Synthesis of 1,8-naphthalimide-based probes with fluorescent switch triggered by flufenamic acid

This work was supported by the European Commission Marie Curie IEF NANOGEND (ga 299266) to DV and the European Commission Marie Curie ITN NANODRUG (ga 289454) to GS

Sorting live stem cells based on Sox2 mRNA expression.

PMCID: PMC3507951This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.While cell sorting usually relies on cell-surface protein markers, molecular beacons (MBs) offer the potential to sort cells based on the presence of any expressed mRNA and in principle could be extremely useful to sort rare cell populations from primary isolates. We show here how stem cells can be purified from mixed cell populations by sorting based on MBs. Specifically, we designed molecular beacons targeting Sox2, a well-known stem cell marker for murine embryonic (mES) and neural stem cells (NSC). One of our designed molecular beacons displayed an increase in fluorescence compared to a nonspecific molecular beacon both in vitro and in vivo when tested in mES and NSCs. We sorted Sox2-MB(+)SSEA1(+) cells from a mixed population of 4-day retinoic acid-treated mES cells and effectively isolated live undifferentiated stem cells. Additionally, Sox2-MB(+) cells isolated from primary mouse brains were sorted and generated neurospheres with higher efficiency than Sox2-MB(-) cells. These results demonstrate the utility of MBs for stem cell sorting in an mRNA-specific manner

PEG-b-PPS diblock copolymer aggregates for hydrophobic drug solubilization and release: cyclosporin A as an example

Micelles formed from amphiphilic block copolymers have been explored in recent years as carriers for hydrophobic drugs. In an aqueous environment, the hydrophobic blocks form the core of the micelle, which can host lipophilic drugs, while the hydrophilic blocks form the corona or outer shell and stabilize the interface between the hydrophobic core and the external medium. In the present work, mesophase behavior and drug encapsulation were explored in the AB block copolymeric amphiphile composed of poly(ethylene glycol) (PEG) as a hydrophile and poly(propylene sulfide) PPS as a hydrophobe, using the immunosuppressive drug cyclosporin A (CsA) as an example of a highly hydrophobic drug. Block copolymers with a degree of polymerization of 44 on the PEG and of 10, 20 and 40 on the PPS respectively (abbreviated as PEG44-b-PPS10, PEG44-b-PPS20, PEG44-b-PPS40) were synthesized and characterized. Drug-loaded polymeric micelles were obtained by the cosolvent displacement method as well as the remarkably simple method of dispersing the warm polymer melt, with drug dissolved therein, in warm water. Effective drug solubility up to 2 mg/mL in aqueous media was facilitated by the PEG- b-PPS micelles, with loading levels up to 19% w/w being achieved. Release was burst-free and sustained over periods of 9-12 days. These micelles demonstrate interesting solubilization characteristics, due to the low glass transition temperature, highly hydrophobic nature, and good solvent properties of the PPS bloc

Probes characterisation from Synthesis of 1,8-naphthalimide-based probes with fluorescent switch triggered by flufenamic acid

NMR, LC-MS and UV-Vis spectra of probes 1, 2, and

Extracellular matrix binding mixed micelles for drug delivery applications

Received 5 January 2009 Accepted 22 March 2009 Available online 27 March 2009 Keywords: Mixed micelles Drug delivery Block copolymers Sirolimus Extracellular matrix We present the formation of collagen-binding mixed micelles and their potential suitability to deliver therapeutic drugs to the vessel wall. We modified poly(ethylene oxide)-bl-poly(propylene oxide)- bl- poly(ethylene oxide) (Pluronic F-127) to display sulfate groups on the terminus of the PEO block to act as a heparin mimics and bind to collagen in the extracellular matrix. This functionalized macroamphiphile was incorporated into a mixed micelle with poly(propylene sulfide)-bl-poly(ethylene oxide), a macroamphi- phile that demonstrates improved micellar stability relative to Pluronic F-127 micelles. The mixed micelles were examined using analytical ultracentrifugation, dynamic light scattering, transmission electron microscopy, and measures of the critical micellar concentration using surface tensiometry. Encapsulation and in vitro release of Sirolimus, an immunosuppressant drug of interest in coronary artery treatment, was considered as an example. Mixed micelles with the sulfate functionality demonstrated enhanced binding to collagen I coated surfaces, suggestive of the potential for binding to the extracellular milieu

Controlled Release Drug Coatings on Flexible Neural Probes

We present the development, characterization and in vivo validation of a novel drug eluting coating that has been applied to flexible neural probes. The coating consists of drug eluting nanoparticles loaded with an anti-inflammatory drug embedded in a biodegradable polymer. The drug eluting coating is applied to flexible polymer neural probes with platinum electrodes. The drug eluting device is implanted in one hemisphere of a rat, while a control device is implanted in the opposite hemisphere. Impedance measurements are performed to determine the effect of the drug eluting coating on the tissue reaction surrounding the probe and the electrical characteristics of the devices. Probes that are coated with drug eluting coatings show better long term impedance characteristics over control probes. These coatings can be used to increase the reliability and long term success of neural prostheses

Hierarchical Self-assembly of Amphiphilic Calix[6]arene Wheels and Viologen Axles in Water

We have designed and synthesized two amphiphilic calix[6]arene derivatives, CA8 and CA18, that combine the potential to act as wheel components for pseudorotaxane structures with the self-assembly features typical of surfactant molecules in aqueous solution. Their endo-cavity recognition and self-aggregation properties were compared with those of a non-amphiphilic analogue, C8. TEM, DLS, and fluorescence experiments show that in water the amphiphilic calixarenes form vesicle- and micelle-like aggregates. The size, nature and properties of such aggregates depend on the length of the alkyl chain anchored at the lower rim of the calix[6]arene skeleton, as well as on the inclusion of a molecular guest into the wheel. Specifically, the release of a fluorescent guest entrapped inside the CA8 vesicles is accelerated in the presence of dioctylviologen axles that can pierce the calixarene cavity