17 results on '"Chu, Xiaoyang"'
Search Results
2. Correction: Biomimetic Antidote Nanoparticles: A Novel Strategy for Chronic Heavy Metal Poisoning.
- Author
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Wang H, Yao Q, Zhu W, Yang Y, Gao C, Chu X, and Han C
- Published
- 2023
- Full Text
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3. Biomimetic Antidote Nanoparticles: a Novel Strategy for Chronic Heavy Metal Poisoning.
- Author
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Wang H, Yao Q, Zhu W, Yang Y, Gao C, Han C, and Chu X
- Subjects
- Animals, Mice, Antidotes, Biomimetics, Heavy Metal Poisoning, Succimer therapeutic use, Nanoparticles, Lead Poisoning drug therapy
- Abstract
Chronic lead poisoning has become a major factor in global public health. Chelation therapy is usually used to manage lead poisoning. Dimercaptosuccinic acid (DMSA) is a widely used heavy metal chelation agent. However, DMSA has the characteristics of poor water solubility, low oral bioavailability, and short half-life, which limit its clinical application. Herein, a long-cycle slow-release nanodrug delivery system was constructed. We successfully coated the red blood cell membrane (RBCM) onto the surface of dimercaptosuccinic acid polylactic acid glycolic acid copolymer (PLGA) nanoparticles (RBCM-DMSA-NPs), which have a long cycle and detoxification capabilities. The NPs were characterized and observed by particle size meters and transmission electron microscopy. The results showed that the particle size of RBCM-DMSA-NPs was approximately 146.66 ± 2.41 nm, and the zeta potential was - 15.34 ± 1.60 mV. The homogeneous spherical shape and clear core-shell structure of the bionic nanoparticles were observed by transmission electron microscopy. In the animal tests, the area under the administration time curve of RBCM-DMSA-NPs was 156.52 ± 2.63 (mg/L·h), which was 5.21-fold and 2.36-fold that of free DMSA and DMSA-NPs, respectively. Furthermore, the median survival of the RBCM-DMSA-NP treatment group (47 days) was 3.61-fold, 1.32-fold, and 1.16-fold for the lead poisoning group, free DMSA, and DMSA-NP groups, respectively. The RBCM-DMSA-NP treatment significantly extended the cycle time of the drug in the body and improved the survival rate of mice with chronic lead poisoning. Histological analyses showed that RBCM-DMSA-NPs did not cause significant systemic toxicity. These results indicated that RBCM-DMSA-NPs could be a potential candidate for long-term chronic lead exposure treatment., (© 2022. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)
- Published
- 2022
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4. Betanin alleviates inflammation and ameliorates apoptosis on human oral squamous cancer cells SCC131 and SCC4 through the NF-κB/PI3K/Akt signaling pathway.
- Author
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Zou X, Yu K, Chu X, and Yang L
- Subjects
- Apoptosis, Cell Line, Tumor, Cell Proliferation, Humans, Inflammation drug therapy, NF-kappa B metabolism, Neoplasm Recurrence, Local, Phosphatidylinositol 3-Kinases metabolism, Proto-Oncogene Proteins c-akt metabolism, Reactive Oxygen Species metabolism, Betacyanins pharmacology, Mouth Neoplasms metabolism, Signal Transduction, Squamous Cell Carcinoma of Head and Neck metabolism
- Abstract
Oral squamous cell carcinoma (OSCC) is the prime kind of human malignancy with a great mortality ratio and a deprived prognosis due to its high level of relapse and metastasis. Recently reported is that betanin exerts a preventive role and cytotoxic activity on numerous cancer cells. Betanin comprises the betalain group, which is a highly bioavailable antioxidant. However, the precise molecular actions of betanin in the OSCC cells are yet to be elucidated. It may be the first report on the antiproliferative and apoptotic molecular mechanisms of betanin on OSCC. The current study intended to explore the betanin activity and its underlying mechanisms on SCC131 and SCC4 cells. The cytotoxicity assay, intracellular ROS, MMP, cell apoptosis, and inflammatory mediators of betanin activity on SCC131 and SCC4 cells were evaluated by MTT assay, DCFH-DA, Rh-123, AO/EB, DAPI, PI, analysis of western blot and RT-PCR. The upshots indicated that betanin restrains the SCC131 cells proliferation, MMP and inflammation, whereas induces apoptosis via the enhanced ROS level of SCC131 and SCC4 cells in a dose-dependent mode. Also, betanin-treated OSCC cells reduce inflammatory and apoptotic signaling pathways. The above-mentioned results exposed that betanin can inhibit cell viability, MMP, inflammation and enhanced apoptosis via the expression of NF-κB/PI3K/Akt pathways. Thus, our current findings provided an innovative vision into the protective effect against OSCC., (© 2022 Wiley Periodicals LLC.)
- Published
- 2022
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5. Bio-Inspired Hierarchical Micro-/Nanostructures for Anti-Icing Solely Fabricated by Metal-Assisted Chemical Etching.
- Author
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Zhang L, Chu X, Tian F, Xu Y, and Hu H
- Abstract
We report a cost-effective and scalable methodology for producing a hierarchical micro-/nanostructured silicon surface solely by metal-assisted chemical etching. It involves two major processing steps of fabricating micropillars and nanowires separately. The process of producing micro-scale structures by masked metal-assisted chemical etching was optimized. Silicon nanowires were created on the micropillar’s surface via maskless metal-assisted chemical etching. The hierarchical micro-/nanostructured surface exhibits superhydrophobic properties with a high contact angle of ~156° and a low sliding angle of <2.5° for deionized water. Furthermore, due to the existence of microscale and nanoscale air trapped at the liquid/solid interface, it exhibits a long ice delay time of 2876 s at −5 °C, more than 5 times longer than that of smooth surfaces. Compared to conventional dry etching methods, the metal-assisted chemical etching approach excludes vacuum environments and high-temperature processes and can be applied for applications requiring hierarchical micro-/nanostructured surfaces or structures.
- Published
- 2022
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6. Cepharanthine loaded nanoparticles coated with macrophage membranes for lung inflammation therapy.
- Author
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Lu C, Zheng J, Ding Y, Meng Y, Tan F, Gong W, Chu X, Kong X, and Gao C
- Subjects
- Animals, Animals, Outbred Strains, Benzylisoquinolines administration & dosage, Biomimetics, Delayed-Action Preparations, Disease Models, Animal, Drug Carriers chemistry, Drug Liberation, Human Umbilical Vein Endothelial Cells, Humans, Lipids chemistry, Male, Mice, Particle Size, RAW 264.7 Cells, Random Allocation, Benzylisoquinolines pharmacology, Macrophages metabolism, Nanoparticles chemistry, Pneumonia drug therapy
- Abstract
Acute lung injury (ALI) is a disease associated with suffering and high lethality, but to date without any effective pharmacological management in the clinic. In the pathological mechanisms of ALI, a strong inflammatory response plays an important role. Herein, based on macrophage 'homing' into inflammation sites and cell membrane coating nanotechnology, we developed a biomimetic anti-inflammation nanosystem (MM-CEP/NLCs) for the treatment of ALI. MM-CEP/NLCs were made with nanostructured lipid carriers (NLCs) coated with natural macrophage membranes (MMs) to achieve effective accumulation of cepharanthine (CEP) in lung inflammation to achieve the effect of treating ALI. With the advantage of suitable physicochemical properties of NLCs and unique biological functions of the macrophage membrane, MM-CEP/NLCs were stabilized and enabled sustained drug release, providing improved biocompatibility and long-term circulation. In vivo , the macrophage membranes enabled NLCs to be targeted and accumulated in the inflammation sites. Further, MM-CEP/NLCs significantly attenuated the severity of ALI, including lung water content, histopathology, bronchioalveolar lavage cellularity, protein concentration, and inflammation cytokines. Our results provide a bionic strategy via the biological properties of macrophages, which may have greater value and application prospects in the treatment of inflammation.
- Published
- 2021
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7. Cancer Cell Membrane-Coated Nanosuspensions for Enhanced Chemotherapeutic Treatment of Glioma.
- Author
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Fan Y, Hao W, Cui Y, Chen M, Chu X, Yang Y, Wang Y, and Gao C
- Subjects
- Animals, Antineoplastic Agents, Phytogenic adverse effects, Antineoplastic Agents, Phytogenic pharmacology, Blood-Brain Barrier drug effects, Blood-Brain Barrier pathology, Camptothecin adverse effects, Camptothecin analogs & derivatives, Camptothecin pharmacology, Camptothecin therapeutic use, Cell Line, Tumor, Endocytosis drug effects, Female, Humans, Male, Mice, Inbred ICR, Nanoparticles ultrastructure, Rats, Suspensions, Tissue Distribution drug effects, Treatment Outcome, Mice, Antineoplastic Agents, Phytogenic therapeutic use, Brain Neoplasms drug therapy, Brain Neoplasms pathology, Cell Membrane pathology, Glioma drug therapy, Glioma pathology, Nanoparticles chemistry
- Abstract
Effective intracerebral delivery is key for glioma treatment. However, the drug delivery system within the brain is largely limited by its own adverse physical and chemical properties, low targeting efficiency, the blood-brain barrier and the blood-brain tumor barrier. Herein, we developed a simple, safe and efficient biomimetic nanosuspension. The C6 cell membrane (CCM) was utilized to camouflaged the 10-hydroxycamptothecin nanosuspension (HCPT-NS) in order to obtain HCPT-NS/CCM. Through the use of immune escape and homotypic binding of the cancer cell membrane, HCPT-NS/CCM was able to penetrate the blood-brain barrier and target tumors. The HCPT-NS is only comprised of drugs, as well as a small amount of stabilizers that are characterized by a simple preparation method and high drug loading. Similarly, the HCPT-NS/CCM is able to achieve targeted treatment of glioma without any ligand modification, which leads it to be stable and efficient. Cellular uptake and in vivo imaging experiments demonstrated that HCPT-NS/CCM is able to effectively cross the blood-brain barrier and was concentrated at the glioma site due to the natural homing pathway. Our results reveal that the glioma cancer cell membrane is able to promote drug transport into the brain and enter the tumor via a homologous targeting mechanism.
- Published
- 2021
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8. Neuronal mitochondria-targeted therapy for Alzheimer's disease by systemic delivery of resveratrol using dual-modified novel biomimetic nanosystems.
- Author
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Han Y, Chu X, Cui L, Fu S, Gao C, Li Y, and Sun B
- Subjects
- Administration, Intravenous, Alzheimer Disease metabolism, Animals, Antioxidants pharmacokinetics, Antioxidants therapeutic use, Biological Transport drug effects, Biomimetic Materials pharmacokinetics, Biomimetic Materials therapeutic use, Blood-Brain Barrier drug effects, Blood-Brain Barrier metabolism, Brain metabolism, Cell Line, Drug Carriers chemistry, Drug Carriers pharmacokinetics, Drug Carriers therapeutic use, Erythrocyte Membrane chemistry, Male, Mice, Mice, Inbred ICR, Mitochondria metabolism, Nanoparticles metabolism, Nanoparticles therapeutic use, Neurons metabolism, Organophosphorus Compounds pharmacokinetics, Organophosphorus Compounds therapeutic use, Oxidative Stress drug effects, Rats, Sprague-Dawley, Reactive Oxygen Species metabolism, Resveratrol pharmacokinetics, Resveratrol therapeutic use, Tissue Distribution, Alzheimer Disease drug therapy, Antioxidants administration & dosage, Biomimetic Materials chemistry, Mitochondria drug effects, Nanoparticles chemistry, Neurons drug effects, Resveratrol administration & dosage
- Abstract
Reactive oxygen species (ROS)-induced neuronal mitochondrial dysfunction is a key pathologic factor in sporadic Alzheimer's disease (AD). Neuronal mitochondria have been proposed to be a promising therapeutic target for AD, especially for the failures of phase III clinical trials on conventional amyloid-β (Aβ) targeted therapy. However, the efficient intravenous delivery of therapeutic agents to neuronal mitochondria in the brain remains a major challenge due to the complicated physiological environment. Recently, biomaterials-based nanomedicine has been widely investigated for the treatment of AD. Herein, we devised a strategy for functional antioxidant delivery to neuronal mitochondria by loading antioxidants into red blood cell (RBC) membrane-coated nanostructured lipid carriers (NLC) bearing rabies virus glycoprotein (RVG29) and triphenylphosphine cation (TPP) molecules attached to the RBC membrane surface (RVG/TPP NPs@RBCm). With the advantage of suitable physicochemical properties of NLC and unique biological functions of the RBC membrane, RVG/TPP NPs@RBCm are stabilized and enabled sustained drug release, providing improved biocompatibility and long-term circulation. Under the synergistic effects of RVG29 and TPP, RVG/TPP NPs@RBCm can not only penetrate the blood-brain barrier (BBB) but also target neuron cells and further localize in the mitochondria. After encapsulating Resveratrol (RSV) as the model antioxidant, the data demonstrated that RVG/TPP-RSV NPs@RBCm can relieve AD symptoms by mitigating Aβ-related mitochondrial oxidative stress both in vitro and in vivo . The memory impairment in APP/PS1 mice is significantly improved following the systemic administration of RVG/TPP-RSV NPs@RBCm. In conclusion, intravenous neuronal mitochondria-targeted dual-modified novel biomimetic nanosystems are a promising therapeutic candidate for ROS-induced mitochondrial dysfunction in AD.
- Published
- 2020
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9. T807-modified human serum albumin biomimetic nanoparticles for targeted drug delivery across the blood-brain barrier.
- Author
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Gao C, Gong W, Yang M, Chu X, Wang Y, Li Z, Yang Y, and Gao C
- Subjects
- Animals, Biomimetics, Cell Survival, Chemistry, Pharmaceutical, Drug Carriers chemistry, Endothelial Cells, Mice, Phosphatidylethanolamines chemistry, Polyethylene Glycols chemistry, Rats, Rats, Sprague-Dawley, Blood-Brain Barrier metabolism, Carbolines pharmacokinetics, Erythrocyte Membrane metabolism, Nanoparticles chemistry, Serum Albumin, Human chemistry
- Abstract
Novel biocompatible Human Serum Albumin (HSA) nanoparticles composed of membrane of erythrocytes (ETm)-coated and DSPE-PEG
3400 -T807 segments have been designed for sustained drug delivery across the blood-brain barrier (BBB). The nanoparticles have developed by induced albumin self-assembly with glutathione as reducing agent. The chemical, physical and biocompatible properties of the T807/ETm-HSA nanoparticles have been characterised by hydrogen nuclear magnetic resonance, matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry, transmission electron microscopy, dynamic light scattering and confocal laser scanning microscopy techniques. The unique targeting properties of the nanoparticles after fabrication with the brain-targeted ligand T807 was demonstrated by their attaching to brain cells as well as their enhanced transport ability to cross the BBB. In a further demonstration of their ability to target brain cells, in vivo living imaging revealed that T807/ETm-HSA nanoparticles accumulated in the mice brain after intravenous injection. The surface modification of ETm/HSA nanoparticles with the brain-targeted T807 demonstrated in this work represents a highly novel and effective strategy to provide efficient brain targeting and shows promise for the future in using modified ETm-coated HSA nanoparticles to penetrate the brain.- Published
- 2020
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10. Neuron tau-targeting biomimetic nanoparticles for curcumin delivery to delay progression of Alzheimer's disease.
- Author
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Gao C, Chu X, Gong W, Zheng J, Xie X, Wang Y, Yang M, Li Z, Gao C, and Yang Y
- Subjects
- Animals, Apoptosis drug effects, Blood-Brain Barrier metabolism, Cell Line, Disease Models, Animal, Hippocampus drug effects, Hippocampus pathology, Humans, Maze Learning drug effects, Mice, Neurons metabolism, Protective Agents chemistry, Protective Agents pharmacokinetics, Protective Agents pharmacology, tau Proteins metabolism, Alzheimer Disease, Biomimetic Materials chemistry, Biomimetic Materials pharmacokinetics, Curcumin chemistry, Curcumin pharmacokinetics, Curcumin pharmacology, Drug Carriers chemistry, Drug Carriers pharmacokinetics, Nanoparticles chemistry
- Abstract
Background: Although many therapeutic strategies for Alzheimer's disease (AD) have been explored, these strategies are seldom used in the clinic. Therefore, AD therapeutic research is still urgently needed. One major challenge in the field of nanotherapeutics is to increase the selective delivery of drugs to a targeted location. Herein, we devised and tested a strategy for delivery of nanoparticles to neurons to inhibit tau aggregation by directly targeting p-tau., Results: Curcumin (CUR) is loaded onto red blood cell (RBC) membrane-coated PLGA particles bearing T807 molecules attached to the RBC membrane surface (T807/RPCNP). With the advantage of the suitable physicochemical properties of the PLGA nanoparticles and the unique biological functions of the RBC membrane, the RPCNP are stabilized and promote sustained CUR release, which provided improved biocompatibility and resulted in long-term presence in the circulation. Under the synergistic effects of T807, T807/RPCNP can not only effectively penetrate the blood-brain barrier (BBB), but they also possess high binding affinity to hyperphosphorylated tau in nerve cells where they inhibit multiple key pathways in tau-associated AD pathogenesis. When CUR was encapsulated, our data also demonstrated that CUR-loaded T807/RPCNP NPs can relieve AD symptoms by reducing p-tau levels and suppressing neuronal-like cells death both in vitro and in vivo. The memory impairment observed in an AD mouse model is significantly improved following systemic administration of CUR-loaded T807/RPCNP NPs., Conclusion: Intravenous neuronal tau-targeted T807-modified novel biomimetic nanosystems are a promising clinical candidate for the treatment of AD.
- Published
- 2020
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11. An HPLC-MS/MS method for quantitation of trelagliptin and application in a comparative pharmacokinetic study.
- Author
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Han Y, Chen L, Liu W, Xin X, Meng L, Chu X, Huang W, Jin M, and Gao Z
- Subjects
- Animals, Diabetes Mellitus drug therapy, Drug Monitoring methods, Female, Male, Rats, Sprague-Dawley, Reproducibility of Results, Uracil blood, Chromatography, High Pressure Liquid methods, Dipeptidyl-Peptidase IV Inhibitors blood, Hypoglycemic Agents blood, Piperidines blood, Tandem Mass Spectrometry methods, Uracil analogs & derivatives
- Abstract
Aim: A sensitive HPLC-MS/MS approach was established to quantify trelagliptin and explore the pharmacokinetic characteristics in rats for up to 7 days. Meanwhile, the pharmacokinetic differences of trelagliptin were investigated for the first time. Results/methodology: The ion pairs of m/z 358.2→341.2 for trelagliptin and m/z 340.3→116.1 for alogliptin (internal standard) were detected in positive mode. Trelagliptin displayed a good linearity in the range of 4-4000 ng/ml (r
2 = 0.9997) with a mean recovery rate of 86.9-94.1%. Discussion/conclusion: Compared with normal groups, the T1/2, apparent volume of distribution, area under the curve and bioavailability in model rats were significantly increased while the apparent plasma clearance decreased. The approach is proved to be straightforward and appropriate for quantitation of trelagliptin and application in pharmacokinetics studies.- Published
- 2019
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12. Improving glioblastoma therapeutic outcomes via doxorubicin-loaded nanomicelles modified with borneol.
- Author
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Meng L, Chu X, Xing H, Liu X, Xin X, Chen L, Jin M, Guan Y, Huang W, and Gao Z
- Subjects
- Animals, Antibiotics, Antineoplastic chemistry, Blood-Brain Barrier drug effects, Blood-Brain Barrier metabolism, Camphanes chemistry, Cell Line, Cell Survival drug effects, Doxorubicin chemistry, Drug Liberation, Humans, Male, Mice, Inbred ICR, Nanostructures chemistry, Rats, Wound Healing drug effects, Antibiotics, Antineoplastic administration & dosage, Brain Neoplasms drug therapy, Camphanes administration & dosage, Doxorubicin administration & dosage, Glioblastoma drug therapy, Micelles, Nanostructures administration & dosage
- Abstract
Glioblastoma is a grade IV malignant glioma with high recurrence and metastasis and faces a therapeutic obstacle that the blood-brain barrier (BBB) severely hinders the brain entry and efficacy of therapeutic drugs. Previous studies suggest that borneol (BO) has been used to enhance interested drugs to penetrate the BBB. In this study, a borneol-modified nanomicelle delivery system was established to facilitate the brain entry of doxorubicin for glioblastoma therapy. Herein, we firstly conjugated borneol molecules with DSPE-PEG
2000 -COOH to synthesize a novel carrier DSPE-PEG2000 -BO and also characterized its structure. Doxorubicin-loaded nanomicelles (DOX BO-PMs) were prepared using DSPE-PEG2000 -BO via electrostatic interaction and the physicochemical properties were investigated. The average particle size and zeta potential of DOX BO-PMs were respectively (14.95 ± 0.17)nm and (-1.27 ± 0.06)mV, and the drug encapsulation efficiency and loading capacity in DOX BO-PMs were (95.69 ± 0.49)% and (14.62 ± 0.39)%, respectively. The drug release of the DOX BO-PMs exhibited a both time- and pH-dependent pattern. The results demonstrated that DOX BO-PMs significantly enhanced the transport efficiency of DOX across the BBB and also exhibited a quick accumulation in the brain tissues. The in vitro anti-proliferation assay results suggested that DOX BO-PMs exerted a strong inhibitory effect on proliferation of glioblastoma cells. Importantly, in vivo antitumor results demonstrated that DOX BO-PMs significantly inhibited the tumor growth and metastasis of glioblastoma. In conclusion, DOX BO-PMs can improve the glioblastoma therapeutic outcomes and become a promising nanodrug candidate for the application of doxorubicin in the field of glioblastoma therapy., (Copyright © 2019 Elsevier B.V. All rights reserved.)- Published
- 2019
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13. Polymer Distribution and Mechanism Conversion in Multiple Media of Phase-Separated Controlled-Release Film-Coating.
- Author
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Chen L, Yang G, Chu X, Gao C, Wang Y, Gong W, Li Z, Yang Y, Yang M, and Gao C
- Abstract
Phase-separated films of water-insoluble ethyl cellulose (EC) and water-soluble hydroxypropyl cellulose (HPC) can be utilized to tailor drug release from coated pellets. In the present study, the effects of HPC levels and the pH, type, ionic strength and osmolarity of the media on the release profiles of soluble metoprolol succinates from the EC/HPC-coated pellets were investigated, and the differences in drug-release kinetics in multiple media were further elucidated through the HPC leaching and swelling kinetics of the pellets, morphology (SEM) and water uptake of the free films and the interaction between the coating polymers and the media compositions. Interestingly, the drug release rate from the pellets in different media was not in agreement with the drug solubility which have a positive correlation with the drug dissolution rate based on Noyes⁻Whitney equation law. In particular, the drug release rate in acetate buffer at pH 4.5 was faster than that in other media despite the solubility of drug was relatively lower, regardless of the HPC levels. It may be attributed to the mutual effect between the EC and acetate buffer, which improved the permeability of the film. In contrast, the release of drug in HCl solution was dependent on the HPC levels. Increasing the levels of HPC increased the effects of hydrogen ions on the polymer of HPC, which resulted in a lower viscosity and strength of the gel, forming the larger size of pores in polymer films, thus increasing the drug diffused from the coating film. Further findings in phosphate buffer showed a reduction in the drug release compared to that in other media, which was only sensitive to the osmolarity rather than the HPC level and pH of the buffer. Additionally, a mathematical theory was used to better explain and understand the experimentally measured different drug release patterns. In summary, the study revealed that the effects of the media overcompensated that of the drug solubility to some extent for controlled-release of the coating polymers, and the drug release mechanism in multiple media depend on EC and HPC rather than on HPC alone, which may have a potential to facilitate the optimization of ideally film-coated formulations.
- Published
- 2019
- Full Text
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14. Dual-Modified Novel Biomimetic Nanocarriers Improve Targeting and Therapeutic Efficacy in Glioma.
- Author
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Fu S, Liang M, Wang Y, Cui L, Gao C, Chu X, Liu Q, Feng Y, Gong W, Yang M, Li Z, Yang C, Xie X, Yang Y, and Gao C
- Subjects
- Animals, Blood-Brain Barrier pathology, Cell Line, Tumor, Female, Human Umbilical Vein Endothelial Cells, Humans, Male, Mice, Mice, Inbred ICR, Biomimetic Materials chemistry, Biomimetic Materials pharmacology, Blood-Brain Barrier metabolism, Brain Neoplasms drug therapy, Brain Neoplasms metabolism, Brain Neoplasms pathology, Drug Carriers chemistry, Drug Carriers pharmacology, Glioma drug therapy, Glioma metabolism, Glioma pathology, Nanoparticles chemistry, Nanoparticles therapeutic use, Oligopeptides chemistry, Oligopeptides pharmacology
- Abstract
Glioma is a fatal disease with limited treatment options and very short survival. Although chemotherapy is one of the most important strategies in glioma treatment, it remains extremely clinically challenging largely due to the blood-brain barrier (BBB) and the blood-brain tumor barrier (BBTB). Thus, the development of nanoparticles with both BBB and BBTB penetrability, as well as glioma-targeting feature, is extremely important for the therapy of glioma. New findings in nanomedicine are promoting the development of novel biomaterials. Herein, we designed a red blood cell membrane-coated solid lipid nanoparticle (RBCSLN)-based nanocarrier dual-modified with T7 and NGR peptide (T7/NGR-RBCSLNs) to accomplish these objectives. As a new kind of biomimetic nanovessels, RBCSLNs preserve the complex biological functions of natural cell membranes while possessing physicochemical properties that are needed for efficient drug delivery. T7 is a ligand of transferrin receptors with seven peptides that is able to circumvent the BBB and target to glioma. NGR is a peptide ligand of CD13 that is overexpressed during angiogenesis, representing an excellent glioma-homing property. After encapsulating vinca alkaloid vincristine as the model drug, T7/NGR-RBCSLNs exhibited the most favorable antiglioma effects in vitro and in vivo by combining the dual-targeting delivery effect. The results demonstrate that dual-modified biomimetic nanoparticles provide a potential method to improve drug delivery to the brain, hence increasing glioma therapy efficacy.
- Published
- 2019
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15. Enhanced blood-brain barrier penetration and glioma therapy mediated by T7 peptide-modified low-density lipoprotein particles.
- Author
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Liang M, Gao C, Wang Y, Gong W, Fu S, Cui L, Zhou Z, Chu X, Zhang Y, Liu Q, Zhao X, Zhao B, Yang M, Li Z, Yang C, Xie X, Yang Y, and Gao C
- Subjects
- Animals, Antineoplastic Agents, Phytogenic administration & dosage, Antineoplastic Agents, Phytogenic pharmacology, Brain Neoplasms pathology, Drug Carriers, Drug Delivery Systems, Excipients, Female, Glioma pathology, Humans, Lipoproteins, LDL chemistry, Mice, Mice, Inbred ICR, Nanoparticles, Receptors, Transferrin chemistry, Vincristine administration & dosage, Vincristine pharmacology, Zebrafish, Angiogenesis Inhibitors chemistry, Angiogenesis Inhibitors therapeutic use, Blood-Brain Barrier metabolism, Brain Neoplasms drug therapy, Collagen Type IV chemistry, Collagen Type IV therapeutic use, Glioma drug therapy, Peptide Fragments chemistry, Peptide Fragments therapeutic use
- Abstract
Therapeutic outcome for the treatment of glioma was often limited due to the non-targeted nature and low permeability of drugs across the blood-brain barrier (BBB). An ideal glioma-targeted delivery system need to traverse the BBB and then target glioma cells with adequate optimized physiochemical properties and biocompatibility. However, it is an enormous challenge to the researchers to engineer the above-mentioned features into a single nanocarrier particle. New frontiers in nanomedicine are advancing the research of new biomaterials. In this study, we demonstrate a strategy for glioma targeting by encapsulating vincristine sulfate (VCR) into a naturally available low-density lipoprotein particles (LDL)-based drug delivery system with the modification of T7 peptide ligand (T7-LDL). LDL, endogenous lipid transporters, can specifically bind to brain endothelial cells and glioma cells via interacting with the low-density lipoprotein receptors (LDLR). T7 is a seven-peptide ligand of transferrin receptors (TfR) capable of circumventing the BBB and then targeting glioma. By combining the dual-targeting delivery effect of T7 peptide and parent LDL, T7-LDL displayed higher glioma localization than that of parent LDL. After loading with VCR, T7-LDL showed the most favorable antiglioma effect in vitro and in vivo. These results demonstrated that T7-LDL is an important potential drug delivery system for glioma-targeted therapy.
- Published
- 2018
- Full Text
- View/download PDF
16. Dual-modified natural high density lipoprotein particles for systemic glioma-targeting drug delivery.
- Author
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Cui L, Wang Y, Liang M, Chu X, Fu S, Gao C, Liu Q, Gong W, Yang M, Li Z, Yu L, Yang C, Su Z, Xie X, Yang Y, and Gao C
- Subjects
- Animals, Antineoplastic Agents, Phytogenic administration & dosage, Antineoplastic Agents, Phytogenic pharmacokinetics, Antineoplastic Agents, Phytogenic therapeutic use, Blood-Brain Barrier metabolism, Camptothecin administration & dosage, Camptothecin analogs & derivatives, Camptothecin pharmacokinetics, Camptothecin therapeutic use, Cell Line, Tumor, Cell Survival drug effects, Drug Delivery Systems methods, Drug Liberation, Female, Human Umbilical Vein Endothelial Cells, Humans, Male, Mice, Inbred ICR, Brain Neoplasms drug therapy, Drug Carriers chemistry, Glioma drug therapy, Lipoproteins, HDL chemistry, Nanoparticles chemistry, Peptide Fragments chemistry
- Abstract
Therapeutic outcome for the treatment of glioma was often limited due to the two barriers involved: the blood-brain barrier (BBB) and blood-brain tumor barrier (BBTB). Therefore, the development of nanocarriers that possess both BBB and BBTB permeability and glioma-targeting ability is of great importance for the chemotherapy of glioma. New frontiers in nanomedicine are advancing the research of new biomaterials. Here we constructed a natural high-density lipoprotein particle (HDL)-based drug delivery system with the dual-modification of T7 and
d A7R peptide ligand (T7/d A7R-HDL) to achieve the above goals. HDL, the smallest lipoprotein, plays a biological role and is highly suitable as a platform for delivering imaging and therapeutic agents. T7 is a seven-peptide ligand of transferrin receptors (TfR) capable of circumventing the BBB and then targeting glioma.d A7R is a d-peptide ligand of vascular endothelial growth factor receptor 2 (VEGFR 2) overexpressed on angiogenesis, presenting excellent glioma-homing property. 10-Hydroxycamptothecin (HCPT), a hydrophobic anti-cancer drug, was used as the model drug in this study. By combining the dual-targeting delivery effect, the dual-modified HDL displayed higher glioma localization than that of single ligand-modified HDL or free HCPT. After loading with HCPT, T7/d A7R-HDL showed the most favorable anti-glioma effect in vivo. These results demonstrated that the dual-targeting natural nanocarriers strategy provides a potential method for improving brain drug delivery and anti-glioma treatment efficacy.- Published
- 2018
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17. Systematic Development of Self-Nanoemulsifying Liquisolid Tablets to Improve the Dissolution and Oral Bioavailability of an Oily Drug, Vitamin K1.
- Author
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Tong Y, Wang Y, Yang M, Yang J, Chen L, Chu X, Gao C, Jin Q, Gong W, and Gao C
- Abstract
The purpose of this study is to improve the dissolution and oral bioavailability of an oily drug, vitamin K1 (VK1) by combination of self-nanoemulsifying and liquisolid technologies. The optimal liquid self-nanoemulsifying drug delivery systems (SNEDDS) formulation including VK1 (oil), mixture of soybean lecithin and glycocholic acid (surfactant) and Transcutol HP (cosurfactant) was obtained according to ternary phase diagrams and a central composite design. Based on compatibility, adsorption capacity and dissolution profile, liquid SNEDDS was then solidified on Fujicalin
® to form solid SNEDDS by liquisolid technology and compressed directly with excipients into self-nanoemulsifying liquisolid (SNE-L) tablets. Uniform nano-emulsion suspension was formed rapidly when the SNE-L tablets disintegrated in dissolution media and higher drug dissolution was observed compared with the conventional tablets. The results of pharmacokinetic study in beagle dogs showed that the mean Cmax and the area under the curve of SNE-L tablets were remarkably higher than those of conventional tablets, which were consistent with the results of the in vitro dissolution. The relative bioavailability of SNE-L tablets and conventional tablets was approximately 200%. In conclusion, this combination method showed promise to improve the dissolution and oral bioavailability of oily drug vitamin K1.- Published
- 2018
- Full Text
- View/download PDF
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