The Experts below are selected from a list of 39147 Experts worldwide ranked by ideXlab platform
Alyssa Panitch - One of the best experts on this subject based on the ideXlab platform.
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Thermoresponsive, hollow, degradable core-shell nanoparticles for intra-articular delivery of anti-Inflammatory Peptide.
Journal of controlled release : official journal of the Controlled Release Society, 2020Co-Authors: Marcus A Deloney, Kyra Smart, Blaine A. Christiansen, Alyssa PanitchAbstract:Abstract Inflammation following joint trauma contributes to cartilage degradation and progression of post traumatic osteoarthritis (PTOA). Therefore, drug delivery vehicles that deliver effective anti-Inflammatory treatments have the potential to prevent PTOA. We have developed solid and hollow, thermoresponsive nanoparticles for the controlled release of our anti-Inflammatory MK2-inhibiting (MK2i) Peptide for intra-articular injection to halt inflammation that contributes to the advancement of PTOA. This system exploits the thermosensitive characteristic of N-isopropyl acrylamide (NIPAm) to transition phases when passing through its lower critical solution temperature (LCST). The nanoparticles (NPs) swell below the LCST and constrict above it. Non-crosslinked poly(NIPAm) (pNIPAm), held above its LCST, formed hydrophobic cores around which shells composed of NIPAm, degradable crosslinker N, N′-bis (acryloyl) cystamine (BAC), sulfated 2-acrylamido-2-methyl-1-propanesulfonic acid (AMPS), and acrylic acid (AAc) were polymerized. Removal of the non-crosslinked pNIPAm cores via diffusion produced thermosensitive, degradable nanoparticles with low density, or hollow, cores. The data presented here revealed low-density, termed hollow, nanoparticles (hNPs) load and release significantly more MK2i than solid nanoparticles (sNPs). Furthermore, drug loading below the LCST of NIPAm results in roughly 2.5 times more therapeutic encapsulation compared to loading particles in their constricted state. Hollow nanoparticles increase drug loading compared to solid nanoparticles, are taken up into chondrocytes within 24 h, cleared from the cells within 6 days, significantly decrease the secretion of the proInflammatory cytokine IL-6, and, via intra-articular injection, are successfully delivered into the joint space of rats. The Peptide loaded nanoparticles provide a reproducible platform for intra-articular delivery of therapeutics.
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Collagen-binding nanoparticles for extracellular anti-Inflammatory Peptide delivery decrease platelet activation, promote endothelial migration, and suppress inflammation.
Acta biomaterialia, 2016Co-Authors: James Mcmasters, Alyssa PanitchAbstract:Abstract Peripheral artery disease is an atherosclerotic stenosis in the peripheral vasculature that is typically treated via percutaneous transluminal angioplasty. Deployment of the angioplasty balloon damages the endothelial layer, exposing the underlying collagen and allowing for the binding and activation of circulating platelets which initiate an Inflammatory cascade leading to eventual restenosis. Here, we report on collagen-binding sulfated poly(N-isopropylacrylamide) nanoparticles that are able to target to the denuded endothelium. Once bound, these nanoparticles present a barrier that reduces cellular and platelet adhesion to the collagenous surface by 67% in whole blood and 59% in platelet-rich plasma under biologically relevant shear rates. In vitro studies indicate that the collagen-binding nanoparticles are able to load and release therapeutic quantities of anti-Inflammatory Peptides, with the particles reducing inflammation in endothelial and smooth muscle cells by 30% and 40% respectively. Once bound to collagen, the nanoparticles increased endothelial migration while avoiding uptake by smooth muscle cells, indicating that they may promote regeneration of the damaged endothelium while remaining anchored to the collagenous matrix and locally releasing anti-Inflammatory Peptides into the injured area. Combined, these collagen-binding nanoparticles have the potential to reduce inflammation, and the subsequent restenosis, while simultaneously promoting endothelial regeneration following balloon angioplasty. Statement of Significance In this manuscript, we present our work on the development and characterization of a novel temperature sensitive collagen-binding nanoparticle system. We demonstrate that when bound to a collagenous matrix, the nanoparticles are able to promote endothelial migration while avoiding cellular uptake. We also show that the nanoparticles are able to reduce inflammation via the release of anti-Inflammatory Peptides which, when combined with its ability to inhibit platelet binding, could lead to reduced intimal hyperplasia following balloon angioplasty. The drug delivery platform presented represents a unique dual therapy biomaterial wherein the nanoparticle itself plays a crucial role in the system’s overall therapeutic potential while simultaneously releasing anti-Inflammatory Peptides.
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Controlled release of anti-Inflammatory Peptides from reducible thermosensitive nanoparticles suppresses cartilage inflammation.
Nanomedicine : nanotechnology biology and medicine, 2016Co-Authors: Jenny B. Lin, Scott Poh, Alyssa PanitchAbstract:Characterized by pain, cartilage degradation, and inflammation, osteoarthritis is often treated with anti-Inflammatory therapies that provide short-term relief but can have adverse side effects; intra-articular drug delivery systems with controlled release of anti-Inflammatory Peptides using degradable poly(N-isopropylacrylamide) (pNIPAM) nanoparticles could prolong relief and minimize these side effects. Nanoparticles provide a biocompatible drug carrier that can protect encapsulated therapeutics from enzymatic degradation and increase payload delivery upon encountering a degradation stimulus. Here we demonstrate passive targeting of inflamed cartilage ex vivo by uptake of PEGylated pNIPAM nanoparticles with degradable disulfide crosslinks (abbreviated as NGPEGSS) into chondrocytes and subsequent intracellular release of an anti-Inflammatory Peptide KAFAKLAARLYRKALARQLGVAA (KAFAK). The KAFAK-loaded NGPEGSS treatment reduced ex vivo inflammation to a greater extent compared to its non-degradable counterparts. This study highlights a nanoparticle system that delivers therapeutics intracellularly with improved efficacy by triggered degradation and suppresses inflammation in multiple cell types within an inflamed joint.
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Release of Anti-Inflammatory Peptides from Thermosensitive Nanoparticles with Degradable Cross-Links Suppresses Pro-Inflammatory Cytokine Production
Biomacromolecules, 2015Co-Authors: Scott Poh, Jenny B. Lin, Alyssa PanitchAbstract:Pro-Inflammatory cytokines tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) are mediators in the development of many Inflammatory diseases. To demonstrate that macrophages take up and respond to thermosensitive nanoparticle drug carriers, we synthesized PEGylated poly(N-isopropylacrylamide-2-acrylamido-2-methyl-1-propanesulfonate) particles cross-linked with degradable disulfide (N,N′-bis(acryloyl)cystamine) (NGPEGSS). An anti-Inflammatory Peptide (KAFAK) was loaded and released from the thermosensitive nanoparticles and shown to suppress levels of TNF-α and IL-6 production in macrophages. Cellular uptake of fluorescent, thermosensitive, and degradable nanoparticles and therapeutic efficacy of free KAFAK Peptide compared to that of KAFAK loaded in PEGylated degradable thermosensitive nanoparticles were examined. The data suggests that the degradable, thermosensitive nanoparticles loaded with KAFAK may be an effective tool to treat Inflammatory diseases.
Artur Schmidtchen - One of the best experts on this subject based on the ideXlab platform.
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pseudomonas aeruginosa elastase cleaves a c terminal Peptide from human thrombin that inhibits host Inflammatory responses
Nature Communications, 2016Co-Authors: Mariena J A Van Der Plas, Ravi K V Bhongir, Sven Kjellstrom, Helena Siller, Gopinath Kasetty, Matthias Morgelin, Artur SchmidtchenAbstract:Pseudomonas aeruginosa is an opportunistic pathogen known for its immune evasive abilities amongst others by degradation of a large variety of host proteins. Here we show that digestion of thrombin by P. aeruginosa elastase leads to the release of the C-terminal thrombin-derived Peptide FYT21, which inhibits pro-Inflammatory responses to several pathogen-associated molecular patterns in vitro and in vivo by preventing toll-like receptor dimerization and subsequent activation of down-stream signalling pathways. Thus, P. aeruginosa 'hijacks' an endogenous anti-Inflammatory Peptide-based mechanism, thereby enabling modulation and circumvention of host responses.
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Effects of PEGylation on Membrane and Lipopolysaccharide Interactions of Host Defense Peptides
Biomacromolecules, 2014Co-Authors: Shalini Singh, Matthias Morgelin, Artur Schmidtchen, Praveen Papareddy, Martin MalmstenAbstract:Effects of poly(ethylene glycol) (PEG) conjugation on Peptide interactions with lipid membranes and lipopolysaccharide (LPS) were investigated for KYE28 (KYEITTIHNLFRKLTHRLFRRNFGYTLR), an antimicrobial and anti-Inflammatory Peptide derived from human heparin cofactor II. In particular, effects of PEG length and localization was investigated by ellipsometry, circular dichroism, nanoparticle tracking analysis, and fluorescence/electron microscopy. PEGylation of KYE28 reduces Peptide binding to lipid membranes, an effect accentuated at increasing PEG length, but less sensitive to conjugation site. The reduced binding causes suppressed liposome leakage induction, as well as bacterial lysis. As a result of this, the antimicrobial effects of KYE28 is partially lost with increasing PEG length, but hemolysis also strongly suppressed and selecticity improved. Through this, conditions can be found, at which the PEGylated Peptide displays simultaneously efficient antimicrobial affects and low hemolysis in blood. Importantly, PEGylation does not markedly affect the anti-Inflammatory effects of KYE28. The combination of reduced toxicity, increased selectivity, and retained anti-Inflammatory effect after PEGylation, as well as reduced scavenging by serum proteins, thus shows that PEG conjugation may offer opportunities in the development of effective and selective anti-Inflammatory Peptides.
Young-sook Cho - One of the best experts on this subject based on the ideXlab platform.
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Purification and anti-Inflammatory action of triPeptide from salmon pectoral fin byproduct protein hydrolysate
Food chemistry, 2014Co-Authors: Chang-bum Ahn, Young-sook ChoAbstract:Abstract In this study, the anti-Inflammatory Peptide from salmon pectoral fin byproduct protein hydrolysate by pepsin hydrolysis, was purified and identified using Sephadex G-25 gel permeation chromatography, high performance liquid chromatography and time-of-flight liquid chromatography/tandem mass spectrometry (TOF LC/MS/MS). The purified anti-Inflammatory Peptide was identified to be a triPeptide (PAY). Lipopolysaccharide treatment significantly (p
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Antioxidant and anti-Inflammatory Peptide fraction from salmon byproduct protein hydrolysates by peptic hydrolysis
Food Research International, 2012Co-Authors: Chang-bum Ahn, Young-sook ChoAbstract:Abstract Salmon byproduct protein was hydrolyzed with six proteases, and antioxidant activities of salmon byproduct protein hydrolysates (SPHs) were evaluated. The peptic hydrolysates from SPHs showed the highest antioxidant activity compared to that of the other protease hydrolysates, and were further fractionated into four fractions by size-exclusion chromatography. The SPH fractions (SPHFs) showed 2,2-diphenyl-1-picrylhydrazyl and hydrogen peroxide scavenging activity, and SPHF1 exhibited the highest antioxidant activity. SPHF1 contained 1000–2000 Da molecular weight Peptides and antioxidant amino acids such as Tyr, Phe, Pro, Ala, His, and Leu, which accounted for 28.62% of the total amino acids. SPHF1 showed no cytotoxic effects on Chang liver or RAW264.7 macrophage cells, and it significantly inhibited intracellular reactive oxygen species generation, lipid peroxidation, and enhanced the level of glutathione in Chang liver cells. Additionally, SPHF1 showed anti-Inflammatory activity by inhibiting nitric oxide production and proInflammatory cytokines including tumor necrosis factor-α, interleukin-6 and -1β in RAW264.7 macrophage cells.
Scott Poh - One of the best experts on this subject based on the ideXlab platform.
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Controlled release of anti-Inflammatory Peptides from reducible thermosensitive nanoparticles suppresses cartilage inflammation.
Nanomedicine : nanotechnology biology and medicine, 2016Co-Authors: Jenny B. Lin, Scott Poh, Alyssa PanitchAbstract:Characterized by pain, cartilage degradation, and inflammation, osteoarthritis is often treated with anti-Inflammatory therapies that provide short-term relief but can have adverse side effects; intra-articular drug delivery systems with controlled release of anti-Inflammatory Peptides using degradable poly(N-isopropylacrylamide) (pNIPAM) nanoparticles could prolong relief and minimize these side effects. Nanoparticles provide a biocompatible drug carrier that can protect encapsulated therapeutics from enzymatic degradation and increase payload delivery upon encountering a degradation stimulus. Here we demonstrate passive targeting of inflamed cartilage ex vivo by uptake of PEGylated pNIPAM nanoparticles with degradable disulfide crosslinks (abbreviated as NGPEGSS) into chondrocytes and subsequent intracellular release of an anti-Inflammatory Peptide KAFAKLAARLYRKALARQLGVAA (KAFAK). The KAFAK-loaded NGPEGSS treatment reduced ex vivo inflammation to a greater extent compared to its non-degradable counterparts. This study highlights a nanoparticle system that delivers therapeutics intracellularly with improved efficacy by triggered degradation and suppresses inflammation in multiple cell types within an inflamed joint.
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Release of Anti-Inflammatory Peptides from Thermosensitive Nanoparticles with Degradable Cross-Links Suppresses Pro-Inflammatory Cytokine Production
Biomacromolecules, 2015Co-Authors: Scott Poh, Jenny B. Lin, Alyssa PanitchAbstract:Pro-Inflammatory cytokines tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) are mediators in the development of many Inflammatory diseases. To demonstrate that macrophages take up and respond to thermosensitive nanoparticle drug carriers, we synthesized PEGylated poly(N-isopropylacrylamide-2-acrylamido-2-methyl-1-propanesulfonate) particles cross-linked with degradable disulfide (N,N′-bis(acryloyl)cystamine) (NGPEGSS). An anti-Inflammatory Peptide (KAFAK) was loaded and released from the thermosensitive nanoparticles and shown to suppress levels of TNF-α and IL-6 production in macrophages. Cellular uptake of fluorescent, thermosensitive, and degradable nanoparticles and therapeutic efficacy of free KAFAK Peptide compared to that of KAFAK loaded in PEGylated degradable thermosensitive nanoparticles were examined. The data suggests that the degradable, thermosensitive nanoparticles loaded with KAFAK may be an effective tool to treat Inflammatory diseases.
Jenny B. Lin - One of the best experts on this subject based on the ideXlab platform.
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Controlled release of anti-Inflammatory Peptides from reducible thermosensitive nanoparticles suppresses cartilage inflammation.
Nanomedicine : nanotechnology biology and medicine, 2016Co-Authors: Jenny B. Lin, Scott Poh, Alyssa PanitchAbstract:Characterized by pain, cartilage degradation, and inflammation, osteoarthritis is often treated with anti-Inflammatory therapies that provide short-term relief but can have adverse side effects; intra-articular drug delivery systems with controlled release of anti-Inflammatory Peptides using degradable poly(N-isopropylacrylamide) (pNIPAM) nanoparticles could prolong relief and minimize these side effects. Nanoparticles provide a biocompatible drug carrier that can protect encapsulated therapeutics from enzymatic degradation and increase payload delivery upon encountering a degradation stimulus. Here we demonstrate passive targeting of inflamed cartilage ex vivo by uptake of PEGylated pNIPAM nanoparticles with degradable disulfide crosslinks (abbreviated as NGPEGSS) into chondrocytes and subsequent intracellular release of an anti-Inflammatory Peptide KAFAKLAARLYRKALARQLGVAA (KAFAK). The KAFAK-loaded NGPEGSS treatment reduced ex vivo inflammation to a greater extent compared to its non-degradable counterparts. This study highlights a nanoparticle system that delivers therapeutics intracellularly with improved efficacy by triggered degradation and suppresses inflammation in multiple cell types within an inflamed joint.
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Release of Anti-Inflammatory Peptides from Thermosensitive Nanoparticles with Degradable Cross-Links Suppresses Pro-Inflammatory Cytokine Production
Biomacromolecules, 2015Co-Authors: Scott Poh, Jenny B. Lin, Alyssa PanitchAbstract:Pro-Inflammatory cytokines tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) are mediators in the development of many Inflammatory diseases. To demonstrate that macrophages take up and respond to thermosensitive nanoparticle drug carriers, we synthesized PEGylated poly(N-isopropylacrylamide-2-acrylamido-2-methyl-1-propanesulfonate) particles cross-linked with degradable disulfide (N,N′-bis(acryloyl)cystamine) (NGPEGSS). An anti-Inflammatory Peptide (KAFAK) was loaded and released from the thermosensitive nanoparticles and shown to suppress levels of TNF-α and IL-6 production in macrophages. Cellular uptake of fluorescent, thermosensitive, and degradable nanoparticles and therapeutic efficacy of free KAFAK Peptide compared to that of KAFAK loaded in PEGylated degradable thermosensitive nanoparticles were examined. The data suggests that the degradable, thermosensitive nanoparticles loaded with KAFAK may be an effective tool to treat Inflammatory diseases.