cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.14798289.v1
title: Average Nucleotide Identity of 40 Agrobacterium spp.

description: Average Nucleotide Identity of 40 Agrobacterium spp. computed with pyANI
DOI: 10.6084/m9.figshare.7430678
title: Delivery of magnetic micro/nanoparticles and magnetic-based drug/cargo into arterial flow for targeted therapy

description: Magnetic drug targeting (MDT) and magnetic-based drug/cargo delivery are emerging treatment methods which attracting the attention of many researchers for curing different cancers and artery diseases such as atherosclerosis. Herein, computational studies are accomplished by utilizing magnetic approaches for cancer and artery atherosclerosis drug delivery, including nanomagnetic drug delivery and magnetic-based drug/cargo delivery. For the first time, the four-layer structural model of the artery tissue and its porosity parameters are modeled in this study which enables the interaction of particles with the tissue walls in blood flow. The effects of parameters, including magnetic field strength (MFS), magnet size, particle size, the initial position of particles, and the relative magnetic permeability of particles, on the efficacy of MDT through the artery walls are characterized. The magnetic particle penetration into artery layers and fibrous cap (the covering layer over the inflamed part of the artery) is further simulated. The MDT in healthy and diseased arteries demonstrates that some of the particles stuck in these tissues due to the collision of particles or blood flow deviation in the vicinity of the inflamed part of the artery. Therefore the geometry of artery and porosity of its layers should be considered to show the real interaction of particles with the artery walls. Also, the results show that increasing the particles/drug/cargo size and MFS leads to more particles/drug/cargo retention within the tissue. The present work provides insights into the decisive factors in arterial MDT with an obvious impact on locoregional cancer treatment, tissue engineering, and regenerative medicine.
DOI: 10.6084/m9.figshare.7430678.v1
title: Delivery of magnetic micro/nanoparticles and magnetic-based drug/cargo into arterial flow for targeted therapy

description: Magnetic drug targeting (MDT) and magnetic-based drug/cargo delivery are emerging treatment methods which attracting the attention of many researchers for curing different cancers and artery diseases such as atherosclerosis. Herein, computational studies are accomplished by utilizing magnetic approaches for cancer and artery atherosclerosis drug delivery, including nanomagnetic drug delivery and magnetic-based drug/cargo delivery. For the first time, the four-layer structural model of the artery tissue and its porosity parameters are modeled in this study which enables the interaction of particles with the tissue walls in blood flow. The effects of parameters, including magnetic field strength (MFS), magnet size, particle size, the initial position of particles, and the relative magnetic permeability of particles, on the efficacy of MDT through the artery walls are characterized. The magnetic particle penetration into artery layers and fibrous cap (the covering layer over the inflamed part of the artery) is further simulated. The MDT in healthy and diseased arteries demonstrates that some of the particles stuck in these tissues due to the collision of particles or blood flow deviation in the vicinity of the inflamed part of the artery. Therefore the geometry of artery and porosity of its layers should be considered to show the real interaction of particles with the artery walls. Also, the results show that increasing the particles/drug/cargo size and MFS leads to more particles/drug/cargo retention within the tissue. The present work provides insights into the decisive factors in arterial MDT with an obvious impact on locoregional cancer treatment, tissue engineering, and regenerative medicine.
DOI: 10.6084/m9.figshare.7258487
title: Development and characterization of sorafenib-loaded lipid nanocapsules for the treatment of glioblastoma

description: Anticancer agents that target both tumor cells and angiogenesis are of potential interest for glioblastoma (GB) therapy. One such agent is sorafenib (SFN), a tyrosine kinase inhibitor. However, poor aqueous solubility and undesirable side effects limit its clinical application, including local treatment. We encapsulated SFN in lipid nanocapsules (LNCs) to overcome these drawbacks. LNCs are nanocarriers formulated according to a solvent-free process, using only components that have received regulatory approval. SFN-LNCs had a diameter of 54 ± 1 nm, high encapsulation efficiency (&gt;90%), and a drug payload of 2.11 ± 0.03 mg/g of LNC dispersion. They inhibited <i>in vitro</i> angiogenesis and decreased human U87MG GB cell viability similarly to free SFN. <i>In vivo</i> studies showed that the intratumoral administration of SFN-LNCs or free SFN in nude mice bearing an orthotopic U87MG human GB xenograft decreased the proportion of proliferating cells in the tumor relative to control groups. SFN-LNCs were more effective than free SFN for inducing early tumor vascular normalization, characterized by increases in tumor blood flow and decreases in tumor vessel area. These results highlight the potential of LNCs as delivery systems for SFN. The vascular normalization induced by SFN-LNCs could be used to improve the efficacy of chemotherapy or radiotherapy for treating GB.
DOI: 10.6084/m9.figshare.7258487.v2
title: Development and characterization of sorafenib-loaded lipid nanocapsules for the treatment of glioblastoma

description: Anticancer agents that target both tumor cells and angiogenesis are of potential interest for glioblastoma (GB) therapy. One such agent is sorafenib (SFN), a tyrosine kinase inhibitor. However, poor aqueous solubility and undesirable side effects limit its clinical application, including local treatment. We encapsulated SFN in lipid nanocapsules (LNCs) to overcome these drawbacks. LNCs are nanocarriers formulated according to a solvent-free process, using only components that have received regulatory approval. SFN-LNCs had a diameter of 54 ± 1 nm, high encapsulation efficiency (&gt;90%), and a drug payload of 2.11 ± 0.03 mg/g of LNC dispersion. They inhibited <i>in vitro</i> angiogenesis and decreased human U87MG GB cell viability similarly to free SFN. <i>In vivo</i> studies showed that the intratumoral administration of SFN-LNCs or free SFN in nude mice bearing an orthotopic U87MG human GB xenograft decreased the proportion of proliferating cells in the tumor relative to control groups. SFN-LNCs were more effective than free SFN for inducing early tumor vascular normalization, characterized by increases in tumor blood flow and decreases in tumor vessel area. These results highlight the potential of LNCs as delivery systems for SFN. The vascular normalization induced by SFN-LNCs could be used to improve the efficacy of chemotherapy or radiotherapy for treating GB.
DOI: 10.6084/m9.figshare.6445478.v1
title: Development of a docetaxel micellar formulation using poly(ethylene glycol)–polylactide–poly(ethylene glycol) (PEG–PLA–PEG) with successful reconstitution for tumor targeted drug delivery

description: Docetaxel (DTX)-loaded polymeric micelles (DTBM) were formulated using the triblock copolymer, poly(ethylene glycol)–polylactide–poly(ethylene glycol) (PEG–PLA–PEG), to comprehensively study their pharmaceutical application as anticancer nanomedicine. DTBM showed a stable formulation of anticancer nanomedicine that could be reconstituted after lyophilization (DTBM-R) in the presence of PEG 2000 and D-mannitol (Man) as surfactant and protectant, respectively. DTBM-R showed a particle size less than 150 nm and greater than 90% of DTX recovery after reconstitution. The robustly formed micelles might minimize systemic toxicity due to their sustained drug release and also maximize antitumor efficacy through increased accumulation and release of DTX from the micelles. From the pharmaceutical development point of view, DTBM-R showing successful reconstitution could be considered as a potent nanomedicine for tumor treatment.
DOI: 10.6084/m9.figshare.6445478
title: Development of a docetaxel micellar formulation using poly(ethylene glycol)–polylactide–poly(ethylene glycol) (PEG–PLA–PEG) with successful reconstitution for tumor targeted drug delivery

description: Docetaxel (DTX)-loaded polymeric micelles (DTBM) were formulated using the triblock copolymer, poly(ethylene glycol)–polylactide–poly(ethylene glycol) (PEG–PLA–PEG), to comprehensively study their pharmaceutical application as anticancer nanomedicine. DTBM showed a stable formulation of anticancer nanomedicine that could be reconstituted after lyophilization (DTBM-R) in the presence of PEG 2000 and D-mannitol (Man) as surfactant and protectant, respectively. DTBM-R showed a particle size less than 150 nm and greater than 90% of DTX recovery after reconstitution. The robustly formed micelles might minimize systemic toxicity due to their sustained drug release and also maximize antitumor efficacy through increased accumulation and release of DTX from the micelles. From the pharmaceutical development point of view, DTBM-R showing successful reconstitution could be considered as a potent nanomedicine for tumor treatment.
DOI: 10.6084/m9.figshare.6860339
title: Intravenous delivery of a liposomal formulation of voriconazole improves drug pharmacokinetics, tissue distribution, and enhances antifungal activity

description: Voriconazole (VCZ), a triazole with a large spectrum of action is one of the most recommended antifungal agents as the first line therapy against several clinically important systemic fungal infections, including those by <i>Candida albicans</i>. This antifungal has moderate water solubility and exhibits a nonlinear pharmacokinetic (PK) profile. By entrapping VCZ into liposomes, it is possible to circumvent certain downsides of the currently available product such as a reduction in the rate of its metabolization into an inactive form, avoidance of the toxicity of the sulfobutyl ether-beta-cyclodextrin (SBECD), vehicle used to increase its solubility. PKs and biodistribution of VCZ modified by encapsulation into liposomes resulted in improved antifungal activity, due to increased specificity and tissue penetration. In this work, liposomal VCZ resulted in AUC<sub>0–24</sub>/MIC ratio of 53.51 ± 11.12, whereas VFEND<sup>®</sup> resulted in a 2.5-fold lower AUC<sub>0–24</sub>/MIC ratio (21.51 ± 2.88), indicating favorable antimicrobial systemic activity. VCZ accumulation in the liver and kidneys was significantly higher when the liposomal form was used. Protection of the drug from biological degradation and reduced rate of metabolism leads to a 30% reduction of AUC of the inactive metabolite voriconazole-N-oxide (VNO) when the liposomal drug was administered. Liposomal VCZ presents an alternative therapeutic platform, leading to a safe and effective treatment against systemic fungal infections.
DOI: 10.6084/m9.figshare.6860339.v2
title: Intravenous delivery of a liposomal formulation of voriconazole improves drug pharmacokinetics, tissue distribution, and enhances antifungal activity

description: Voriconazole (VCZ), a triazole with a large spectrum of action is one of the most recommended antifungal agents as the first line therapy against several clinically important systemic fungal infections, including those by <i>Candida albicans</i>. This antifungal has moderate water solubility and exhibits a nonlinear pharmacokinetic (PK) profile. By entrapping VCZ into liposomes, it is possible to circumvent certain downsides of the currently available product such as a reduction in the rate of its metabolization into an inactive form, avoidance of the toxicity of the sulfobutyl ether-beta-cyclodextrin (SBECD), vehicle used to increase its solubility. PKs and biodistribution of VCZ modified by encapsulation into liposomes resulted in improved antifungal activity, due to increased specificity and tissue penetration. In this work, liposomal VCZ resulted in AUC<sub>0–24</sub>/MIC ratio of 53.51 ± 11.12, whereas VFEND<sup>®</sup> resulted in a 2.5-fold lower AUC<sub>0–24</sub>/MIC ratio (21.51 ± 2.88), indicating favorable antimicrobial systemic activity. VCZ accumulation in the liver and kidneys was significantly higher when the liposomal form was used. Protection of the drug from biological degradation and reduced rate of metabolism leads to a 30% reduction of AUC of the inactive metabolite voriconazole-N-oxide (VNO) when the liposomal drug was administered. Liposomal VCZ presents an alternative therapeutic platform, leading to a safe and effective treatment against systemic fungal infections.
DOI: 10.6084/m9.figshare.6860339.v1
title: Intravenous delivery of a liposomal formulation of voriconazole improves drug pharmacokinetics, tissue distribution, and enhances antifungal activity

description: Voriconazole (VCZ), a triazole with a large spectrum of action is one of the most recommended antifungal agents as the first line therapy against several clinically important systemic fungal infections, including those by <i>Candida albicans</i>. This antifungal has moderate water solubility and exhibits a nonlinear pharmacokinetic (PK) profile. By entrapping VCZ into liposomes, it is possible to circumvent certain downsides of the currently available product such as a reduction in the rate of its metabolization into an inactive form, avoidance of the toxicity of the sulfobutyl ether-beta-cyclodextrin (SBECD), vehicle used to increase its solubility. PKs and biodistribution of VCZ modified by encapsulation into liposomes resulted in improved antifungal activity, due to increased specificity and tissue penetration. In this work, liposomal VCZ resulted in AUC<sub>0–24</sub>/MIC ratio of 53.51 ± 11.12, whereas VFEND<sup>®</sup> resulted in a 2.5-fold lower AUC<sub>0–24</sub>/MIC ratio (21.51 ± 2.88), indicating favorable antimicrobial systemic activity. VCZ accumulation in the liver and kidneys was significantly higher when the liposomal form was used. Protection of the drug from biological degradation and reduced rate of metabolism leads to a 30% reduction of AUC of the inactive metabolite voriconazole-N-oxide (VNO) when the liposomal drug was administered. Liposomal VCZ presents an alternative therapeutic platform, leading to a safe and effective treatment against systemic fungal infections.
DOI: 10.6084/m9.figshare.6291044.v2
title: Inhalation delivery of topotecan is superior to intravenous exposure for suppressing lung cancer in a preclinical model

description: Intravenous (IV) topotecan is approved for the treatment of various malignancies including lung cancer but its clinical use is greatly undermined by severe hematopoietic toxicity. We hypothesized that inhalation delivery of topotecan would increase local exposure and efficacy against lung cancer while reducing systemic exposure and toxicity. These hypotheses were tested in a preclinical setting using a novel inhalable formulation of topotecan against the standard IV dose. Respirable dry-powder of topotecan was manufactured through spray-drying technology and the pharmacokinetics of 0.14 and 0.79 mg/kg inhalation doses were compared with 0.7 mg/kg IV dose. The efficacy of four weekly treatments with 1 mg/kg inhaled vs. 2 mg/kg IV topotecan were compared to untreated control using an established orthotopic lung cancer model for a fast (H1975) and moderately growing (A549) human lung tumors in the nude rat. Inhalation delivery increased topotecan exposure of lung tissue by approximately 30-fold, lung and plasma half-life by 5- and 4-folds, respectively, and reduced the maximum plasma concentration by 2-fold than the comparable IV dose. Inhaled topotecan improved the survival of rats with the fast-growing lung tumors from 7 to 80% and reduced the tumor burden of the moderately-growing lung tumors over 5- and 10-folds, respectively, than the 2-times higher IV topotecan and untreated control (<i>p</i>
DOI: 10.6084/m9.figshare.6291044
title: Inhalation delivery of topotecan is superior to intravenous exposure for suppressing lung cancer in a preclinical model

description: Intravenous (IV) topotecan is approved for the treatment of various malignancies including lung cancer but its clinical use is greatly undermined by severe hematopoietic toxicity. We hypothesized that inhalation delivery of topotecan would increase local exposure and efficacy against lung cancer while reducing systemic exposure and toxicity. These hypotheses were tested in a preclinical setting using a novel inhalable formulation of topotecan against the standard IV dose. Respirable dry-powder of topotecan was manufactured through spray-drying technology and the pharmacokinetics of 0.14 and 0.79 mg/kg inhalation doses were compared with 0.7 mg/kg IV dose. The efficacy of four weekly treatments with 1 mg/kg inhaled vs. 2 mg/kg IV topotecan were compared to untreated control using an established orthotopic lung cancer model for a fast (H1975) and moderately growing (A549) human lung tumors in the nude rat. Inhalation delivery increased topotecan exposure of lung tissue by approximately 30-fold, lung and plasma half-life by 5- and 4-folds, respectively, and reduced the maximum plasma concentration by 2-fold than the comparable IV dose. Inhaled topotecan improved the survival of rats with the fast-growing lung tumors from 7 to 80% and reduced the tumor burden of the moderately-growing lung tumors over 5- and 10-folds, respectively, than the 2-times higher IV topotecan and untreated control (<i>p</i>
DOI: 10.6084/m9.figshare.6291044.v1
title: Inhalation delivery of topotecan is superior to intravenous exposure for suppressing lung cancer in a preclinical model

description: Intravenous (IV) topotecan is approved for the treatment of various malignancies including lung cancer but its clinical use is greatly undermined by severe hematopoietic toxicity. We hypothesized that inhalation delivery of topotecan would increase local exposure and efficacy against lung cancer while reducing systemic exposure and toxicity. These hypotheses were tested in a preclinical setting using a novel inhalable formulation of topotecan against the standard IV dose. Respirable dry-powder of topotecan was manufactured through spray-drying technology and the pharmacokinetics of 0.14 and 0.79 mg/kg inhalation doses were compared with 0.7 mg/kg IV dose. The efficacy of four weekly treatments with 1 mg/kg inhaled vs. 2 mg/kg IV topotecan were compared to untreated control using an established orthotopic lung cancer model for a fast (H1975) and moderately growing (A549) human lung tumors in the nude rat. Inhalation delivery increased topotecan exposure of lung tissue by approximately 30-fold, lung and plasma half-life by 5- and 4-folds, respectively, and reduced the maximum plasma concentration by 2-fold than the comparable IV dose. Inhaled topotecan improved the survival of rats with the fast-growing lung tumors from 7 to 80% and reduced the tumor burden of the moderately-growing lung tumors over 5- and 10-folds, respectively, than the 2-times higher IV topotecan and untreated control (<i>p</i>
DOI: 10.6084/m9.figshare.5876655
title: Lipid-based nanocarrier efficiently delivers highly water soluble drug across the blood–brain barrier into brain

description: Delivering highly water soluble drugs across blood–brain barrier (BBB) is a crucial challenge for the formulation scientists. A successful therapeutic intervention by developing a suitable drug delivery system may revolutionize treatment across BBB. Efforts were given here to unravel the capability of a newly developed fatty acid combination (stearic acid:oleic acid:palmitic acid = 8.08:4.13:1) (ML) as fundamental component of nanocarrier to deliver highly water soluble zidovudine (AZT) as a model drug into brain across BBB. A comparison was made with an experimentally developed standard phospholipid-based nanocarrier containing AZT. Both the formulations had nanosize spherical unilamellar vesicular structure with highly negative zeta potential along with sustained drug release profiles. Gamma scintigraphic images showed both the radiolabeled formulations successfully crossed BBB, but longer retention in brain was observed for ML-based formulation (MGF) as compared to soya lecithin (SL)-based drug carrier (SYF). Plasma and brain pharmacokinetic data showed less clearance, prolonged residence time, more bioavailability and sustained release of AZT from MGF in rats compared to those data of the rats treated with SYF/AZT suspension. Thus, ML may be utilized to successfully develop drug nanocarrier to deliver drug into brain across BBB, in a sustained manner for a prolong period of time and may provide an effective therapeutic strategy for many diseases of brain. Further, many anti-HIV drugs cannot cross BBB sufficiently. Hence, the developed formulation may be a suitable option to carry those drugs into brain for better therapeutic management of HIV.
DOI: 10.6084/m9.figshare.5903767
title: New model of proliferative vitreoretinopathy in rabbit for drug delivery and pharmacodynamic studies

description: Blinding retinal diseases become more epidemic as the population ages. These diseases, such as diabetic retinopathy and macular edema, are of chronic nature and require protracted drug presence at the disease site. A sustained intravitreal porous silicon delivery system with dexamethasone (pSiO<sub>2</sub>-COO-DEX) was evaluated in a new rabbit model of proliferative vitreoretinopathy (PVR) in a real treatment design. In contrast to the pretreatment design model, pSiO<sub>2</sub>-COO-DEX was intravitreally injected into the eyes with active inflammation. Subretinal injection of vascular endothelial growth factor (VEGF) and Matrigel induced a late-onset vitreoretinal inflammation that gradually developed into PVR. This method mimics the human disease better than PVR induced by either intravitreal cell injection or trauma. The pSiO<sub>2</sub>-COO-DEX intervened eyes had minimal PVR, while balanced saline solution or free dexamethasone intervened eyes had significantly more PVR formation. In addition, adding VEGF to the Matrigel for subretinal injection induced greater inflammation and retinal neovascularization in comparison to only Matrigel injected under the medullary ray. Clinical and pathological examinations, including fundus fluorescein angiography and optical coherence tomography, confirmed these changes. In the current study, neither subretinal injection of Matrigel or subretinal injection of VEGF and Matrigel induced choroidal neovascularization. However, the current PVR model demonstrates a chronic course with moderate severity, which may be useful for drug screening studies.