Publications by authors named "Meredith Mintzer"

An evidence-based systematic review of active hexose correlated compound (AHCC) by the Natural Standard Research Collaboration consolidates the safety and efficacy data available in the scientific literature using a validated, reproducible grading rationale. This article includes written and statistical analysis of clinical trials, plus a compilation of expert opinion, folkloric precedent, history, pharmacology, kinetics/dynamics, interactions, adverse effects, toxicology, and dosing.

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An evidence-based systematic review of vanadium by the Natural Standard Research Collaboration consolidates the safety and efficacy data available in the scientific literature using a validated, reproducible grading rationale. This article includes written and statistical analysis of clinical trials, plus a compilation of expert opinion, folkloric precedent, history, pharmacology, kinetics/dynamics, interactions, adverse effects, toxicology, and dosing.

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The emergence and re-emergence of bacterial strains that are resistant to current antibiotics reveal the clinical need for new agents that possess broad-spectrum antibacterial activity. Furthermore, bacteriophobic coatings that repel bacteria are important for medical devices, as the lifetime, reliability, and performance of implant devices are hindered by bacterial adhesion and infection. Dendrimers, a specific class of monodisperse macromolecules, have recently shown potential to function as both antibacterial agents and antimicrobial surface coatings.

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This study aimed to identify suitable siRNA delivery systems based on flexible generation 2-4 triazine dendrimers by correlating physico-chemical and biological in vitro and in vivo properties of the complexes with thermodynamic parameters calculated using molecular modeling. The siRNA binding properties of the dendrimers and PEI 25 kDa were simulated, binding and stability were measured in SYBR Gold assays, and hydrodynamic diameters, zeta potentials, and cytotoxicity were quantified. These parameters were compared with cellular uptake of the complexes and their ability to mediate RNAi.

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Since their development in the mid-80s, dendrimers have become prominent synthetic macromolecules in the field of biomedical science. This tutorial review begins by discussing pertinent background information about dendrimers, focusing on their behavior in solution, how they are synthesized and what advantages they have over linear polymers. Then the focus of the review shifts to the biomedical applications of dendrimers, including their use in drug delivery, tissue engineering, gene transfection, and contrast enhancement for magnetic resonance imaging.

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A family of triazine dendrimers, differing in their core flexibility, generation number, and surface functionality, was prepared and evaluated for its ability to accomplish RNAi. The dendriplexes were analyzed with respect to their physicochemical and biological properties, including condensation of siRNA, complex size, surface charge, cellular uptake and subcellular distribution, their potential for reporter gene knockdown in HeLa/Luc cells, and ultimately their stability, biodistribution, pharmacokinetics and intracellular uptake in mice after intravenous (iv) administration. The structure of the backbone was found to significantly influence siRNA transfection efficiency, with rigid, second generation dendrimers displaying higher gene knockdown than the flexible analogues while maintaining less off-target effects than Lipofectamine.

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To combine benefits stemming from the high nucleophilicity of piperidine and the flexibility afforded by aliphatic triamine linkers, a trimethylene-dipiperidine linker has been used to synthesize triazine dendrimers using a divergent route. The cyclic, secondary amine of the linker reacts with monochlorotriazine monomer units, , leading to a dendrimer growth strategy that requires two-steps-per-generation. This strategy reduces the number of steps required for synthesis by 50%.

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Using a macromonomer, first, third, and fifth generation triazine dendrimers can be prepared using a divergent approach. The nine-step process to the fifth generation target relies on an iterative two-reactions-per-generation strategy to yield the desired material in approximately 48% overall yield. This target displays 96 surface groups.

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In this study, simulation challenges intuitive models of "flexible" and "rigid" generation two triazine dendrimers as it pertains to solution conformation and conformation on binding DNA or siRNA sequences. These results derive from structural and energetic analyses of the binding events. Simulations of the rigid structure reinforce the role of the constrained piperazine linker in positioning the peripheral groups at significant distance from each other and the core of the dendrimer.

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A panel of eight, second generation triazine dendrimers differing in the number of amines, guanidines, hydroxyls and aliphatic groups on the periphery was synthesized and assayed for gene transfer in an attempt to correlate the effects of surface functionality on transfection efficiency. The physicochemical and biological properties of the dendrimers and dendriplexes, such as condensation of DNA, size, surface charge and morphology of dendriplexes, toxicity and ultimately transfection efficiency in MeWo cells, were analyzed. The results from an ethidium bromide exclusion assay showed that the complexation efficiency of the dendrimers with DNA is moderately affected by surface groups.

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A family of generation 1, 2, and 3 triazine dendrimers differing in their core flexibility was prepared and evaluated for their ability to accomplish gene transfection. Dendrimers and dendriplexes were analyzed by their physicochemical and biological properties such as condensation of DNA, size, surface charge, morphology of dendriplexes, toxic and hemolytic effects, and ultimately transfection efficiency in L929 and MeWo cells. Flexibility of the backbone was found to play an important role with generation 2 dendrimer displaying higher transfection efficiencies than 25 kDa poly(ethylene imine) or SuperFect at a lower cytotoxicity level.

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