118 research outputs found

    Hierarchical structured and programmed vehicles deliver drugs locally to inflamed sites of intestine

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    Orally administrable drug delivery vehicles are developed to manage incurable inflammatory bowel disease (IBD), however, their therapeutic outcomes are compromised by the side effects of systemic drug exposure. Herein, we use hyaluronic acid functionalized porous silicon nanoparticle to bridge enzyme-responsive hydrogel and pH-responsive polymer, generating a hierarchical structured (nano-in-nano-in-micro) vehicle with programmed properties to fully and sequentially overcome the multiple obstacles for efficiently delivering drugs locally to inflamed sites of intestine. After oral administration, the pH-responsive matrix protects the embedded hybrid nanoparticles containing drug loaded hydrogels against the spatially variable physiological environments of the gastrointestinal tract until they reach the inflamed sites of intestine, preventing premature drug release. The negatively charged hybrid nanoparticles selectively target the inflamed sites of intestine, and gradually release drug in response to the microenvironment of inflamed intestine. Overall, the developed hierarchical structured and programmed vehicles load, protect, transport and release drugs locally to inflamed sites of intestine, contributing to superior therapeutic outcomes. Such strategy could also inspire the development of numerous hierarchical structured vehicles by other porous nanoparticles and stimuli-responsive materials for the local delivery of various drugs to treat plenty of inflammatory gastrointestinal diseases, including IBD, gastrointestinal cancers and viral infections.Peer reviewe

    Fabrication and Characterization of Drug-Loaded Conductive Poly(glycerol sebacate)/Nanoparticle-Based Composite Patch for Myocardial Infarction Applications

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    Heart tissue engineering is critical in the treatment of myocardial infarction, which may benefit from drug-releasing smart materials. In this study, we load a small molecule (3i-1000) in new biodegradable and conductive patches for application in infarcted myocardium. The composite patches consist of a biocompatible elastomer, poly(glycerol sebacate) (PGS), coupled with collagen type I, used to promote cell attachment. In addition, polypyrrole is incorporated because of its electrical conductivity and to induce cell signaling. Results from the in vitro experiments indicate a high density of cardiac myoblast cells attached on the patches, which stay viable for at least 1 month. The degradation of the patches does not show any cytotoxic effect, while 3i-1000 delivery induces cell proliferation. Conductive patches show high blood wettability and drug release, correlating with the rate of degradation of the PGS matrix. Together with the electrical conductivity and elongation characteristics, the developed biomaterial fits the mechanical, conductive, and biological demands required for cardiac treatment.</p

    Multifunctional Biomimetic Nanovaccines Based on Photothermal and Weak-Immunostimulatory Nanoparticulate Cores for the Immunotherapy of Solid Tumors

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    An alternative strategy of choosing photothermal and weak-immunostimulatory porous silicon@Au nanocomposites as particulate cores to prepare a biomimetic nanovaccine is reported to improve its biosafety and immunotherapeutic efficacy for solid tumors. A quantitative analysis method is used to calculate the loading amount of cancer cell membranes onto porous silicon@Au nanocomposites. Assisted with foreign-body responses, these exogenous nanoparticulate cores with weak immunostimulatory effect can still efficiently deliver cancer cell membranes into dendritic cells to activate them and the downstream antitumor immunity, resulting in no occurrence of solid tumors and the survival of all immunized mice during 55 day observation. In addition, this nanovaccine, as a photothermal therapeutic agent, synergized with additional immunotherapies can significantly inhibit the growth and metastasis of established solid tumors, via the initiation of the antitumor immune responses in the body and the reversion of their immunosuppressive microenvironments. Considering the versatile surface engineering of porous silicon nanoparticles, the strategy developed here is beneficial to construct multifunctional nanovaccines with better biosafety and more diagnosis or therapeutic modalities against the occurrence, recurrence, or metastasis of solid tumors in future clinical practice.Peer reviewe

    Hierarchical structured and programmed vehicles deliver drugs locally to inflamed sites of intestine

    Get PDF
    Orally administrable drug delivery vehicles are developed to manage incurable inflammatory bowel disease (IBD), however, their therapeutic outcomes are compromised by the side effects of systemic drug exposure. Herein, we use hyaluronic acid functionalized porous silicon nanoparticle to bridge enzyme-responsive hydrogel and pH-responsive polymer, generating a hierarchical structured (nano-in-nano-in-micro) vehicle with programmed properties to fully and sequentially overcome the multiple obstacles for efficiently delivering drugs locally to inflamed sites of intestine. After oral administration, the pH-responsive matrix protects the embedded hybrid nanoparticles containing drug loaded hydrogels against the spatially variable physiological environments of the gastrointestinal tract until they reach the inflamed sites of intestine, preventing premature drug release. The negatively charged hybrid nanoparticles selectively target the inflamed sites of intestine, and gradually release drug in response to the microenvironment of inflamed intestine. Overall, the developed hierarchical structured and programmed vehicles load, protect, transport and release drugs locally to inflamed sites of intestine, contributing to superior therapeutic outcomes. Such strategy could also inspire the development of numerous hierarchical structured vehicles by other porous nanoparticles and stimuli-responsive materials for the local delivery of various drugs to treat plenty of inflammatory gastrointestinal diseases, including IBD, gastrointestinal cancers and viral infections.</p

    Multifunctional Biomimetic Nanovaccines Based on Photothermal and Weak-Immunostimulatory Nanoparticulate Cores for the Immunotherapy of Solid Tumors

    Get PDF
    An alternative strategy of choosing photothermal and weak-immunostimulatory porous silicon@Au nanocomposites as particulate cores to prepare a biomimetic nanovaccine is reported to improve its biosafety and immunotherapeutic efficacy for solid tumors. A quantitative analysis method is used to calculate the loading amount of cancer cell membranes onto porous silicon@Au nanocomposites. Assisted with foreign-body responses, these exogenous nanoparticulate cores with weak immunostimulatory effect can still efficiently deliver cancer cell membranes into dendritic cells to activate them and the downstream antitumor immunity, resulting in no occurrence of solid tumors and the survival of all immunized mice during 55 day observation. In addition, this nanovaccine, as a photothermal therapeutic agent, synergized with additional immunotherapies can significantly inhibit the growth and metastasis of established solid tumors, via the initiation of the antitumor immune responses in the body and the reversion of their immunosuppressive microenvironments. Considering the versatile surface engineering of porous silicon nanoparticles, the strategy developed here is beneficial to construct multifunctional nanovaccines with better biosafety and more diagnosis or therapeutic modalities against the occurrence, recurrence, or metastasis of solid tumors in future clinical practice

    Surface Modification of Acetaminophen Particles by Atomic Layer Deposition

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    Organic solid pharmaceutical powders are used for the preparation of various drug dosage forms. Primary particles in powder form undergo several processing steps first in pharmaceutical formulations followed by pharmaceutical manufacturing to final dosage form of a drug. These unit operations involve both handling of powders in aqueous or solvent solutions and drying. There will be a probable rise for a demand for the different unit operations in the requirements of protecting the active pharmaceutical ingredient or challenges in powder handling. Besides pharmaceutical manufacturing, there are many biological interfaces where control of surface characteristics of pharmaceutical powders can improve the therapeutic response and bioavailability. In this work, we have modified acetaminophen particles with atomic layer deposition (ALD) by conformal nanometer scale coatings in a one-step coating process. According to the results, ALD comprising common chemistries for Al2O3, TiO2 and ZnO is shown to be a promising coating method for solid pharmaceutical powders. Acetaminophen does not undergo degradation during the ALD coating and maintains its stable polymorphic structure. The nanometer scale ALD coating can sustain the drug release. ALD oxide coated acetaminophen particles show different cytocompatibility assessed in in vitro intestinal Caco-2 cells.Peer reviewe

    Deposition of Aluminum-Doped ZnO Films by ICP-Assisted Sputtering

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    Inductively coupled plasma (ICP) assisted DC sputter deposition was used for the deposition of Al-doped ZnO (AZO or ZnO:Al) thin films. With increasing ICP RF power, film properties including deposition rate, crystallinity, transparency, and resistivity were improved. To understand the plasma-surface interaction, several plasma diagnostics were performed. Heat fluxes to the substrate were measured by thermal probes, number densities of sputtered metallic atom species were measured by absorption spectroscopy using hollow cathode lamps (HCL) and light emitting diodes (LEDs), and neutral gas temperatures were measured by external cavity diode laser (ECDL) absorption spectroscopy. As a result, it was revealed that the high-density ICP heated the substrate through a high heat flux to the substrate, resulting in a high-quality film deposition without the need for intentional substrate heating. The heat flux to the substrate was predominantly contributed by the plasma charged species, not by the neutral Ar atoms which were also significantly heated in the ICP. The substrate position where the highest quality films were obtained was found to coincide with the position where the substrate heat flux took the maximum value

    Study of the influence of the dielectric composition of Al/Ti/ZrO2:Al2O3/TiN/Si/Al structures on the resistive switching behavior for memory applications

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    The memory behavior of Al/Ti/ZrO2:Al2O3/TiN/Si/Al devices is investigated in this work. They are adequate to be used as resistive switching memories, with two clearly different states. Besides, intermediate states are also accessible in a controllable manner. The electrical characterization in terms of admittance parameters provides relevant complementary information. The cation ratio influences the memory maps and can be changed to obtain specifically sized shape of the maps. © The Electrochemical Society.Peer reviewe
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