chondroitin-sulfates and maleimide

Chondroitin sulfate A-deoxycholic acid-polyethylene glycol-maleimide (CSA-DOCA-PEG-MAL; CDPM) nanostructures were designed for the transient binding of MAL with thiol in blood components and cell membranes, in addition to the CD44 receptor targeting, for the therapy of breast cancer. The spontaneous binding of free thiol groups in plasma proteins and blood cells with the MAL group of CDPM was significantly higher than that of CSA-DOCA-PEG (CDP). Enhanced cellular uptake and the in vitro antiproliferation efficacy of docetaxel (D)-loaded CDPM (CDPM/D) nanoparticles (NPs) in MCF-7 cells indicated dual-targeting effects based on MAL-thiol reactions and CSA-CD44 receptor interactions. Following intravenous injection in rats, reduced clearance and an elevated half-life of the drug was observed in the CDPM/D NPs compared to the CDP/D NPs. Taken together, MAL modification of CDP NPs could be a promising approach not only to enhance tumor targeting and penetration but also to extend the blood circulation time of anticancer drugs.

Topics: Animals; Antineoplastic Agents; Breast Neoplasms; Chondroitin Sulfates; Drug Carriers; Drug Liberation; Female; Humans; Hyaluronan Receptors; Maleimides; MCF-7 Cells; Nanoparticles; Particle Size; Polyethylene Glycols; Rats

Neural electrodes are an important part of brain-machine interface devices that can restore functionality to patients with sensory and movement disorders. Chronically implanted neural electrodes induce an unfavorable tissue response which includes inflammation, scar formation, and neuronal cell death, eventually causing loss of electrode function. We developed a poly(ethylene glycol) hydrogel coating for neural electrodes with non-fouling characteristics, incorporated an anti-inflammatory agent, and engineered a stimulus-responsive degradable portion for on-demand release of the anti-inflammatory agent in response to inflammatory stimuli. This coating reduces in vitro glial cell adhesion, cell spreading, and cytokine release compared to uncoated controls. We also analyzed the in vivo tissue response using immunohistochemistry and microarray qRT-PCR. Although no differences were observed among coated and uncoated electrodes for inflammatory cell markers, lower IgG penetration into the tissue around PEG+IL-1Ra coated electrodes indicates an improvement in blood-brain barrier integrity. Gene expression analysis showed higher expression of IL-6 and MMP-2 around PEG+IL-1Ra samples, as well as an increase in CNTF expression, an important marker for neuronal survival. Importantly, increased neuronal survival around coated electrodes compared to uncoated controls was observed. Collectively, these results indicate promising findings for an engineered coating to increase neuronal survival and improve tissue response around implanted neural electrodes.

Topics: Amino Acid Sequence; Animals; Astrocytes; Blood-Brain Barrier; Cell Adhesion; Cell Survival; Cells, Cultured; Chondroitin Sulfates; Coated Materials, Biocompatible; Electrodes, Implanted; Gene Expression Regulation; Glial Fibrillary Acidic Protein; Hydrogel, Polyethylene Glycol Dimethacrylate; Immunoglobulin G; Inflammation Mediators; Interleukin 1 Receptor Antagonist Protein; Lipopolysaccharides; Male; Maleimides; Microglia; Molecular Sequence Data; Neurons; Peptide Hydrolases; Polyethylene Glycols; Rats, Sprague-Dawley; Surface Properties