Functionalized Triblock Copolymer Vectors for the Treatment of Acute Lymphoblastic Leukemia.

The chemotherapeutic Parthenolide is an exciting new candidate for the treatment of acute lymphoblastic leukemia, but like many other small-molecule drugs, it has low aqueous solubility. As a consequence, Parthenolide can only be administered clinically in the presence of harmful cosolvents. Accordingly, we describe the synthesis, characterization, and testing of a range of biocompatible triblock copolymer micelles as particle-based delivery vectors for the hydrophobic drug Parthenolide. The drug-loaded particles are produced via an emulsion-to-micelle transition method, and the effects of introducing anionic and cationic surface charges on stability, drug sequestration, biocompatibility, and efficacy are investigated. Significantly, we demonstrate high levels of efficacy in the organic solvent-free systems against human mesenchymal stem cells and primary T-acute lymphoblastic leukemia patient cells, highlighting the effectiveness of the delivery vectors for the treatment of acute lymphoblastic leukemia.

Structure and properties of silicified purple membrane thin films.

Electrodeposited or evaporated thin films of purple membrane (PM) sheets comprising close packed arrays of bacteriorhodopsin demonstrate enhanced chemical stability and retention of photochromic and photovoltaic behavior when periodically intercalated with nanothin layers of aminopropyl-functionalized silica. In contrast, hybrid composites prepared from PM films infiltrated with nonorgano-functionalized silica are structurally nonintegrated, prone to cracking, and exhibit no photochromic or photoelectric properties. The results indicate that the presence of the aminopropyl functionality in the silica matrix facilitates formation of the intercalated nanostructure, increases the rates of B-state recovery and M-state decay in the photocycle, and enhances the photovoltage response. Changes in photoactivity suggest that the aminopropyl moiety acts as a strong proton donor/acceptor when intercalated between PM sheets. The ability to fabricate hybrid thin films of electrophoretically oriented PM sheets with enhanced physical and chemical properties could be important in the design of novel components for bacteriorhodopsin-based applications.

Chlorhexidine hexametaphosphate as a wound care material coating: antimicrobial efficacy, toxicity and effect on healing.

AIM: In this study, chlorhexidine hexametaphosphate (CHX-HMP) is investigated as a persistent antimicrobial coating for wound care materials. MATERIALS & METHODS: CHX-HMP was used as a wound care material coating and compared with chlorhexidine digluconate materials with respect to antimicrobial efficacy, toxicity and wound closure. RESULTS: Antimicrobial efficacy at day 1, 3 and 7 was observed with experimental and commercial materials. CHX-HMP coated materials had less toxic effect on human placental cells than commercial chlorhexidine dressings. CHX-HMP in pluronic gel did not delay healing but reduced wound colonization by E. faecalis. CONCLUSION: CHX-HMP could become a useful component of wound care materials with sustained antimicrobial efficacy, lower toxicity than chlorhexidine digluconate materials, and reduction in wound colonization without affecting closure.

Functionalization of ethylene vinyl acetate with antimicrobial chlorhexidine hexametaphosphate nanoparticles.

Ethylene vinyl acetate (EVA) is in widespread use as a polymeric biomaterial with diverse applications such as intravitreal devices, catheters, artificial organs, and mouthguards. Many biomaterials are inherently prone to bacterial colonization, as the human body is host to a vast array of microbes. This can lead to infection at the biomaterial's site of implantation or application. In this study, EVA was coated with chlorhexidine (CHX) hexametaphosphate (HMP) nanoparticles (NPs) precipitated using two different reagent concentrations: CHX-HMP-5 (5 mM CHX and HMP) and CHX-HMP-0.5 (0.5 mM CHX and HMP). Data gathered using dynamic light scattering, transmission electron microscopy, and atomic force microscopy indicated that the NPs were polydisperse, ~40-80 nm in diameter, and aggregated in solution to form clusters of ~140-200 nm and some much larger aggregates of 4-5 µM. CHX-HMP-5 formed large deposits on the polymer surface discernible using scanning electron microscopy, whereas CHX-HMP-0.5 did not. Soluble CHX was released by CHX-HMP-5 NP-coated surfaces over the experimental period of 56 days. CHX-HMP-5 NPs prevented growth of methicillin-resistant Staphylococcus aureus when applied to the polymer surfaces, and also inhibited or prevented growth of Pseudomonas aeruginosa with greater efficacy when the NP suspension was not rinsed from the polymer surface, providing a greater NP coverage. This approach may provide a useful means to treat medical devices fabricated from EVA to render them resistant to colonization by pathogenic microorganisms.

Synthesis, characterization, and efficacy of antimicrobial chlorhexidine hexametaphosphate nanoparticles for applications in biomedical materials and consumer products.

Chlorhexidine (CHX) is an antimicrobial agent that is efficacious against gram-negative and -positive bacteria and yeasts. Its mechanism of action is based on cell membrane disruption and, as such, it does not promote the development of bacterial resistance, which is associated with the widespread use of antibiotics. In this manuscript, we report the development of novel antimicrobial nanoparticles (NPs) based on a hexametaphosphate salt of CHX. These are synthesized by instantaneous reaction between equimolar aqueous solutions of CHX digluconate and sodium hexametaphosphate, under room temperature and pressure. The reaction results in a stable colloid composed of highly negatively charged NPs (-50 mV), of size 20-160 nm. The NPs adhere rapidly to specimens of glass, titanium, and an elastomeric wound dressing, in a dose-dependent manner. The functionalized materials exhibit a gradual leaching of soluble CHX over a period of at least 50 days. The NP colloid is efficacious against methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa in both planktonic and biofilm conditions. These NPs may find application in a range of biomedical and consumer materials.

Enzymatically active self-standing protein-polymer surfactant films prepared by hierarchical self-assembly.

Cross-linked protein-polymer surfactant films consisting of enzymatically active hybrid nanoclusters are prepared using a novel approach based on electrostatically mediated hierarchical self-assembly. The free-standing films are structurally robust, highly hydrophilic, and exhibit sustained fluorescence or recyclable enzymatic phosphatase or oxido-reductase behavior.

A new general synthetic strategy for phase-pure complex functional materials.

The ability of ionic liquids to solvate inorganic salts completely has to date never been employed in the synthesis of complex inorganic materials. Here, we demonstrate that complex functional oxides, even those traditionally considered extremely difficult to synthesize in bulk, such as quinternary superconductors, are produced with no impurity phases and on timescales that are much shorter than other synthetic techniques.