cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.5281/zenodo.6954141
title: Assessing methods for representing soil heterogeneity through a flexible approach within the Joint UK Land Environment Simulator (JULES) at version 3.4.1

description: This is the JULES input and output data and plotting scripts used in the paper titled "Assessing methods for representing soil heterogeneity through a flexible approach within the Joint UK Land Environment Simulator (JULES) at version 3.4.1. The tar file contains the following: outputs/cardwfdei_gl4_uncompressed.mon.nc<br> outputs/cardwfdei_gl4_surf_ft_dom_soil.mon.nc<br> outputs/cardwfdei_gl4_gb_dom_soil_decompr_loam.mon.nc<br> outputs/cardwfdei_gl4_surf-soil_consolidated.mon.nc<br> outputs/cardwfdei_gl4_gb_dom_soil_compr_loam.mon.nc<br> plotting_scripts/utils.py<br> plotting_scripts/gb_flux_summary.py<br> plotting_scripts/tile_fsmc_summary.py<br> plotting_scripts/gb_smcl_closure_summary.py<br> plotting_scripts/colors_names.py<br> inputs/drive-file-WFDEI-79-10.txt<br> inputs/WFDEI_data/README.txt<br> inputs/extract_cardwfdei_point.py uncompressed is the output for experiment HResTex.<br> surf_ft_dom_soil is the output for experiment SurfDom.<br> gb_dom_soil_decompr_loam is the output for experiment SurfGB.<br> surf-soil_consolidated is the output for experiment HResTexAgg.<br> gb_dom_soil_compr_loam is the output for experiment DC. Descriptions about the individual plotting scripts are given within each file. The WFDEI data is freely available from a separate source and inputs/WFDEI_data/README.txt describes how to obtain this dataset. inputs/extract_cardwfdei_point.py extracts the WFDEI data for the single latitude/longitude point used in this paper. inputs/drive-file-WFDEI-79-10.txt is the input file required by JULES to read in the WFDEI driving data files.
DOI: 10.4119/unibi/2964834
title: Dataset for: "New way to resum the lattice QCD Taylor series equation of state at finite chemical potential"

description: Datapublication to reproduce all figure in ""New way to resum the lattice QCD Taylor series equation of state at finite chemical potential", accepted for publication in Phys. Rev. D, [arXiv: 2205.08517](https://arxiv.org/abs/2205.08517).
DOI: 10.6084/m9.figshare.4746775
title: Sustained release ivermectin-loaded solid lipid dispersion for subcutaneous delivery: <i>in vitro</i> and <i>in vivo</i> evaluation

description: This work aimed to develop a sustained release solid dispersion of ivermectin (IVM-SD) in a lipid matrix (hydrogenated castor oil, HCO) for subcutaneous delivery. Solvent-melting technology was employed to prepare IVM-SDs using HCO. The physicochemical properties of the IVM-SDs were evaluated by scanning electron microscopy (SEM), X-ray powder diffraction (XRPD), and Fourier transform infrared spectroscopy (FTIR). The release of IVM from IVM-SDs was evaluated with HPLC <i>in vitro.</i> Pharmacokinetics of IVM was studied in rabbits following a single subcutaneous administration of IVM-SD formulations. The efficacy of IVM-SD against the ear mange mite was evaluated in rabbits. IVM was completely dispersed in HCO in an amorphous state at a drug:carrier ratio lower than 1:3. No chemical interactions between drug and carrier were found besides hydrogen bonding for the amorphous IVM-SDs. The amorphous IVM-SDs formulations exhibited a sustained release of IVM versus physical mixtures (PMs) of IVM and HCO. The drug release decreased as the drug:carrier ratios decreased, and the release kinetics of IVM were controlled via diffusion. Cytotoxicity of IVM-SD to MDCK cells was lower than native IVM. The IVM plasma concentration of SD1:3 remained above 1 ng/mL for 49 d. Higher AUC, MRT, and <i>T</i><sub>max</sub> values were obtained at a SD1:3 relative to the IVM group. The IVM-SD improved almost 1.1-fold bioavailability of drug compared with IVM in rabbits. IVM-SD could provide longer persistence against rabbit’s ear mites than a commercial IVM injection. This study shows that these solid lipid dispersions are a promising approach for the development of subcutaneous IVM formulations.
DOI: 10.6084/m9.figshare.4746775.v1
title: Sustained release ivermectin-loaded solid lipid dispersion for subcutaneous delivery: <i>in vitro</i> and <i>in vivo</i> evaluation

description: This work aimed to develop a sustained release solid dispersion of ivermectin (IVM-SD) in a lipid matrix (hydrogenated castor oil, HCO) for subcutaneous delivery. Solvent-melting technology was employed to prepare IVM-SDs using HCO. The physicochemical properties of the IVM-SDs were evaluated by scanning electron microscopy (SEM), X-ray powder diffraction (XRPD), and Fourier transform infrared spectroscopy (FTIR). The release of IVM from IVM-SDs was evaluated with HPLC <i>in vitro.</i> Pharmacokinetics of IVM was studied in rabbits following a single subcutaneous administration of IVM-SD formulations. The efficacy of IVM-SD against the ear mange mite was evaluated in rabbits. IVM was completely dispersed in HCO in an amorphous state at a drug:carrier ratio lower than 1:3. No chemical interactions between drug and carrier were found besides hydrogen bonding for the amorphous IVM-SDs. The amorphous IVM-SDs formulations exhibited a sustained release of IVM versus physical mixtures (PMs) of IVM and HCO. The drug release decreased as the drug:carrier ratios decreased, and the release kinetics of IVM were controlled via diffusion. Cytotoxicity of IVM-SD to MDCK cells was lower than native IVM. The IVM plasma concentration of SD1:3 remained above 1 ng/mL for 49 d. Higher AUC, MRT, and <i>T</i><sub>max</sub> values were obtained at a SD1:3 relative to the IVM group. The IVM-SD improved almost 1.1-fold bioavailability of drug compared with IVM in rabbits. IVM-SD could provide longer persistence against rabbit’s ear mites than a commercial IVM injection. This study shows that these solid lipid dispersions are a promising approach for the development of subcutaneous IVM formulations.
DOI: 10.6084/m9.figshare.5350375.v3
title: Novel reverse electrodialysis-driven iontophoretic system for topical and transdermal delivery of poorly permeable therapeutic agents

description: Topical and transdermal drug delivery has great potential in non-invasive and non-oral administration of poorly bioavailable therapeutic agents. However, due to the barrier function of the stratum corneum, the drugs that can be clinically feasible candidates for topical and transdermal delivery have been limited to small-sized lipophilic molecules. Previously, we fabricated a novel iontophoretic system using reverse electrodialysis (RED) technology (RED system). However, no study has demonstrated its utility in topical and/or transdermal delivery of poorly permeable therapeutic agents. In this study, we report the topical delivery of fluorescein isothiocyanate (FITC)–hyaluronic acid (FITC–HA) and vitamin C and the transdermal delivery of lopinavir using our newly developed RED system in the <i>in vitro</i> hairless mouse skin and <i>in vivo</i> Sprague–Dawley rat models. The RED system significantly enhanced the efficiency of topical HA and vitamin C and transdermal lopinavir delivery. Moreover, the efficiency and safety of transdermal delivery using the RED system were comparable with those of a commercial ketoprofen patch formulation. Thus, the RED system can be a potential topical and transdermal delivery system for various poorly bioavailable pharmaceuticals including HA, vitamin C, and lopinavir.
DOI: 10.6084/m9.figshare.5350375
title: Novel reverse electrodialysis-driven iontophoretic system for topical and transdermal delivery of poorly permeable therapeutic agents

description: Topical and transdermal drug delivery has great potential in non-invasive and non-oral administration of poorly bioavailable therapeutic agents. However, due to the barrier function of the stratum corneum, the drugs that can be clinically feasible candidates for topical and transdermal delivery have been limited to small-sized lipophilic molecules. Previously, we fabricated a novel iontophoretic system using reverse electrodialysis (RED) technology (RED system). However, no study has demonstrated its utility in topical and/or transdermal delivery of poorly permeable therapeutic agents. In this study, we report the topical delivery of fluorescein isothiocyanate (FITC)–hyaluronic acid (FITC–HA) and vitamin C and the transdermal delivery of lopinavir using our newly developed RED system in the <i>in vitro</i> hairless mouse skin and <i>in vivo</i> Sprague–Dawley rat models. The RED system significantly enhanced the efficiency of topical HA and vitamin C and transdermal lopinavir delivery. Moreover, the efficiency and safety of transdermal delivery using the RED system were comparable with those of a commercial ketoprofen patch formulation. Thus, the RED system can be a potential topical and transdermal delivery system for various poorly bioavailable pharmaceuticals including HA, vitamin C, and lopinavir.
DOI: 10.6084/m9.figshare.4811116
title: Enhanced cytotoxic effect of camptothecin nanosponges in anaplastic thyroid cancer cells <i>in vitro</i> and <i>in vivo</i> on orthotopic xenograft tumors

description: Anaplastic carcinoma of the thyroid (ATC) is a lethal human malignant cancer with median survival of 6 months. To date, no treatment has substantially changed its course, which makes urgent need for the development of novel drugs or novel formulations for drug delivery. Nanomedicine has enormous potential to improve the accuracy of cancer therapy by enhancing availability and stability, decreasing effective doses and reducing side effects of drugs. Camptothecin (CPT) is an inhibitor of DNA topoisomerase-I with several anticancer properties but has poor solubility and a high degradation rate. Previously, we reported that CPT encapsulated in β-cyclodextrin-nanosponges (CN-CPT) increased solubility, was protected from degradation and inhibited the growth of prostate tumor cells both <i>in vitro</i> and <i>in vivo</i>. The aim of this study was to extend that work by assessing the CN-CPT effectiveness on ATC both <i>in vitro</i> and <i>in vivo</i>. Results showed that CN-CPT significantly inhibited viability, clonogenic capacity and cell-cycle progression of ATC cell lines showing a faster and enhanced effect compared to free CPT. Moreover, CN-CPT inhibited tumor cell adhesion to vascular endothelial cells, migration, secretion of pro-angiogenic factors (IL-8 and VEGF-α), expression of β-PIX, belonging to the Rho family activators, and phosphorylation of the Erk1/2 MAPK. Finally, CN-CPT significantly inhibited the growth, the metastatization and the vascularization of orthotopic ATC xenografts in SCID/beige mice without apparent toxic effects <i>in vivo</i>. This work extends the previous insight showing that β-cyclodextrin-nanosponges are a promising tool for the treatment of ATC.
DOI: 10.6084/m9.figshare.4811116.v1
title: Enhanced cytotoxic effect of camptothecin nanosponges in anaplastic thyroid cancer cells <i>in vitro</i> and <i>in vivo</i> on orthotopic xenograft tumors

description: Anaplastic carcinoma of the thyroid (ATC) is a lethal human malignant cancer with median survival of 6 months. To date, no treatment has substantially changed its course, which makes urgent need for the development of novel drugs or novel formulations for drug delivery. Nanomedicine has enormous potential to improve the accuracy of cancer therapy by enhancing availability and stability, decreasing effective doses and reducing side effects of drugs. Camptothecin (CPT) is an inhibitor of DNA topoisomerase-I with several anticancer properties but has poor solubility and a high degradation rate. Previously, we reported that CPT encapsulated in β-cyclodextrin-nanosponges (CN-CPT) increased solubility, was protected from degradation and inhibited the growth of prostate tumor cells both <i>in vitro</i> and <i>in vivo</i>. The aim of this study was to extend that work by assessing the CN-CPT effectiveness on ATC both <i>in vitro</i> and <i>in vivo</i>. Results showed that CN-CPT significantly inhibited viability, clonogenic capacity and cell-cycle progression of ATC cell lines showing a faster and enhanced effect compared to free CPT. Moreover, CN-CPT inhibited tumor cell adhesion to vascular endothelial cells, migration, secretion of pro-angiogenic factors (IL-8 and VEGF-α), expression of β-PIX, belonging to the Rho family activators, and phosphorylation of the Erk1/2 MAPK. Finally, CN-CPT significantly inhibited the growth, the metastatization and the vascularization of orthotopic ATC xenografts in SCID/beige mice without apparent toxic effects <i>in vivo</i>. This work extends the previous insight showing that β-cyclodextrin-nanosponges are a promising tool for the treatment of ATC.
DOI: 10.6084/m9.figshare.4616131.v1
title: Asialoglycoprotein receptor targeted delivery of doxorubicin nanoparticles for hepatocellular carcinoma

description: We report asialoglycoprotein receptor (ASGPR)-targeted doxorubicin hydrochloride (Dox) nanoparticles (NPs) for hepatocellular carcinoma (HCC). Polyethylene sebacate (PES)-Gantrez® AN 119 Dox NPs of average size 220 nm with PDI &lt; 0.62 and ∼20% Dox loading were prepared by modified nanoprecipitation. ASGPR ligands, pullulan (Pul), arabinogalactan (AGn), and the combination (Pul-AGn), were anchored by adsorption. Ligand anchoring enabled high liver uptake with a remarkable hepatocyte:nonparenchymal cell ratio of 85:15. Furthermore, Pul-AGn NPs exhibited an additive effect implying incredibly high hepatocyte accumulation. Galactose-mediated competitive inhibition confirmed ASGPR-mediated uptake of ligand-anchored NPs in HepG2 cell lines. Subacute toxicity in rats confirmed the safety of the NP groups. However, histopathological evaluation suggested mild renal toxicity of AGn. Pul NPs revealed sustained reduction in tumor volume in PLC/PRF/5 liver tumor-bearing Nod/Scid mice up to 46 days. Extensive tumor necrosis, reduced collagen content, reduction in the HCC biomarker serum α-fetoprotein (<i>p</i> &lt; 0.05), a mitotic index of 1.135 (day 46), and tumor treated/tumor control (T/C) values of &lt;0.42 signified superior efficacy of Pul NPs. Furthermore, weight gain in the NP groups, and no histopathological alterations indicated that they were well tolerated by the mice. The high efficacy coupled with greater safety portrayed Pul Dox NPs as a promising nanocarrier for improved therapy of HCC.
DOI: 10.6084/m9.figshare.4616131
title: Asialoglycoprotein receptor targeted delivery of doxorubicin nanoparticles for hepatocellular carcinoma

description: We report asialoglycoprotein receptor (ASGPR)-targeted doxorubicin hydrochloride (Dox) nanoparticles (NPs) for hepatocellular carcinoma (HCC). Polyethylene sebacate (PES)-Gantrez® AN 119 Dox NPs of average size 220 nm with PDI &lt; 0.62 and ∼20% Dox loading were prepared by modified nanoprecipitation. ASGPR ligands, pullulan (Pul), arabinogalactan (AGn), and the combination (Pul-AGn), were anchored by adsorption. Ligand anchoring enabled high liver uptake with a remarkable hepatocyte:nonparenchymal cell ratio of 85:15. Furthermore, Pul-AGn NPs exhibited an additive effect implying incredibly high hepatocyte accumulation. Galactose-mediated competitive inhibition confirmed ASGPR-mediated uptake of ligand-anchored NPs in HepG2 cell lines. Subacute toxicity in rats confirmed the safety of the NP groups. However, histopathological evaluation suggested mild renal toxicity of AGn. Pul NPs revealed sustained reduction in tumor volume in PLC/PRF/5 liver tumor-bearing Nod/Scid mice up to 46 days. Extensive tumor necrosis, reduced collagen content, reduction in the HCC biomarker serum α-fetoprotein (<i>p</i> &lt; 0.05), a mitotic index of 1.135 (day 46), and tumor treated/tumor control (T/C) values of &lt;0.42 signified superior efficacy of Pul NPs. Furthermore, weight gain in the NP groups, and no histopathological alterations indicated that they were well tolerated by the mice. The high efficacy coupled with greater safety portrayed Pul Dox NPs as a promising nanocarrier for improved therapy of HCC.
DOI: 10.6084/m9.figshare.5580259.v4
title: A novel lipid prodrug strategy for sustained delivery of hexadecyloxypropyl 9-[2-(phosphonomethoxy)ethyl]guanine (HDP-PMEG) on unwanted ocular proliferation

description: Proliferative vitreoretinopathy (PVR) is a blinding eye disease and there is no effective pharmacological measure to prevent PVR development. The difficulty comes from lack of potent antiproliferative agent and lack of sustained delivery to cover high-risk time window for PVR to develop. Lipid prodrug of PMEG, hexadecyloxypropyl 9-[(2-phosphonomethoxy)ethyl]guanine (HDP-PMEG), was prepared and was evaluated as a pharmacological adjuvant to surgical management of PVR. A dose-escalation study determined that the highest nontoxic dose for intravitreal use in pigmented rabbits was 3 µg per eye. The genotoxicity of HDP-PMEG was harnessed as a perioperative preventative measure against PVR in a rabbit eye model while the sustained intravitreal pharmacological effect was evaluated on a laser-induced fibrovascular model in rat eye. After intravitreal 3 µg, HDP-PMEG particles in the rabbit vitreous was visible for at least 6 weeks. A single 50-min intravitreal infusion of HDP-PMEG demonstrated significant inhibition of PVR formation when compared with the eyes infused with only BSS (BSS vs. HDP-PMEG: estimate = 1.14, OR = 3.1, <i>p</i> = .027). A single intravitreal 104 ng (equivalent to 3 µg for rabbit eye) of HDP-PMEG significantly inhibit laser-induced fibrovascular proliferation in rat eye by 55% (least square mean pixel, BSS = 4763569.5 vs. HDP-PMEG = 2148129.7, <i>p</i> &lt; .0001, generalized estimating equation [GEE]). Retinal fluorescein angiography showed the odds for BSS intervened eyes to have higher-rated FA leaking grades were 38.5 times compared with HDP-PMEG treated eyes (<i>p</i> &lt; .0001, GEE). Our study results indicate that single intravitreal HDP-PMEG may be a promising ocular drug delivery as a perioperative intervention to prevent PVR reoccurrence following primary surgical management.
DOI: 10.6084/m9.figshare.10033304
title: Synergistic effects of a cremophor EL drug delivery system and its U0126 cargo in an <i>ex vivo</i> model

description: Neuroprotection has proven clinically unsuccessful in subarachnoid hemorrhage. We believe that this is because the major component in the early damage pathway, the vascular wall, has not been given the necessary focus. U0126 is a potent inhibitor of vascular phenotypical changes, exemplified by functional endothelin B (ET<sub>B</sub>) receptor upregulation. The current study aimed to determine the optimal dose of U0126 <i>ex vivo</i> and test the toxicology of this dose <i>in vivo</i>. To find the optimal dose and test a suitable <i>in vivo</i> delivery system, we applied an <i>ex vivo</i> model of blood flow cessation and investigated functional ET<sub>B</sub> receptor upregulation (using a specific agonist) as the primary endpoint. The secondary endpoint was depolarization-induced contractility assessed by 60 mM K<sup>+</sup> stimuli. Furthermore, an <i>in vivo</i> toxicology study was performed on the optimal selected doses. U0126 (10 µM) had a strong effect on the prevention of functional ET<sub>B</sub> receptor contractility, combined with minimal effect on the depolarization-induced contractility. When cremophor EL was chosen for drug delivery, it had an inhibitory and additive effect (combined with U0126) on the ET<sub>B</sub> receptor contractility. Hence, 10 µM U0126 in 0.5% cremophor EL seems to be a dose that will be close to the maximal inhibition observed <i>ex vivo</i> on basilar arteries, without exhibiting side effects in the toxicology studies. U0126 and cremophor EL are well tolerated at doses that have effect on ET<sub>B</sub> receptor upregulation. Cremophor EL has an additional positive effect, preventing functional ET<sub>B</sub> receptor upregulation, making it suitable as a drug delivery system.
DOI: 10.6084/m9.figshare.10033304.v1
title: Synergistic effects of a cremophor EL drug delivery system and its U0126 cargo in an <i>ex vivo</i> model

description: Neuroprotection has proven clinically unsuccessful in subarachnoid hemorrhage. We believe that this is because the major component in the early damage pathway, the vascular wall, has not been given the necessary focus. U0126 is a potent inhibitor of vascular phenotypical changes, exemplified by functional endothelin B (ET<sub>B</sub>) receptor upregulation. The current study aimed to determine the optimal dose of U0126 <i>ex vivo</i> and test the toxicology of this dose <i>in vivo</i>. To find the optimal dose and test a suitable <i>in vivo</i> delivery system, we applied an <i>ex vivo</i> model of blood flow cessation and investigated functional ET<sub>B</sub> receptor upregulation (using a specific agonist) as the primary endpoint. The secondary endpoint was depolarization-induced contractility assessed by 60 mM K<sup>+</sup> stimuli. Furthermore, an <i>in vivo</i> toxicology study was performed on the optimal selected doses. U0126 (10 µM) had a strong effect on the prevention of functional ET<sub>B</sub> receptor contractility, combined with minimal effect on the depolarization-induced contractility. When cremophor EL was chosen for drug delivery, it had an inhibitory and additive effect (combined with U0126) on the ET<sub>B</sub> receptor contractility. Hence, 10 µM U0126 in 0.5% cremophor EL seems to be a dose that will be close to the maximal inhibition observed <i>ex vivo</i> on basilar arteries, without exhibiting side effects in the toxicology studies. U0126 and cremophor EL are well tolerated at doses that have effect on ET<sub>B</sub> receptor upregulation. Cremophor EL has an additional positive effect, preventing functional ET<sub>B</sub> receptor upregulation, making it suitable as a drug delivery system.
DOI: 10.6084/m9.figshare.7814099.v1
title: Intra-articular injection of triamcinolone acetonide releasing biomaterial microspheres inhibits pain and inflammation in an acute arthritis model

description: Inflammation of the synovium and joint capsule is a main driver of pain in an osteoarthritic (OA) joint. Triamcinolone acetonide (TAA) is a classical corticosteroid that reduces synovitis and alleviates pain, albeit transiently. Biomaterial-based local TAA release may prolong the suppression of pain without the need for multiple injections. Polylactic-co-glycolic acid (PLGA) formulations of TAA prolong OA pain relief to a limited extent. A novel polyesteramide (PEA) microsphere platform allows for extended release in the OA joint for over 3 months. To evaluate their effect on pain and inflammation, TAA-loaded microspheres were intra-articularly delivered to the knee joint in a rat model of acute arthritis induced by intra-articular injection of streptococcal cell wall peptidoglycan-polysaccharide (PGPS) and subsequent flare-ups by intravenous PGPS injections. PEA-loaded microspheres were benchmarked with TAA-loaded PLGA microspheres and bolus TAA injection. TAA treatments were injected intra-articularly before the first induced flare-up. TAA-loaded PEA and PLGA microspheres reduced joint swelling and signs of pain-like behavior over the entire study period, as assessed by weight bearing and referred mechanical hypersensitivity, whereas bolus suspension was effective for a shorter time period. TAA-loaded PEA microspheres reduced lameness to a greater extent than TAA-loaded PLGA microspheres. In conclusion, a single intra-articular injection of TAA-loaded PEA microspheres reduced joint swelling and induced longer pain relief compared to bolus injection. Hence relief of inflammation and pain by PEA-based delivery of TAA may prove to be effective and durable.