| 1. |
- Asad, Shno, et al.
(författare)
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Proteomics-Informed Identification of Luminal Targets For In Situ Diagnosis of Inflammatory Bowel Disease
- 2021
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Ingår i: Journal of Pharmaceutical Sciences. - : Elsevier. - 0022-3549 .- 1520-6017. ; 110:1, s. 239-250
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Tidskriftsartikel (refereegranskat)abstract
- Inflammatory bowel disease (IBD) is a chronic condition resulting in impaired intestinal homeostasis. Current practices for diagnosis of IBD are challenged by invasive, demanding procedures. We hypothesized that proteomics analysis could provide a powerful tool for identifying clinical biomarkers for non-invasive IBD diagnosis. Here, the global intestinal proteomes from commonly used in vitro and in vivo models of IBD were analyzed to identify apical and luminal proteins that can be targeted by orally delivered diagnostic agents. Global proteomics analysis revealed upregulated plasma membrane proteins in intestinal segments of proximal- and distal colon from dextran sulfate sodium-treated mice and also in inflamed human intestinal Caco-2 cells pretreated with pro-inflammatory agents. The upregulated colon proteins in mice were compared to the proteome of the healthy ileum, to ensure targeting of diagnostic agents to the inflamed colon. Promising target proteins for future investigations of non-invasive diagnosis of IBD were found in both systems and included Tgm2/TGM2, Icam1/ICAM1, Ceacam1/CEACAM1, and Anxa1/ANXA1. Ultimately, these findings will guide the selection of appropriate antibodies for surface functionalization of imaging agents aimed to target inflammatory biomarkers in situ.
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| 2. |
- Hempel, Nele-Johanna, et al.
(författare)
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Utilizing Laser Activation of Photothermal Plasmonic Nanoparticles to Induce On-Demand Drug Amorphization inside a Tablet
- 2021
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Ingår i: Molecular Pharmaceutics. - : American Chemical Society (ACS). - 1543-8384 .- 1543-8392. ; 18:6, s. 2254-2262
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Tidskriftsartikel (refereegranskat)abstract
- Poor aqueous drug solubility represents a major challenge in oral drug delivery. A novel approach to overcome this challenge is drug amorphization inside a tablet, that is, on-demand drug amorphization. The amorphous form is a thermodynamically instable, disordered solid-state with increased dissolution rate and solubility compared to its crystalline counterpart. During on-demand drug amorphization, the drug molecularly disperses into a polymer to form an amorphous solid at elevated temperatures inside a tablet. This study investigates, for the first time, the utilization of photothermal plasmonic nanoparticles for on-demand drug amorphization as a new pharmaceutical application. For this, near-IR photothermal plasmonic nanoparticles were tableted together with a crystalline drug (celecoxib) and a polymer (polyvinylpyrrolidone). The tablets were subjected to a near-IR laser at different intensities and durations to study the rate of drug amorphization under each condition. During laser irradiation, the plasmonic nanoparticles homogeneously heated the tablet. The temperature was directly related to the rate and degree of amorphization. Exposure times as low as 180 s at 1.12 W cm(-2) laser intensity with only 0.25 wt % plasmonic nanoparticles and up to 50 wt % drug load resulted in complete drug amorphization. Therefore, near-IR photothermal plasmonic nanoparticles are promising excipients for on-demand drug amorphization with laser irradiation.
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