cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.20410681.v1
title: Improving cellular uptake and bioavailability of periplocymarin-linoleic acid prodrug by combining PEGylated liposome

description: Periplocymarin (PPM), a cardiac glycoside isolated from <i>Cortex periplocae</i>, has a strong anti-tumor effect against various cancer cells. However, cardiotoxicity and rapid metabolism hinder its clinical applications. In this study, small molecule prodrug was integrated into PEGylated liposome to improve the efficiency of periplocymarin <i>in vivo</i>. The periplocymarin-linoleic acid (PL) prodrug was constructed by conjugating the linoleic acid with PPM via esterification, which was further facilitated to form PEGylated liposome (PL-Lip) through film dispersion. Compared with PL self-assembling nano-prodrug (PL-SNP), PL-Lip showed better colloid stability, sustained drug release kinetics, and enhanced cellular uptake by tumor cells. Notably, PL-Lip performed better than PPM and PL-SNP in terms of tumor distribution and pharmacokinetics, which include bioavailability and half-life. Altogether, the prodrug PEGylated liposome represents a good strategy and method for long-circulating and tumor-targeting delivery of periplocymarin with enhanced clinical application prospect.
DOI: 10.6084/m9.figshare.20410681
title: Improving cellular uptake and bioavailability of periplocymarin-linoleic acid prodrug by combining PEGylated liposome

description: Periplocymarin (PPM), a cardiac glycoside isolated from <i>Cortex periplocae</i>, has a strong anti-tumor effect against various cancer cells. However, cardiotoxicity and rapid metabolism hinder its clinical applications. In this study, small molecule prodrug was integrated into PEGylated liposome to improve the efficiency of periplocymarin <i>in vivo</i>. The periplocymarin-linoleic acid (PL) prodrug was constructed by conjugating the linoleic acid with PPM via esterification, which was further facilitated to form PEGylated liposome (PL-Lip) through film dispersion. Compared with PL self-assembling nano-prodrug (PL-SNP), PL-Lip showed better colloid stability, sustained drug release kinetics, and enhanced cellular uptake by tumor cells. Notably, PL-Lip performed better than PPM and PL-SNP in terms of tumor distribution and pharmacokinetics, which include bioavailability and half-life. Altogether, the prodrug PEGylated liposome represents a good strategy and method for long-circulating and tumor-targeting delivery of periplocymarin with enhanced clinical application prospect.
DOI: 10.6084/m9.figshare.20516373
title: Development of microparticles for oral administration of <i>Periplaneta americana</i> extract to treat ulcerative colitis

description: Ulcerative colitis (UC) is a chronic disease, which can result the inflammation of the rectum, mucosa of the colon, and submucosa. The active component such as polypeptide in <i>Periplaneta americana</i>, which is one of the most common insects in the nature, can be extracted to treat UC. However, the active components in <i>Periplaneta americana</i> extract (PAE) can be degraded in the stomach due to its extreme acidic environment and enzyme. In this study, we developed a pH-dependent drug delivery method using polymer cellulose acetate (Eudragit S100) as a carrier to deliver high concentration PAE to inflamed colon. Both in vitro and in vivo results showed the PAE-Eudragit-S100 could treat UC through delivering active drug components to colon without degradation. Eudragit S100 polymer solution was mixed with PAE ethanol solution by sonicating. Then mixture was then mixed with lecithin and glycerol monooleate in a blender . The emulsion was stirred at room temperature with a magnetic stir bar at 420 rpm. Them the microparticles were freeze-dried in a freeze-dryer. Finally, When mice were treated with this drugs. the drugs were not decomposed in stomach and small intestine but damaged in the colon, which had a good curative effeet on colitis.
DOI: 10.6084/m9.figshare.20516373.v1
title: Development of microparticles for oral administration of <i>Periplaneta americana</i> extract to treat ulcerative colitis

description: Ulcerative colitis (UC) is a chronic disease, which can result the inflammation of the rectum, mucosa of the colon, and submucosa. The active component such as polypeptide in <i>Periplaneta americana</i>, which is one of the most common insects in the nature, can be extracted to treat UC. However, the active components in <i>Periplaneta americana</i> extract (PAE) can be degraded in the stomach due to its extreme acidic environment and enzyme. In this study, we developed a pH-dependent drug delivery method using polymer cellulose acetate (Eudragit S100) as a carrier to deliver high concentration PAE to inflamed colon. Both in vitro and in vivo results showed the PAE-Eudragit-S100 could treat UC through delivering active drug components to colon without degradation. Eudragit S100 polymer solution was mixed with PAE ethanol solution by sonicating. Then mixture was then mixed with lecithin and glycerol monooleate in a blender . The emulsion was stirred at room temperature with a magnetic stir bar at 420 rpm. Them the microparticles were freeze-dried in a freeze-dryer. Finally, When mice were treated with this drugs. the drugs were not decomposed in stomach and small intestine but damaged in the colon, which had a good curative effeet on colitis.
DOI: 10.6084/m9.figshare.17705136
title: Biodegradable hollow mesoporous organosilica nanotheranostics (HMONs) as a versatile platform for multimodal imaging and phototherapeutic-triggered endolysosomal disruption in ovarian cancer

description: A major impediment in the development of nanoplatform-based ovarian cancer therapy is endo/lysosome entrapment. To solve this dilemma, a hollow mesoporous organosilica-based nanoplatform (HMON@CuS/Gd<sub>2</sub>O<sub>3</sub>) with a mild-temperature photothermal therapeutic effect and multimodal imaging abilities was successfully synthesized. HMON@CuS/Gd<sub>2</sub>O<sub>3</sub> exhibited an appropriate size distribution, L-glutathione (GSH)-responsive degradable properties, and high singlet oxygen generation characteristics. In this study, the nanoplatform specifically entered SKOV-3 cells and was entrapped in endo/lysosomes. With a mild near infrared (NIR) power density (.5 W/cm<sup>2</sup>), the HMON@CuS/Gd<sub>2</sub>O<sub>3</sub> nanoplatform caused lysosome vacuolation, disrupted the lysosomal membrane integrity, and exerted antitumour effects in ovarian cancer. Additionally, our <i>in vivo</i> experiments indicated that HMON@CuS/Gd<sub>2</sub>O<sub>3</sub> has enhanced T1 MR imaging, fluorescence (FL) imaging (wrapping fluorescent agent), and infrared thermal (IRT) imaging capacities. Using FL/MRI/IRT imaging, HMON@CuS/Gd<sub>2</sub>O<sub>3</sub> selectively caused mild phototherapy in the cancer region, efficiently inhibiting the growth of ovarian cancer without systemic toxicity <i>in vivo</i>. Taken together, the results showed that these well-synthesized nanoplatforms are likely promising anticancer agents to treat ovarian cancer and show great potential for biomedical applications.
DOI: 10.6084/m9.figshare.17705136.v1
title: Biodegradable hollow mesoporous organosilica nanotheranostics (HMONs) as a versatile platform for multimodal imaging and phototherapeutic-triggered endolysosomal disruption in ovarian cancer

description: A major impediment in the development of nanoplatform-based ovarian cancer therapy is endo/lysosome entrapment. To solve this dilemma, a hollow mesoporous organosilica-based nanoplatform (HMON@CuS/Gd<sub>2</sub>O<sub>3</sub>) with a mild-temperature photothermal therapeutic effect and multimodal imaging abilities was successfully synthesized. HMON@CuS/Gd<sub>2</sub>O<sub>3</sub> exhibited an appropriate size distribution, L-glutathione (GSH)-responsive degradable properties, and high singlet oxygen generation characteristics. In this study, the nanoplatform specifically entered SKOV-3 cells and was entrapped in endo/lysosomes. With a mild near infrared (NIR) power density (.5 W/cm<sup>2</sup>), the HMON@CuS/Gd<sub>2</sub>O<sub>3</sub> nanoplatform caused lysosome vacuolation, disrupted the lysosomal membrane integrity, and exerted antitumour effects in ovarian cancer. Additionally, our <i>in vivo</i> experiments indicated that HMON@CuS/Gd<sub>2</sub>O<sub>3</sub> has enhanced T1 MR imaging, fluorescence (FL) imaging (wrapping fluorescent agent), and infrared thermal (IRT) imaging capacities. Using FL/MRI/IRT imaging, HMON@CuS/Gd<sub>2</sub>O<sub>3</sub> selectively caused mild phototherapy in the cancer region, efficiently inhibiting the growth of ovarian cancer without systemic toxicity <i>in vivo</i>. Taken together, the results showed that these well-synthesized nanoplatforms are likely promising anticancer agents to treat ovarian cancer and show great potential for biomedical applications.
DOI: 10.6084/m9.figshare.19650828
title: Preparation of baicalin-loaded ligand-modified nanoparticles for nose-to-brain delivery for neuroprotection in cerebral ischemia

description: Neuroprotection in cerebral ischemia (CI) has received increasing attention. However, efficient delivery of therapeutic agents to the brain remains a major challenge due to the complex environment of the brain. Nose-to-brain-based delivery is a promising approach. Here, we optimized a nanocarrier formulation of neuroprotective agents that can be used for nose-to-brain delivery by obtaining RVG29 peptide-modified polyethylene glycol–polylactic acid-co-glycolic acid nanoparticles (PEG–PLGA RNPs) that have physicochemical properties that lead to stable and sustained drug release and thereby improve the bioavailability of neuroprotective agents. The brain-targeting ability of PEG–PLGA RNPs administered through nasal inhalation was verified in a rat model of CI. It was found that delivery to the whole brain can be achieved with little delivery to the peripheral circulation. Baicalin (BA) was selected as the neuroprotective agent for delivery. After intranasal administration of BA–PEG–PLGA RNPs, the neurological dysfunction of rats with ischemic brain injury was significantly alleviated, the cerebral infarction area was reduced, and nerve trauma and swelling were relieved. Furthermore, it was demonstrated that the neuroprotective effects of BA in a rat model of CI may be mediated by inhibition of inflammation and alleviation of oxidative stress. The immunohistochemical results obtained after treatment with nanoparticles loaded with BA showed that Nrf2/HO-1 was activated in the area in which ischemic brain damage had occurred and that its expression was significantly higher in the group treated with BA–PEG–PLGA RNPs than in the other groups. The ELISA results showed that the levels of IL-1β, IL-6, and TNF-α were abnormally increased in the serum of rats with cerebral ischemia. After treatment with BA-loaded nanoparticles, IL-1β, IL-6, and TNF-α levels decreased significantly. Oxidative stress was alleviated; the levels of glutathione and superoxide dismutase increased; and the levels of reactive oxygen species and malondialdehyde decreased, in animals to which BA–PEG–PLGA RNPs were delivered by intranasal inhalation. In conclusion, BA–PEG–PLGA RNPs can effectively deliver BA to rats and thereby exert neuroprotective effects against CI.
DOI: 10.6084/m9.figshare.19650828.v1
title: Preparation of baicalin-loaded ligand-modified nanoparticles for nose-to-brain delivery for neuroprotection in cerebral ischemia

description: Neuroprotection in cerebral ischemia (CI) has received increasing attention. However, efficient delivery of therapeutic agents to the brain remains a major challenge due to the complex environment of the brain. Nose-to-brain-based delivery is a promising approach. Here, we optimized a nanocarrier formulation of neuroprotective agents that can be used for nose-to-brain delivery by obtaining RVG29 peptide-modified polyethylene glycol–polylactic acid-co-glycolic acid nanoparticles (PEG–PLGA RNPs) that have physicochemical properties that lead to stable and sustained drug release and thereby improve the bioavailability of neuroprotective agents. The brain-targeting ability of PEG–PLGA RNPs administered through nasal inhalation was verified in a rat model of CI. It was found that delivery to the whole brain can be achieved with little delivery to the peripheral circulation. Baicalin (BA) was selected as the neuroprotective agent for delivery. After intranasal administration of BA–PEG–PLGA RNPs, the neurological dysfunction of rats with ischemic brain injury was significantly alleviated, the cerebral infarction area was reduced, and nerve trauma and swelling were relieved. Furthermore, it was demonstrated that the neuroprotective effects of BA in a rat model of CI may be mediated by inhibition of inflammation and alleviation of oxidative stress. The immunohistochemical results obtained after treatment with nanoparticles loaded with BA showed that Nrf2/HO-1 was activated in the area in which ischemic brain damage had occurred and that its expression was significantly higher in the group treated with BA–PEG–PLGA RNPs than in the other groups. The ELISA results showed that the levels of IL-1β, IL-6, and TNF-α were abnormally increased in the serum of rats with cerebral ischemia. After treatment with BA-loaded nanoparticles, IL-1β, IL-6, and TNF-α levels decreased significantly. Oxidative stress was alleviated; the levels of glutathione and superoxide dismutase increased; and the levels of reactive oxygen species and malondialdehyde decreased, in animals to which BA–PEG–PLGA RNPs were delivered by intranasal inhalation. In conclusion, BA–PEG–PLGA RNPs can effectively deliver BA to rats and thereby exert neuroprotective effects against CI.
DOI: 10.1285/i20705948v16n3p711
title: A Permutation Test for Comparing Multiple Measures of Center in Three-Dimensional Rotation Data

description: Data in the form of three-dimensional rotations arise in various fields, yet statistical techniques for modeling such data receive far less focus in the area of directional statistics than circular and spherical data. In this paper, the focus is on comparison of mean or central matrices for multiple groups of three-dimensional rotations. A permutation test is developed by using the fundamental ideas behind a traditional Analysis of Variance and a simulation study is used to investigate the power of the permutation test under various conditions. The test is then used on a biomechanics data set to compare movement around the calcaneocuboid joint for a human, chimpanzee, and baboon.
DOI: 10.6084/m9.figshare.17891029
title: Milk exosomes-mediated miR-31-5p delivery accelerates diabetic wound healing through promoting angiogenesis

description: The refractory diabetic wound has remained a worldwide challenge as one of the major health problems. The impaired angiogenesis phase during diabetic wound healing partly contributes to the pathological process. MicroRNA (miRNA) is an essential regulator of gene expression in crucial biological processes and is a promising nucleic acid drug in therapeutic fields of the diabetic wound. However, miRNA therapies have limitations due to lacking an effective delivery system. In the present study, we found a significant reduction of miR-31-5p expression in the full-thickness wounds of diabetic mice compared to normal mice. Further, miR-31-5p has been proven to promote the proliferation, migration, and angiogenesis of endothelial cells. Thus, we conceived the idea of exogenously supplementing miR-31-5p mimics to treat the diabetic wound. We used milk-derived exosomes as a novel system for miR-31-5p delivery and successfully encapsulated miR-31-5p mimics into milk exosomes through electroporation. Then, we proved that the miR-31-5p loaded in exosomes achieved higher cell uptake and was able to resist degradation. Moreover, our miRNA-exosomal formulation demonstrated dramatically improved endothelial cell functions <i>in vitro</i>, together with the promotion of angiogenesis and enhanced diabetic wound healing <i>in vivo</i>. Collectively, our data showed the feasibility of milk exosomes as a scalable, biocompatible, and cost-effective delivery system to enhance the bioavailability and efficacy of miRNAs.
DOI: 10.6084/m9.figshare.17891029.v1
title: Milk exosomes-mediated miR-31-5p delivery accelerates diabetic wound healing through promoting angiogenesis

description: The refractory diabetic wound has remained a worldwide challenge as one of the major health problems. The impaired angiogenesis phase during diabetic wound healing partly contributes to the pathological process. MicroRNA (miRNA) is an essential regulator of gene expression in crucial biological processes and is a promising nucleic acid drug in therapeutic fields of the diabetic wound. However, miRNA therapies have limitations due to lacking an effective delivery system. In the present study, we found a significant reduction of miR-31-5p expression in the full-thickness wounds of diabetic mice compared to normal mice. Further, miR-31-5p has been proven to promote the proliferation, migration, and angiogenesis of endothelial cells. Thus, we conceived the idea of exogenously supplementing miR-31-5p mimics to treat the diabetic wound. We used milk-derived exosomes as a novel system for miR-31-5p delivery and successfully encapsulated miR-31-5p mimics into milk exosomes through electroporation. Then, we proved that the miR-31-5p loaded in exosomes achieved higher cell uptake and was able to resist degradation. Moreover, our miRNA-exosomal formulation demonstrated dramatically improved endothelial cell functions <i>in vitro</i>, together with the promotion of angiogenesis and enhanced diabetic wound healing <i>in vivo</i>. Collectively, our data showed the feasibility of milk exosomes as a scalable, biocompatible, and cost-effective delivery system to enhance the bioavailability and efficacy of miRNAs.
DOI: 10.6084/m9.figshare.19513671
title: Fenticonazole nitrate loaded trans-novasomes for effective management of tinea corporis: design characterization, <i>in silico</i> study, and exploratory clinical appraisal

description: The current investigation aimed for loading fenticonazole nitrate (FTN), an antifungal agent with low aqueous solubility, into trans-novasomes (TNs) for management of tinea corporis topically. TNs contain Brij<sup>®</sup> as an edge activator besides the components of novasomes (cholesterol, Span 60, and oleic acid) owing to augment the topical delivery of FTN. TNs were fabricated applying ethanol injection method based on D-optimal experiment. TNs were evaluated with regard to entrapment efficiency percent (EE%), particle size (PS), polydispersity index (PDI), and zeta potential (ZP). Further explorations were conducted on the optimum formulation (F7). F7 showed spherical appearance with EE%, PS, PDI, and ZP of 100.00 ± 1.10%, 358.60 ± 10.76 nm, 0.51 ± 0.004, and −30.00 ± 0.80 mV, respectively. The <i>in silico</i> study revealed the ability of the FTN–cholesterol complex to maintain favorable interactions throughout the molecular dynamics simulation (MDS) study. Moreover, <i>Trichophyton mentagrophytes</i> growth was inhibited effectively by F7 than by FTN suspension applying 2,3-bis(2-methyloxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) reduction assay. Furthermore, a clinical appraisal on patients with tinea corporis fungal lesions confirmed the superiority of F7 compared to Miconaz<sup>®</sup> cream in the magnitude of clinical cure of tinea corporis. Thereby, TNs could be considered as promising vesicles for enhancing the antifungal potential of FTN for the topical management of tinea corporis.
DOI: 10.6084/m9.figshare.19513671.v1
title: Fenticonazole nitrate loaded trans-novasomes for effective management of tinea corporis: design characterization, <i>in silico</i> study, and exploratory clinical appraisal

description: The current investigation aimed for loading fenticonazole nitrate (FTN), an antifungal agent with low aqueous solubility, into trans-novasomes (TNs) for management of tinea corporis topically. TNs contain Brij<sup>®</sup> as an edge activator besides the components of novasomes (cholesterol, Span 60, and oleic acid) owing to augment the topical delivery of FTN. TNs were fabricated applying ethanol injection method based on D-optimal experiment. TNs were evaluated with regard to entrapment efficiency percent (EE%), particle size (PS), polydispersity index (PDI), and zeta potential (ZP). Further explorations were conducted on the optimum formulation (F7). F7 showed spherical appearance with EE%, PS, PDI, and ZP of 100.00 ± 1.10%, 358.60 ± 10.76 nm, 0.51 ± 0.004, and −30.00 ± 0.80 mV, respectively. The <i>in silico</i> study revealed the ability of the FTN–cholesterol complex to maintain favorable interactions throughout the molecular dynamics simulation (MDS) study. Moreover, <i>Trichophyton mentagrophytes</i> growth was inhibited effectively by F7 than by FTN suspension applying 2,3-bis(2-methyloxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) reduction assay. Furthermore, a clinical appraisal on patients with tinea corporis fungal lesions confirmed the superiority of F7 compared to Miconaz<sup>®</sup> cream in the magnitude of clinical cure of tinea corporis. Thereby, TNs could be considered as promising vesicles for enhancing the antifungal potential of FTN for the topical management of tinea corporis.
DOI: 10.6084/m9.figshare.19355056
title: Bone-targeted nanoplatform enables efficient modulation of bone tumor microenvironment for prostate cancer bone metastasis treatment

description: As there is currently no effective therapy for patients with prostate cancer (PCa) bone metastasis, it was stringent to explore the relevant treatment strategies. Actually, the interaction between cancer cells and bone microenvironment plays important role in prostate cancer bone metastasis, especially the Sonic hedgehog protein (SHH) signaling in the bone microenvironment. The SHH promotes osteoblast maturation and osteoblast then secretes RANKL to induce osteoclastogenesis. Herein, this study develops bone-targeting calcium phosphate lipid hybrid nanoparticles (NPs) loaded with docetaxel (DTXL) and SHH siRNA for PCa bone metastasis treatment. For bone targeting purposes, the nanoplatform was modified with alendronate (ALN). (DTXL + siRNA)@NPs-ALN NPs effectively change the bone microenvironment by inhibiting the SHH paracrine and autocrine signaling, enhancing the anti-tumor effects of DTXL. Besides showing good <i>in vitro</i> cellular uptake, the NPs-ALN also inhibited tumor growth both <i>in vitro</i> and <i>in vivo</i> by inducing apoptosis, cell cycle arrest, and autophagy. This DDS comprised of (DTXL + siRNA)-loaded NPs provides an excellent strategy to treat PCa bone metastasis.
DOI: 10.6084/m9.figshare.19355056.v1
title: Bone-targeted nanoplatform enables efficient modulation of bone tumor microenvironment for prostate cancer bone metastasis treatment

description: As there is currently no effective therapy for patients with prostate cancer (PCa) bone metastasis, it was stringent to explore the relevant treatment strategies. Actually, the interaction between cancer cells and bone microenvironment plays important role in prostate cancer bone metastasis, especially the Sonic hedgehog protein (SHH) signaling in the bone microenvironment. The SHH promotes osteoblast maturation and osteoblast then secretes RANKL to induce osteoclastogenesis. Herein, this study develops bone-targeting calcium phosphate lipid hybrid nanoparticles (NPs) loaded with docetaxel (DTXL) and SHH siRNA for PCa bone metastasis treatment. For bone targeting purposes, the nanoplatform was modified with alendronate (ALN). (DTXL + siRNA)@NPs-ALN NPs effectively change the bone microenvironment by inhibiting the SHH paracrine and autocrine signaling, enhancing the anti-tumor effects of DTXL. Besides showing good <i>in vitro</i> cellular uptake, the NPs-ALN also inhibited tumor growth both <i>in vitro</i> and <i>in vivo</i> by inducing apoptosis, cell cycle arrest, and autophagy. This DDS comprised of (DTXL + siRNA)-loaded NPs provides an excellent strategy to treat PCa bone metastasis.