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Arthritis micelle

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https://www.readbyqxmd.com/read/28991483/vasoactive-intestinal-peptide-nanomedicine-for-the-management-of-inflammatory-bowel-disease
#1
Dulari Jayawardena, Arivarasu N Anbazhagan, Grace Guzman, Pradeep K Dudeja, Hayat Onyuksel
Inflammatory bowel disease (IBD) is a chronic relapsing disorder of the intestine, with increasing incidence worldwide. At present, the management of IBD is an unmet medical need due to the ineffectiveness of currently available drugs in treating all patients, and there is strong demand for novel therapeutics. In this regard, vasoactive intestinal peptide, a potent anti-inflammatory endogenous hormone, has shown promise in managing multiple immune disorders in animal models. However, when administered in the free form, VIP undergoes rapid degradation in vivo, and with continuous infusion, it causes severe dose limiting side effects...
October 19, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28837059/novel-drug-delivery-systems-tailored-for-improved-administration-of-glucocorticoids
#2
REVIEW
Fred Lühder, Holger M Reichardt
Glucocorticoids (GC) are one of the most popular and versatile classes of drugs available to treat chronic inflammation and cancer, but side effects and resistance constrain their use. To overcome these hurdles, which are often related to the uniform tissue distribution of free GC and their short half-life in biological fluids, new delivery vehicles have been developed including PEGylated liposomes, polymeric micelles, polymer-drug conjugates, inorganic scaffolds, and hybrid nanoparticles. While each of these nanoformulations has individual drawbacks, they are often superior to free GC in many aspects including therapeutic efficacy when tested in cell culture or animal models...
August 24, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28457963/development-of-a-local-anesthetic-lidocaine-loaded-redox-active-injectable-gel-for-postoperative-pain-management
#3
Yukio Nagasaki, Yutaro Mizukoshi, Zhenyu Gao, Chitho P Feliciano, Kyungho Chang, Hiroshi Sekiyama, Hiroyuki Kimura
Although local anesthesia is commonly applied for pain relief, there are several issues such as its short duration of action and low effectiveness at the areas of inflammation due to the acidic pH. The presence of excessive amount of reactive oxygen species (ROS) is known to induce inflammation and aggravate pain. To resolve these issues, we developed a redox-active injectable gel (RIG) with ROS-scavenging activity. RIG was prepared by mixing polyamine-b-poly(ethylene glycol)-b-polyamine with nitroxide radical moieties as side chains on the polyamine segments (PMNT-b-PEG-b-PMNT) with a polyanion, which formed a flower-type micelle via electrostatic complexation...
April 27, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28250648/the-influence-of-pluronic-f68-and-f127-nanocarrier-on-physicochemical-properties-in-vitro-release-and-antiproliferative-activity-of-thymoquinone-drug
#4
Salwa Shaarani, Shahrul Sahul Hamid, Noor Haida Mohd Kaus
BACKGROUND: This study reports on hydrophobic drug thymoquinone (TQ), an active compound found in the volatile oil of Nigella sativa that exhibits anticancer activities. Nanoformulation of this drug could potentially increase its bioavailability to specific target cells. OBJECTIVE: The aim of this study was to formulate TQ into polymer micelle, Pluronic F127 (5.0 wt %) and Pluronic F68 (0.1 wt %), as a drug carrier to enhance its solubility and instability in aqueous media...
January 2017: Pharmacognosy Research
https://www.readbyqxmd.com/read/28107661/targeting-nf-kb-signaling-with-polymeric-hybrid-micelles-that-co-deliver-sirna-and-dexamethasone-for-arthritis-therapy
#5
Qin Wang, Hao Jiang, Yan Li, Wenfei Chen, Hanmei Li, Ke Peng, Zhirong Zhang, Xun Sun
The transcription factor NF-kB plays a pivotal role in the pathogenesis of rheumatoid arthritis. Here we attempt to slow arthritis progression by co-delivering the glucocorticoid dexamethasone (Dex) and small-interfering RNA targeting NF-kB p65 using our previously developed polymeric hybrid micelle system. These micelles contain two similar amphiphilic copolymers: polycaprolactone-polyethylenimine (PCL-PEI) and polycaprolactone-polyethyleneglycol (PCL-PEG). The hybrid micelles loaded with Dex and siRNA effectively inhibited NF-kB signaling in murine macrophages more efficiently than micelles containing either Dex or siRNA on their own...
January 11, 2017: Biomaterials
https://www.readbyqxmd.com/read/28068545/design-preparation-and-characterization-of-ph-responsive-prodrug-micelles-with-hydrolyzable-anhydride-linkages-for-controlled-drug-delivery
#6
Girija Seetharaman, Adarsh R Kallar, Vineeth M Vijayan, Jayabalan Muthu, Shivaram Selvam
We report a new prodrug micelle-based approach in which a model hydrophobic non-steroidal anti-inflammatory drug (NSAID), ibuprofen (Ibu), is tethered to amphiphilic methoxy polyethylene glycol-polypropylene fumarate (mPEG-PPF) diblock copolymer via hydrolytic anhydride linkages for potential controlled release applications of NSAIDs. Synthesized mPEG-PPF-Ibu polymer drug conjugates (PDCs) demonstrated high drug conjugation efficiency (∼90%) and self-assembled to form micellar nanostructures in aqueous medium with critical micelle concentrations ranging between 16 and 30μg/mL...
April 15, 2017: Journal of Colloid and Interface Science
https://www.readbyqxmd.com/read/28038947/ph-sensitive-polymeric-micelles-for-targeted-delivery-to-inflamed-joints
#7
Chunhong Li, Hanmei Li, Qin Wang, Meiling Zhou, Man Li, Tao Gong, Zhirong Zhang, Xun Sun
Effective treatment for rheumatoid arthritis is hindered by the lack of drugs that selectively target inflamed joints. Liposomes, nanoparticles and conventional micelles loaded with limited amounts of drugs may be unstable in the circulation and result in uncontrolled drug release kinetics. Here we developed a new drug delivery system of pH-sensitive polymeric micelles based on an acid-labile hydrazone bond. Amphiphilic conjugates of a PEG-based derivative and the hydrophobic drug prednisolone (PD) self-assembled into PD micelles with a drug loading of 19...
January 28, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/27765724/systemic-delivery-of-small-interfering-rna-targeting-nuclear-factor-%C3%AE%C2%BAb-in-mice-with-collagen-induced-arthritis-using-arginine-histidine-cysteine-based-oligopeptide-modified-polymer-nanomicelles
#8
Takanori Kanazawa, Takahiro Endo, Naoki Arima, Hisako Ibaraki, Yuuki Takashima, Yasuo Seta
This study aimed to build an innovative system to deliver a systemic small interfering RNA (siRNA) treatment for rheumatoid arthritis. We combined arginine-histidine-cysteine based oligopeptide-modified polymer micelles with siRNA targeting the nuclear factor κB subunit, RelA (siRelA). This is a key molecule in the control of inflammation. We tested the cellular uptake of siRNA and its effects on inflammatory cytokine levels in vitro using synoviocytes, and siRNA distribution and therapeutic effects in vivo in mice with collagen-induced arthritis (CIA)...
December 30, 2016: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/27565213/folate-receptor-targeted-three-layered-micelles-and-hydrogels-for-gene-delivery-to-activated-macrophages
#9
Mariam Mohammadi, Ying Li, Daniel G Abebe, Yuran Xie, Rima Kandil, Teresa Kraus, Nardhy Gomez-Lopez, Tomoko Fujiwara, Olivia M Merkel
New folic acid (FA) coupled three layered micelles (3LM) were designed to encapsulate DNA, and their application as delivery system that specifically targets activated macrophages was investigated for new treatment options in rheumatoid arthritis (RA). FA coupled poly(l-lactide)-b-poly(ethylene glycol) (FA-PEG-PLLA) was synthesized via the NHS-ester activated/amine coupling method. Fluorescein labeled folic acid was used for flow cytometric detection of the expression of functional folic receptor β in LPS-activated and resting macrophages...
December 28, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/27139142/comparison-of-pharmaceutical-nanoformulations-for-curcumin-enhancement-of-aqueous-solubility-and-carrier-retention
#10
COMPARATIVE STUDY
Iris E Allijn, Raymond M Schiffelers, Gert Storm
Curcumin, originally used in traditional medicine and as a spice, is one of the most studied and most popular natural products of the past decade. It has been described to be an effective anti-inflammatory and anti-cancer drug and protects against chronic diseases such as rheumatoid arthritis and atherosclerosis. Despite these promising pharmacological properties, curcumin is also very lipophilic, which makes its formulation challenging. Ideally the nanocarrier should additionally also retain the encapsulated curcumin to provide target tissue accumulation...
June 15, 2016: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/27057749/targeted-delivery-of-low-dose-dexamethasone-using-pcl-peg-micelles-for-effective-treatment-of-rheumatoid-arthritis
#11
Qin Wang, Jiayu Jiang, Wenfei Chen, Hao Jiang, Zhirong Zhang, Xun Sun
Glucocorticoid (GC) is the cornerstone therapy of rheumatoid arthritis, but high doses are associated with serious adverse effects. In an effort to improve the efficacy of low-dose GC therapy, we developed a micelle system for targeted delivery to inflamed joints and validated the approach in a rat model of arthritis. Micelles loaded with dexamethasone (Dex) self-assembled from the amphipathic poly (ethylene glycol)-block-poly (ε-caprolactone) (PCL-PEG) polymer via film dispersion, and they were injected intravenously at a dose of only 0...
May 28, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/26472611/poly-ethylene-glycol-b-poly-lysine-copolymer-bearing-nitroaromatics-for-hypoxia-sensitive-drug-delivery
#12
Thavasyappan Thambi, Soyoung Son, Doo Sung Lee, Jae Hyung Park
UNLABELLED: Hypoxia occurs in a variety of pathological conditions including stroke, rheumatoid arthritis, atherosclerosis, and tumors. In this study, an amphiphilic block copolymer, composed of poly(ethylene glycol) as the hydrophilic block and poly(ε-(4-nitro)benzyloxycarbonyl-L-lysine) as the hydrophobic block, was prepared for hypoxia-sensitive drug delivery. Owing to its amphiphilic nature, the block copolymer formed micelles and encapsulated doxorubicin (DOX) in an aqueous condition...
January 2016: Acta Biomaterialia
https://www.readbyqxmd.com/read/26181632/antiinflammatory-activity-of-a-novel-folic-acid-targeted-conjugate-of-the-mtor-inhibitor-everolimus
#13
Yingjuan Lu, Nikki Parker, Paul J Kleindl, Vicky A Cross, Kristin Wollak, Elaine Westrick, Torian W Stinnette, Mark A Gehrke, Kevin Wang, Hari Krishna R Santhapuram, Fei You, Spencer J Hahn, Jeremy F Vaughn, Patrick J Klein, Iontcho R Vlahov, Philip S Low, Christopher P Leamon
Folate receptor (FR)-β has been identified as a promising target for antimacrophage and antiinflammatory therapies. In the present study, we investigated EC0565, a folic acid-derivative of everolimus, as a FR-specific inhibitor of the mammalian target of rapamycin (mTOR). Because of its amphiphilic nature, EC0565 was first evaluated for water solubility, critical micelle formation, stability in culture and FR-binding specificity. Using FR-expressing macrophages, the effect of EC0565 on mTOR signaling and cellular proliferation was studied...
2015: Molecular Medicine
https://www.readbyqxmd.com/read/25629290/hydrophobic-cyanine-dye-doped-micelles-for-optical-in-vivo-imaging-of-plasma-leakage-and-vascular-disruption
#14
Bálint Botz, Kata Bölcskei, Ágnes Kemény, Zoltán Sándor, Valéria Tékus, György Sétáló, Janka Csepregi, Attila Mócsai, Erika Pintér, László Kollár, Zsuzsanna Helyes
Vascular leakage is an important feature of various disease conditions. In vivo optical imaging provides a great opportunity for the evaluation of this phenomenon. In the present study, we focus on the development and validation of a near-infrared (NIR) imaging formula to allow reliable, cost-efficient evaluation of vascular leakage in diverse species using the existing small-animal fluorescence imaging technology. IR-676, a moderately hydrophobic NIR cyanine dye, was doped into self-assembling aqueous micelles using a widely employed and safe nonionic emulsifier (Kolliphor HS 15), and was tested in several acute and chronic inflammatory disease models in both mice and rats...
January 2015: Journal of Biomedical Optics
https://www.readbyqxmd.com/read/25532847/design-and-optimisation-of-bioactive-cyclic-peptides-generation-of-a-down-regulator-of-tnf-secretion
#15
Roger New, Gurpal S Bansal, Malgorzata Dryjska, Michal Bogus, Patricia Green, Marc Feldmann, Fionula Brennan
Although strong binding interactions between protein receptor and ligand do not require the participation of a large number of amino acids in either site, short peptide chains are generally poor at recreating the types of protein-protein interactions which take place during cell recognition and signalling process, probably because their flexible backbones prevent the side chains from forming sufficiently rigid and stable epitopes, which can take part in binding with the desired strength and specificity. In a recently-reported study, it was shown that a proto-epitope containing F, R and S amino acids has the ability to down-regulate TNF secretion by macrophages...
2014: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/25433956/how-to-mechanistically-explain-the-condor-study-data
#16
C M Spies, E Stemmler, F Buttgereit
Results of the CONDOR study suggest that in osteoarthritis and rheumatoid arthritis patients at elevated risk of gastrointestinal (GI) events, treatment with celecoxib, a cyclooxygenase (COX)-2 selective non-steroidal anti-inflammatory drug (NSAID), demonstrated significantly lower toxicity in the upper and lower (GI) tract when compared to the non-selective NSAID diclofenac plus a proton-pump-inhibitor (PPI), omeprazole. According to current knowledge, traditional NSAIDs (tNSAIDs) as non-selective COX-inhibitors exert their damaging effects on the upper GI tract, largely by reduction of the COX-1 related synthesis of gastro-protective prostaglandins...
January 2015: Medical Hypotheses
https://www.readbyqxmd.com/read/25236343/could-albumin-affect-the-self-assembling-properties-of-a-block-co-polymer-system-and-drug-release-an-in-vitro-study
#17
Diego R Perinelli, Giulia Bonacucina, Stefania Pucciarelli, Marco Cespi, Luca Casettari, Valeria Polzonetti, Francesco Martino Carpi, Giovanni F Palmieri
PURPOSE: This work investigated the influence of a model protein, bovine serum albumin (BSA), on the properties of a thermogelling formulation intended for administration inside body compartments where there is high albumin content, as in the case of inflamed joints; it also explored the relation between the variation of these properties and release performance of methotrexate (MTX), a drug used to treat forms of arthritis and rheumatic conditions. METHODS: The influence of BSA on the micellisation and gelation behaviour of Poloxamer 407, chosen as a model copolymer, was studied by differential scanning calorimetry (microDSC), dynamic light scattering (DLS), fluorescence spectroscopy and rheology studies...
March 2015: Pharmaceutical Research
https://www.readbyqxmd.com/read/25152071/inhibition-of-group-iva-cytosolic-phospholipase-a2-by-thiazolyl-ketones-in-vitro-ex-vivo-and-in-vivo
#18
George Kokotos, Astrid J Feuerherm, Efrosini Barbayianni, Ishita Shah, Mari Sæther, Victoria Magrioti, Thuy Nguyen, Violetta Constantinou-Kokotou, Edward A Dennis, Berit Johansen
Group IVA cytosolic phospholipase A2 (GIVA cPLA2) is the rate-limiting provider of pro-inflammatory mediators in many tissues and is thus an attractive target for the development of novel anti-inflammatory agents. In this work, we present the synthesis of new thiazolyl ketones and the study of their activities in vitro, in cells, and in vivo. Within this series of compounds, methyl 2-(2-(4-octylphenoxy)acetyl)thiazole-4-carboxylate (GK470) was found to be the most potent inhibitor of GIVA cPLA2, exhibiting an XI(50) value of 0...
September 25, 2014: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/24341611/nanomedicines-for-inflammatory-arthritis-head-to-head-comparison-of-glucocorticoid-containing-polymers-micelles-and-liposomes
#19
COMPARATIVE STUDY
Lingdong Quan, Yijia Zhang, Bart J Crielaard, Anand Dusad, Subodh M Lele, Cristianne J F Rijcken, Josbert M Metselaar, Hana Kostková, Tomáš Etrych, Karel Ulbrich, Fabian Kiessling, Ted R Mikuls, Wim E Hennink, Gert Storm, Twan Lammers, Dong Wang
As an emerging research direction, nanomedicine has been increasingly utilized to treat inflammatory diseases. In this head-to-head comparison study, four established nanomedicine formulations of dexamethasone, including liposomes (L-Dex), core-cross-linked micelles (M-Dex), slow releasing polymeric prodrugs (P-Dex-slow), and fast releasing polymeric prodrugs (P-Dex-fast), were evaluated in an adjuvant-induced arthritis rat model with an equivalent dose treatment design. It was found that after a single i.v...
January 28, 2014: ACS Nano
https://www.readbyqxmd.com/read/24157475/redox-active-injectable-gel-using-thermo-responsive-nanoscale-polyion-complex-flower-micelle-for-noninvasive-treatment-of-local-inflammation
#20
Min Ley Pua, Toru Yoshitomi, Pennapa Chonpathompikunlert, Aki Hirayama, Yukio Nagasaki
Reactive oxygen species (ROS) scavengers have not been widely used for treatment of local inflammatory reactions such as arthritis and periodontal disease because they are rapidly eliminated from the inflamed site, which results in a low therapeutic effect. Therefore, to enhance the local retention time of ROS scavengers, we developed a redox-active injectable gel (RIG) system by using poly[4-(2,2,6,6-tetramethylpiperidine-N-oxyl)aminomethylstyrene]-b-poly(ethylene glycol)-b-poly[4-(2,2,6,6-tetramethylpiperidine-N-oxyl)aminomethylstyrene] (PMNT-PEG-PMNT) triblock copolymer, which possesses ROS scavenging nitroxide radicals as side chains of the PMNT segment...
December 28, 2013: Journal of Controlled Release: Official Journal of the Controlled Release Society
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