orthosilicic acid and therefore be easily excreted from the animal body.…”

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confidence: 99%

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Biocompatibility of Thermally Hydrocarbonized Porous Silicon Nanoparticles and their Biodistribution in Rats

et al. 2010

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Porous silicon (PSi) particles have been studied for the effects they elicit in Caco-2 and RAW 264.7 macrophage cells in terms of toxicity, oxidative stress, and inflammatory response. The most suitable particles were then functionalized with a novel 18 F label to assess their biodistribution after enteral and parenteral administration in a rat model. The results show that thermally hydrocarbonized porous silicon (THCPSi) nanoparticles did not induce any significant toxicity, oxidative stress, or inflammatory response in Caco-2 and RAW 264.7 macrophage cells. Fluorescently labeled nanoparticles were associated with the cells surface but were not extensively internalized. Biodistribution studies in rats using novel 18 F-labeled THCPSi nanoparticles demonstrated that the particles passed intact through the gastrointestinal tract after oral administration and were also not absorbed from a subcutaneous deposit. After intravenous administration, the particles were found mainly in the liver and spleen, indicating rapid removal from the circulation. Overall, these silicon-based nanosystems exhibit excellent in vivo stability, low cytotoxicity, and nonimmunogenic profiles, ideal for oral drug delivery purposes.

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Section: Resultsmentioning

confidence: 99%

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confidence: 99%

Biocompatibility of Thermally Hydrocarbonized Porous Silicon Nanoparticles and their Biodistribution in Rats

et al. 2010

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“…PSi differs from many of the commonly used drug carriers since the loading of peptides is much easier compared with, for example, typically used polymer materials, and there is no need to use conditions that can be harmful for peptides such as strong solvents or high temperatures. Our research group demonstrated the promising features of PSi for sustained delivery of peptides (Kilpeläinen et al, 2009;Kovalainen et al, 2012;Huotari et al, 2013). In the following sections, we give an overview on the PSi material and its use in peptide delivery where the subcutaneous route has shown to be the preferable administration route.…”

Section: Porous Silicon As a Novel Materials For Peptide Deliverymentioning

confidence: 99%

Novel Delivery Systems for Improving the Clinical Use of Peptides

et al. 2015

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“…Mesoporous silica nanoparticles (MSNs) are a versatile nanocarrier format that has been used for the delivery of chemotherapeutic agents[5,6], oligonucleotides[7,8], and proteins[9–11]. MSNs feature a stable framework to load and shelter cargo from proteases and the immune system and combine high cellular uptake efficiency with flexible surface functionalisation.…”

Section: Introductionmentioning

confidence: 99%

Nanoparticle mediated delivery and small molecule triggered activation of proteins in the nucleus

Chiu

Bates

Helma

et al. 2018

Nucleus

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Protein transfection is a versatile tool to study or manipulate cellular processes and also shows great therapeutic potential. However, the repertoire of cost effective techniques for efficient and minimally cytotoxic delivery remains limited. Mesoporous silica nanoparticles (MSNs) are multifunctional nanocarriers for cellular delivery of a wide range of molecules, they are simple and economical to synthesize and have shown great promise for protein delivery. In this work we present a general strategy to optimize the delivery of active protein to the nucleus. We generated a bimolecular Venus based optical sensor that exclusively detects active and bioavailable protein for the performance of multi-parameter optimization of protein delivery. In conjunction with cell viability tests we maximized MSN protein delivery and biocompatibility and achieved highly efficient protein transfection rates of 80%. Using the sensor to measure live-cell protein delivery kinetics, we observed heterogeneous timings within cell populations which could have a confounding effect on function studies. To address this problem we fused a split or dimerization dependent protein of interest to chemically induced dimerization (CID) components, permitting control over its activity following cellular delivery. Using the split Venus protein we directly show that addition of a small molecule dimerizer causes synchronous activation of the delivered protein across the entire cell population. This combination of cellular delivery and triggered activation provides a defined starting point for functional studies and could be applied to other protein transfection methods.

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In vivo delivery of a peptide, ghrelin antagonist, with mesoporous silicon microparticles

Cited by 118 publications

References 28 publications

Biocompatibility of Thermally Hydrocarbonized Porous Silicon Nanoparticles and their Biodistribution in Rats

Biocompatibility of Thermally Hydrocarbonized Porous Silicon Nanoparticles and their Biodistribution in Rats

Novel Delivery Systems for Improving the Clinical Use of Peptides

Nanoparticle mediated delivery and small molecule triggered activation of proteins in the nucleus

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