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Syntheses of vinylsilyl alcohols having one to three vinyl moieties and their use as initiators for ethylene oxide polymerizations are discussed. Poly(ethylene oxide) oligomers with vinylsilanes at one end and a hydroxyl group at the other were prepared in base-catalyzed reactions. Molecular weights determined from 1H NMR and gel permeation chromatography were close to the targeted values. Carboxylic acid functional poly(ethylene oxide) oligomers were prepared from ene-thiol addition reactions of mercaptoacetic acid across the vinylsilane terminus. It is anticipated that these carboxylic acid functional oligomers will complex to magnetite nanoparticles to afford complexes that can be dispersed in aqueous media.

Core-shell nanostructures with nonionic amphiphilic shells and ionic cores encapsulating gentamicin were designed for therapy against intracellular pathogens, including Salmonella and Listeria. Flow cytometry and confocal microscopy showed that their uptake into J774A.1 macrophages proceeded mainly by fluid-phase endocytosis and clathrin-mediated pathways. The nanostructures were nontoxic in vitro at doses of 50 to 250 g/ml, and they significantly reduced the amounts of intracellular Salmonella (0.53 log) and Listeria (3.16 log), thereby suggesting effective transport into the cells.Gentamicin is an aminoglycoside with antimicrobial activity against Gram-positive and Gram-negative bacteria (3). Its efficacy against these bacteria is established, yet its poor cell membrane permeability limits its clinical use, particularly against intracellular bacterial infections (4). We previously reported core-shell nanostructures encapsulating gentamicin that had poly(sodium acry-with PEO-b-PPO-b-PEO amphiphilic shells and block lengths of ϳ3,600, 1,800, and 3,600 g/mole, respectively (designated ϳ3600-b-1800-b-3600 g/mole) (from Pluronic F68) (8). PAA Ϫϩ Na homopolymers were also incorporated into the nanostructure cores to increase their sizes and charge, thus facilitating high loadings of the polycationic gentamicin in the cores. The stabilities of those nanostructures in the presence of phosphate salts, however, were relatively poor. In the present study, we aimed to improve the stability of the nanostructures in physiological media to enhance delivery of gentamicin into macrophages. The strategy was to incorporate a higher-molecular-weight hydrophobic PPO in the shells, and more PPO relative to the hydrophilic PEO, so that enhanced hydrophobic interactions would contribute to their stabilities in physiological media. Thus, a PAANa copolymer (nonionic portion derived from Pluronic P85) with block lengths of 2160-b-1100-b-2300-b-1100-b-2160 g/mole was blended with a hydrophilic PEO-b-PAA Ϫϩ Na copolymer with block lengths of 2000-b-7200 g/mole, and these copolymers were condensed with gentamicin to afford core-shell nanostructures. These nanostructures were investigated in vitro to establish transport into the macrophages and determine their activities against vacuolar Salmonella and cytoplasm-resident Listeria (1, 11).A scheme for preparing the nanostructures is shown in Fig. 1. PAA Ϫϩ Na-b-PEO-b-PPO-b-PEO-b-PAA Ϫϩ Na (25 mg; 1.7 ϫ 10 Ϫ4 equivalents [eq] of carboxylates) and PEO-b-PAA Ϫϩ Na (25 mg; 2.7 ϫ 10 Ϫ4 eq of carboxylates) were dissolved in 25 ml of phosphate-buffered saline (PBS). The solution was sonicated while 5 ml of gentamicin sulfate solution (13.3 mg ml Ϫ1 gentamicin sulfate, equal to 40 mg gentamicin; 4.2 ϫ 10 Ϫ4 eq of cations) was added to form a turbid dispersion of nanostructures in PBS. Dynamic light scattering (DLS; Malvern Zetasizer NanoZS particle analyzer; Malvern Instruments, Ltd., Malvern, United Kingdom) at 37 Ϯ 0.1°C and pH 7.4 in PBS showed a monomodal peak with an intensity average diameter...