RESUMEN
Antibiotics are used to treat many infectious diseases such as urinary tract infection. However, the resistance to antibiotic can increase due to the high-dose exposure to the human body. Alternative methods to lower the dosage of the antibiotics and deliver it to the specific organ are required for a more effective delivery and treatment at much lower dosage. A stable loading of amoxicillin on purified and polyethyleneimine-functionalized nano diamond particles is used along with magnetic nanoparticles for drug delivery in this study. This novel approach is expected to expand the scope of using nano diamond for targeted drug delivery in which nanodiamond is combined with a ferromagnetic material such as Fe3O4 to deliver a specific drug to a particular site using an external magnetic field. To this end, the synthesis and loading of the amoxicillin on Fe3O4 nanoparticles and combining it with nanodiamond-polyethyleneimine-amoxicillin is investigated in this research. Fe3O4 magnetic nanoparticles of cubic spinel structure are synthesized by microwave-assisted techniques, and different combinations of polyethyleneimine loaded ND and Fe3O4 are studied. It is shown that a structural configuration consisting of the core of magnetic particles with nanodiamond and polyethyleneimine can load 40 mg of amoxicillin and gradually released it in different media. The results on drug loading and release kinetics are studied and discussed in this paper.
Asunto(s)
Nanodiamantes , Polietileneimina , Amoxicilina , Óxido Ferrosoférrico , Humanos , MagnetismoRESUMEN
About 25-44% of women will experience at least one episode of recurrent UTI and the causative agent in over 70% of UTI cases is uropathogenic Escherichia coli (UPEC). UPEC cause recurrent UTI by evading the bladder's innate immune system through internalization into the bladder epithelium where antibiotics cannot reach or be effective. Thus, it is important to develop novel therapeutics to eliminate these intracellular pathogens. Nanodiamonds (NDs) are biocompatible nanomaterials that serve as promising candidates for targeted therapeutic applications. The objective of the current study was to investigate if 6 or 25 nm NDs can kill extracellular and intracellular UPEC in infected bladder cells. We utilized the human bladder epithelial cell line, T24, and an invasive strain of UPEC that causes recurrent UTI. We found that acid-purified 6 nm NDs displayed greater antibacterial properties towards UPEC than 25 nm NDs (11.5% vs 94.2% CFU/mL at 100 µg/mL of 6 and 25 nm, respectively; P<0.001). Furthermore, 6 nm NDs were better than 25 nm NDs in reducing the number of UPEC internalized in T24 bladder cells (46.1% vs 81.1% CFU/mL at 100 µg/mL of 6 and 25 nm, respectively; P<0.01). Our studies demonstrate that 6 nm NDs interacted with T24 bladder cells in a dose-dependent manner and were internalized in 2 hours through an actin-dependent mechanism. Finally, internalization of NDs was required for reducing the number of intracellular UPEC in T24 bladder cells. These findings suggest that 6 nm NDs are promising candidates to treat recurrent UTIs.
Asunto(s)
Nanodiamantes , Infecciones Urinarias/microbiología , Escherichia coli Uropatógena/efectos de los fármacos , Línea Celular , Recuento de Colonia Microbiana , Humanos , Técnicas In Vitro , Microscopía Confocal , Microscopía Electrónica de Transmisión , Espectrometría Raman , Vejiga Urinaria/citología , Vejiga Urinaria/microbiología , Vejiga Urinaria/ultraestructuraRESUMEN
Urinary tract infections (UTIs) cost $0.4-0.5 billion a year in the US and is the second most common disease affecting millions of people. As resistance to antibiotics becomes more common, a greater need for alternative treatments is needed. Nanodiamond particles (NDPs) are actively researched as drug delivery platforms due to their biocompatibility, particle size, and stable inert core. This research is aimed at developing NDPs as antibiotic drug delivery platforms for treating UTIs. To this end, 100 nm, 75 nm, 25 nm and 6 nm size NDPs are purified with acid and heat treatment techniques. Raman spectra of the NDPs showed that the acid treatment method resulted in higher diamond yield. Fourier transform infrared spectroscopy (FTIR) studies showed that both purification techniques result in oxygen terminated surface groups. Efficiency of loading amoxicillin on 25 nm NDPs based on electrostatic interaction of NDPs, functionalizing surfaces of NDPs with hydrogen, and polyethylenimine (PEI) are investigated. It is found that the electrostatic and surface hydrogenation approaches are not efficient in loading amoxicillin on the NDPs. On the other hand, PEI functionalized NDPs produced successful loading with amoxicillin as indicated by the presence of the ß-lactam peak at 1770 cm(-1), amide peak at 1680 cm(-1), and bond between PEI NH stretching and amoxicillin -COOH group at 3650 cm(-1) by the FTIR spectra. These results are expected to lay the foundation for developing NDP based targeted drug delivery treatment techniques for treating UTIs and other infectious diseases.
Asunto(s)
Amoxicilina/química , Antibacterianos/química , Portadores de Fármacos/química , Nanodiamantes/química , Amoxicilina/metabolismo , Antibacterianos/metabolismo , Liberación de Fármacos , Microscopía Electrónica de Rastreo , Tamaño de la Partícula , Polietileneimina/química , Espectroscopía Infrarroja por Transformada de Fourier , Espectrometría Raman , Electricidad Estática , Propiedades de SuperficieRESUMEN
Light induced cis/trans isomerization in the family of merocyanine (MC) dyes offers a recyclable proton pumping ability which can potentially be used in hybrid bio-electronic devices. In this article, a hexadecyl MC dye is embedded in lipid molecules to make a macromolecular configuration of a lipid/hexadecyl MC membrane. Lipid molecules play a critical role in stabilizing the dye in a membrane structure for practical use in energy devices. In this study, we first examined the proton pumping characteristic of the lipid/hexadecyl MC membrane in a conventional photoelectrochemical cell. Next, a major modification in the cell was introduced by eliminating I2/I-electrolyte which resulted in a two-fold increase in the open circuit voltage compared with that of the conventional cell. In addition, the charging time in the new cell was reduced approximately four orders of magnitude. This research demonstrated that the newly designed lipid- MC cell can act as a promising bioelectronic device based on the green energy of photoinduced MC dye proton pumping.
Asunto(s)
Benzopiranos/química , Indoles/química , Lípidos/química , Modelos Químicos , Conformación Molecular , Espectroscopía de Protones por Resonancia Magnética , Difracción de Rayos XRESUMEN
A rapid, environmental friendly and low-cost method to prepare hydroxyapatite nanoparticles is proposed. In this method, hydroxyapatite is produced in a sonicated pseudo-body solution. The sonication time was found effective in the formation of the crystalline phase of nanoparticles. In our experimental condition, 15 min sonication resulted in the most pure hydroxyapatite phase. Also it was shown that growth temperature is a crucial factor and hydroxyapatite crystallizes only at 37 degrees C. The particles formed by sonication were generally smaller and more spherical than those obtained without sonication. Sonication increased the hydroxyapatite crystal growth rate up to 5.5 times compared to non-sonication condition. The comparison between the specific surface area of hydroxyapatite nanoparticles obtained by sonication and without sonication demonstrated that sonication increased the specific surface area from 63 m(2)/g to 107 m(2)/g and decreased the size of nanoparticles from 30 nm to 18 nm. Analysis on the pore structure demonstrated that the fractal structures obtained with and without sonication were considerably different.