Browsing by Subject "Nanostructures"

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    Cerivastatin Nanoliposome as a Potential Disease Modifying Approach for the Treatment of Pulmonary Arterial Hypertension
    (American Society for Pharmacology and Experimental Therapeutics, 2018-07) Lee, Young; Pai, S. Balakrishna; Bellamkonda, Ravi V.; Thompson, David H.; Singh, Jaipal; Department of Medicine, IU School of Medicine
    In this study we investigated nanoliposome as an approach to tailoring the pharmacology of cerivastatin as a disease-modifying drug for pulmonary arterial hypertension (PAH). Cerivastatin encapsulated liposomes with an average diameter of 98 ± 27 nm were generated by a thin film and freeze-thaw process. The nanoliposomes demonstrated sustained drug-release kinetics in vitro and inhibited proliferation of pulmonary artery (PA) smooth muscle cells with significantly less cellular cytotoxicity as compared with free cerivastatin. When delivered by inhalation to a rat model of monocrotaline-induced PAH, cerivastatin significantly reduced PA pressure from 55.13 ± 9.82 to 35.56 ± 6.59 mm Hg (P < 0.001) and diminished PA wall thickening. Echocardiography showed that cerivastatin significantly reduced right ventricle thickening (monocrotaline: 0.34 ± 0.02 cm vs. cerivastatin: 0.26 ± 0.02 cm; P < 0.001) and increased PA acceleration time (monocrotaline: 13.98 ± 1.14 milliseconds vs. cerivastatin: 21.07 ± 2.80 milliseconds; P < 0.001). Nanoliposomal cerivastatin was equally effective or slightly better than cerivastatin in reducing PA pressure (monocrotaline: 67.06 ± 13.64 mm Hg; cerivastatin: 46.31 ± 7.64 mm Hg vs. liposomal cerivastatin: 37.32 ± 9.50 mm Hg) and improving parameters of right ventricular function as measured by increasing PA acceleration time (monocrotaline: 24.68 ± 3.92 milliseconds; cerivastatin: 32.59 ± 6.10 milliseconds vs. liposomal cerivastatin: 34.96 ± 7.51 milliseconds). More importantly, the rate and magnitude of toxic cerivastatin metabolite lactone generation from the intratracheally administered nanoliposomes was significantly lower as compared with intravenously administered free cerivastatin. These studies show that nanoliposome encapsulation improved in vitro and in vivo pharmacologic and safety profile of cerivastatin and may represent a safer approach as a disease-modifying therapy for PAH.
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    Enhancing the speed of DNA walkers through soft confinement
    (Springer Nature, 2025-03-19) Ogieva, Mathew O.; Pfeifer, Wolfgang G.; Sensale, Sebastian; Physics, School of Science
    Over the past two decades, dynamic DNA origami structures have emerged as promising candidates for nanoscale signal and cargo transport. DNA walkers, programmable nanostructures that traverse tracks made of DNA, represent a key innovation in this field, enabling controlled and directional movement at the nanoscale. Despite relatively fast diffusion rates, the speed of DNA walkers remains constrained by the reaction-limited nature of strand exchange mechanisms, which depend both on the foothold-walker affinity and on the probability of the molecules being found close enough to bind. In this study, we explore how spatial confinement can expedite walker motion and evaluate two strategies to achieve this: the introduction of tailed DNA footholds, promoting pseudo-rotational dynamics, and the addition of walls along the DNA track, promoting pseudo-curvilinear dynamics. Using simulations and stochastic theories, we demonstrate that, by reducing the sampling of conformations far from the binding sites, tailed footholds provide the best speed enhancement, achieving a fourfold increase in speed. Trench-like confinement yields a more modest threefold increase, what, while significant, requires extensive structural modifications to the DNA track, limiting design flexibility and reducing cost-efficiency in comparison to the tailed footholds. The combination of tailed footholds and trench-like confinement turns the walker-foothold system bistable, with two distinct stable states separated by an energy barrier. By focusing on the properties of the DNA track, this study offers novel insights into leveraging soft structural motifs to optimize signal propagation rates, with implications for sensing, robotics and molecular computing in reaction-diffusion systems.