Cardiopoietic cell therapy for advanced ischemic heart failure: results at 39 weeks of the prospective, randomized, double blind, sham-controlled CHART-1 clinical trial

Cardiopoietic cells, produced through cardiogenic conditioning of patients' mesenchymal stem cells, have shown preliminary efficacy. The Congestive Heart Failure Cardiopoietic Regenerative Therapy (CHART-1) trial aimed to validate cardiopoiesis-based biotherapy in a larger heart failure cohort

Governing the European security and defence policy (ESDP) : an institutionalist perspective on the European Union's military crisis management in the context of operations concordia (FYROM 2003) and Artemis (DR Congo 2003)

EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Evaluation of antioxidant activity of caffeic acid phenethyl ester loaded block copolymer micelles

Caffeic acid phenethyl ester (CAPE), a hydrophobic constituent of poplar propolis of valuable biological activity, was immobilized in poly(ethylene oxide)-b-poly(ε-caprolactone)-b-poly(ethylene oxide) (PEO-b-PCL-b-PEO) copolymer micelles to improve its solubility in water. CAPE was loaded in the micelles by dialysis, achieving ca. 50% encapsulation efficiency. The drug loaded micelles were characterized with a mean diameter of 39 nm, narrow size distribution and slightly positive zeta-potential (approximately 2 mV). The in vitro release profile showed an improved dissolution behavior of micellar CAPE than pure CAPE. In vitro studies on human hepatoma HepG2 and neuronal SH-SY5Y cells demonstrated that the empty PEO-b-PCL-b-PEO micelles were not cytotoxic, whereas the drug loaded micelles exerted cytotoxic effects proportional to CAPE content. The protective activity of pure and micellar CAPE was investigated in a model of H2O2 induced oxidative damage in HepG2 and SH-SY5Y cells. In both cell types, micellar CAPE exhibited better protective activity against the oxidative damage than pure CAPE at very low concentrations (0.1 µg/mL), which is far from the cytotoxic concentration of CAPE-loaded micelles (71 µg/mL). Consequently, the developed micellar formulation has an improved activity against oxidative damage in hepatic and neuronal cells as comparing to pure CAPE

Incorporation of Resveratrol in Polymeric Nanogel for Improvement of Its Protective Effects on Cellular and Microsomal Oxidative Stress Models

Nanogels are attractive drug delivery systems that provide high loading capacity for drug molecules, improve their stability, and increase cellular uptake. Natural antioxidants, especially polyphenols such as resveratrol, are distinguished by low aqueous solubility, which hinders therapeutic activity. Thus, in the present study, resveratrol was incorporated into nanogel particles, aiming to improve its protective effects in vitro. The nanogel was prepared from natural substances via esterification of citric acid and pentane-1,2,5-triol. High encapsulation efficiency (94.5%) was achieved by applying the solvent evaporation method. Dynamic light scattering, atomic force microscopy, and transmission electron microscopy revealed that the resveratrol-loaded nanogel particles were spherical in shape with nanoscopic dimensions (220 nm). In vitro release tests showed that a complete release of resveratrol was achieved for 24 h, whereas at the same time the non-encapsulated drug was poorly dissolved. The protective effect of the encapsulated resveratrol against oxidative stress in fibroblast and neuroblastoma cells was significantly stronger compared to the non-encapsulated drug. Similarly, the protection in a model of iron/ascorbic acid-induced lipid peroxidation on rat liver and brain microsomes was higher with the encapsulated resveratrol. In conclusion, embedding resveratrol in this newly developed nanogel improved its biopharmaceutical properties and protective effects in oxidative stress models

Incorporation of Resveratrol-Hydroxypropyl-β-Cyclodextrin Complexes into Hydrogel Formulation for Wound Treatment

Resveratrol could be applied in wound healing therapies because of its antioxidant, anti-inflammatory and antibacterial effects. However, the main limitation of resveratrol is its low aqueous solubility. In this study, resveratrol was included in hydroxypropyl-β-cyclodextrin complexes and further formulated in Pluronic F-127 hydrogels for wound treatment therapy. IR-spectroscopy and XRD analysis confirmed the successful incorporation of resveratrol into complexes. The wound-healing ability of these complexes was estimated by a scratch assay on fibroblasts, which showed a tendency for improvement of the effect of resveratrol after complexation. The antimicrobial activity of resveratrol in aqueous dispersion and in the complexes was evaluated on methicillin-resistant Staphylococcus aureus (MRSA), Escherichia coli, and Candida albicans strains. The results revealed a twofold decrease in the MIC and stronger inhibition of the metabolic activity of MRSA after treatment with resveratrol in the complexes compared to the suspended drug. Furthermore, the complexes were included in Pluronic hydrogel, which provided efficient drug release and appropriate viscoelastic properties. The formulated hydrogel showed excellent biocompatibility which was confirmed via skin irritation test on rabbits. In conclusion, Pluronic hydrogel containing resveratrol included in hydroxypropyl-β-cyclodextrin complexes is a promising topical formulation for further studies directed at wound therapy