JOURNAL OF COORDINATION CHEMISTRY
·
2025
·
IF 2.1
Mingzhe Li,Yuyang Zhou,Hua Zhou,Dingqiang Lu
Vitamin E is an important fat soluble antioxidant, its acetate is the main derivative product of vitamin E. Using metal organic framework material ZIF-8 as a catalyst, vitamin E acetate (VEA) was prepared by catalyzing the esterification reaction of D-α-tocopherol and acetic anhydride in a solvent-free system. Firstly, the preparation conditions of metal organic framework materials were studied: different imidazole ligands, different zinc ion ligands, molar concentration ratio of Zn2+ to 2-methylimidazole(2-mIM), and preparation time. The results showed that the catalytic performance of ZIF-8 was optimal when Zn(CH3COO)2·2H2O was used as the zinc source, 2-mIM was used as the imidazole ligand, the molar concentration ratio of Zn2+ / 2-mIM was 1:20, and the preparation time was 1 hour. The yield of vitamin E acetate was 86.85%. The synthesis process of VEA was optimized by single factor experiments such as substrate molar ratio, reaction time, dosage of nano enzyme, reaction temperature and so on. The results showed that the yield of vitamin E acetate reached 96.31% under the optimal conditions of n (D-α-tocopherol) =1mmol, [n (D-α-tocopherol) : n (Acetic anhydride)] =1:15, reaction time 24 h, ZIF-8 dosage 0.05 g, reaction temperature 50 °C.
研究领域:
化学
·
生物学
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产品关联
DOI
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2014
·
IF 7.261
Zhigui Su,Minglei Chen,Yanyu Xiao,Minjie Sun,Li Zong,Sajid Asghar,Mei Dong,Huipeng Li,Qineng Ping,Can Zhang
Drug delivery strategies utilizing tumor microenvironment are recognized as a critical doorway to overcome multidrug resistance (MDR). However, the variability of tumor microenvironment at different disease stages would definitely minimize stimuli generation and eventually the therapeutic effects of these stimuli sensitive systems. Herein, we report a unique reactive oxygen species (ROS) triggered nanosystem that can replenish the ROS upon disassembly to maintain its high level. This was accomplished by a new amphiphilic polymer (TBH) composed of D-α-tocopherol polyethylene glycol 1000 succinate (TPGS), hyaluronic acid (HA) and arylboronic ester. As a linker of TPGS to HA, arylboronic ester could efficiently degrade in response to ROS resulting in dismantling of nanosystem followed by rapid release of TPGS. Owing to ROS inducing activity of TPGS with mitochondrial respiratory complex II , ROS regeneration was observed for TBH nanosystem both in MCF-7/ADR cells and tumor tissues xenografted with MCF-7/ADR cells. Furthermore, doxorubicin-loaded TBH nanosystem (DOX-TBH) revealed higher drug cytotoxicity due to enhanced retention effect on account of ROS triggered DOX release and P-gp inhibitory mechanism of TPGS. Moreover, HA significantly improved tumor targeting capability of DOX-TBH, while ROS based triggering and regenerating mechanism lead to marked inhibition of the tumor growth in the xenograft MCF-7/ADR tumor-bearing nude mice .
研究领域:
肿瘤学
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药物递送
·
生物材料
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DOI
PubMed
高影响因子
Journal of Zhejiang University-SCIENCE B
·
2019
·
IF 1.879
Su-fang Gu,Li-ying Wang,Ying-jie Tian,Zhu-xian Zhou,Jian-bin Tang,Xiang-rui Liu,Hai-ping Jiang,You-qing Shen
Hesperetin, an abundant bioactive component of citrus fruits, is poorly water-soluble, resulting in low oral bioavailability. We developed new formulations to improve the water solubility, antioxidant activity, and oral absorption of hesperetin. Two nano-based formulations were developed, namely hesperetin-TPGS ( D -α-tocopheryl polyethylene glycol 1000 succinate) micelles and hesperetin-phosphatidylcholine (PC) complexes. These two formulations were prepared by a simple technique called solvent dispersion, using US Food and Drug Administration (FDA)-approved excipients for drugs. Differential scanning calorimetry (DSC) and dynamic light scattering (DLS) were used to characterize the formulations’ physical properties. Cytotoxicity analysis, cellular antioxidant activity assay, and a pharmacokinetic study were performed to evaluate the biological properties of these two formulations. The final weight ratios of both hesperetin to TPGS and hesperetin to PC were 1:12 based on their water solubility, which increased to 21.5-and 20.7-fold, respectively. The hesperetin-TPGS micelles had a small particle size of 26.19 nm, whereas the hesperetin-PC complexes exhibited a larger particle size of 219.15 nm. In addition, the cellular antioxidant activity assay indicated that both hesperetin-TPGS micelles and hesperetin-PC complexes increased the antioxidant activity of hesperetin to 4.2-and 3.9-fold, respectively. Importantly, the in vivo oral absorption study on rats indicated that the micelles and complexes significantly increased the peak plasma concentration ( C max ) from 2.64 μg/mL to 20.67 and 33.09 μg/mL and also increased the area under the concentration–time curve of hesperetin after oral administration to 16.2-and 18.0-fold, respectively. The micelles and complexes increased the solubility and remarkably improved the in vitro antioxidant activity and in vivo oral absorption of hesperetin, indicating these formulations’ potential applications in drugs and healthcare products.
研究领域:
药剂学
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营养学
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生物化学
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产品关联
DOI
PubMed
高影响因子
Pharmaceutics
·
2024
·Vol. 16
·期 2
·213
·
IF 4.9
Jiahui Ding,Handan Zhang,Tianli Dai,Xueqin Gao,Zhongyuan Yin,Qiong Wang,Mengqi Long,Songwei Tan
Poly (β-amino ester) (PBAE) is an exceptional non-viral vector that is widely used in gene delivery, owing to its exceptional biocompatibility, easy synthesis, and cost-effectiveness. However, it carries a high surface positive charge that may cause cytotoxicity. Therefore, hydrophilic d-α-tocopherol polyethylene glycol succinate (TPGS) was copolymerised with PBAE to increase the biocompatibility and to decrease the potential cytotoxicity of the cationic polymer-DNA plasmid polyplex nanoparticles (NPs) formed through electrostatic forces between the polymer and DNA. TPGS-b-PBAE (TBP) copolymers with varying feeding molar ratios were synthesised to obtain products of different molecular weights. Their gene transfection efficiency was subsequently evaluated in HEK 293T cells using green fluorescent protein plasmid (GFP) as the model because free GFP is unable to easily pass through the cell membrane and then express as a protein. The particle size, ζ-potential, and morphology of the TBP2-GFP polyplex NPs were characterised, and plasmid incorporation was confirmed through gel retardation assays. The TBP2-GFP polyplex NPs effectively transfected multiple cells with low cytotoxicity, including HEK 293T, HeLa, Me180, SiHa, SCC-7 and C666-1 cells. We constructed aMUC2(Mucin2)-targeting CRISPR/cas9 gene editing system in HEK 293T cells, with gene disruption supported by oligodeoxynucleotide (ODN) insertion in vitro. Additionally, we developed anLMP1(latent membrane protein 1)-targeting CRISPR/cas9 gene editing system in LMP1-overexpressing SCC7 cells, which was designed to cleave fragments expressing the LMP1 protein (related to Epstein–Barr virus infection) and thus to inhibit the growth of the cells in vivo. As evidenced by in vitro and in vivo experiments, this system has great potential for gene therapy applications.Keywords:poly (β-amino ester);gene transfection;D-α-tocopherol polyethylene glycol succinate;copolymer;CRISPR/cas9 gene editing;gene therapy
研究领域:
生物技术
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基因治疗
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药学
·
分子生物学
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DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2022
·
IF 5.062
Wan Liu,Meng Cheng,Fangying Yuan,Jiaying He,Yulin Feng,Yi Jin,Jianfang Feng,Shilin Yang,Liangxing Tu
Nanocrystal technology is a common strategy to enhance the oral bioavailability of poorly-soluble drugs, and how to enlarge the enhancing ability on oral absorption via nanocrystals has become a pharmaceutical research field. In this study, we selected andrographolide (ADR), a typical poorly-soluble drug, as the model drug, and employed sodium dodecyl sulfate and D-ɑ-Tocopherol polyethylene glycol 1000 succinate copolymer (SDS-TPGS) to construct novel SDS-TPGS modified andrographolide nanocrystals (S-TANs). We found that the particle sizes of SDS/TPGS physical mixture modified nanocrystals (STANs) were about 553.4 ± 4.1 nm , while that of SDS-TPGS modified nanocrystals (S-TANs) were 604.6 ± 5.7 nm. During the production process of nanocrystals, the crystallinity of ADR was slightly decreased. Nanocrystals enhanced the saturation solubility of ADR, and improved oral absorption, C max and AUC 0-∞ of S-TANs was about 2.10 and 1.24 fold increased, STAN about 2.63, 2.97 fold. In a Real-time distribution study, we found the distribution time of andrographolide, SDS and TPGS in SDS/TPGS physical mixture modified nanocrystals system varies widely, while the distribution times of these materials were similar in SDS-TPGS copolymer modified nanocrystals system. These results indicated that modified with functional stabilizer was an efficient strategy to enlarge the enhancing ability on oral absorption of nanocrystals, and synthesized copolymer containing different functional stabilizers showed higher ability on enhancing oral bioavailability than physical mixtures.
研究领域:
药学
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纳米技术
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药物递送系统
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产品关联
DOI
高影响因子
FOOD CHEMISTRY
·
2023
·
IF 8.8
Yimei Zheng,Chengang Zhao,Boyu Chen,Hui Teng,Chao Ai,Lei Chen
In the present study, D-α-Tocopherol polyethylene glycol 1000 succinate-based self-microemulsifying drug delivery systems (TPGS-SMEDDS) were introduced to enhance the solubility and stability of luteolin. The ternary phase diagrams were constructed to obtain the maximum area of microemulsion and suitable formulations of TPGS-SMEDDS. The particle size distribution and polydispersity index of selected TPGS-SMEDDS were analyzed to be less than 100 nm and 0.4, respectively. The thermodynamic stability results suggested that the TPGS-SMEDDS was stable during the heat-cool and freeze–thaw cycle. Moreover, the TPGS-SMEDDS exhibited excellent encapsulation capacity (51.21 ± 4.39 to 85.71 ± 2.40%) and loading efficiency (61.46 ± 5.27 to 102.86 ± 2.88 mg/g) to luteolin. In addition, the TPGS-SMEDDS showed an admirable vitro release ability with a ratio of more than 88.40 ± 1.14% for luteolin in 24 h. Therefore, TPGS-based SMEDDS might provide an effective role for the oral administration of luteolin and holds promise as a potential delivery for poorly soluble bioactive compounds.
研究领域:
药剂学
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药物递送系统
·
药物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2019
·
IF 3.973
Lifen Wang,Pengpeng Xue,Mengqi Tong,Rui Chen,Waigeng Yang,Deli ZhuGe,Jiandong Yuan,Qing Yao,Yingzheng Zhao,Helin Xu
Inflammatory bowel diseases (IBDs) are chronic relapsing disorders of the gastrointestinal tract characterized pathologically by intestinal inflammation and epithelial injury. Laquinimod (LAQ), a poorly water-soluble compound, was proved to be effective for colitis remission at low dose of 0.5 mg/kg in patients with Crohn’s disease. Due to its extremely low solubility in water, it was difficult to develop an injectable liquid dosage form. Herein, D-α-Tocopheryl polyethylene glycol-1000 succinate (TPGS) polymeric micelles were developed as a delivery vehicle of LAQ for the management of inflammatory bowel disease. Using the LAQ/TPGS ratio of 1:100, LAQ-loaded micelles were successfully prepared by thin-film dispersion method. The solubility of LAQ in water was significantly increased from 10.5 μg/mL in pure water to 500 μg/mL in TPGS micelles. LAQ-loaded micelles of TPGS exhibited the fine particle size of 34.6 nm and Zeta potential of -0.67 mV. Moreover, the good stability of LAQ-loaded micelles in physiology-mimicking medium was confirmed by detecting their particle size, zeta potential and leakage of the loading drug. Therapeutic effect of LAQ-loaded micelles on DSS-induced mice was proved by detecting DAI score, colon length and loss of body weight. Moreover, the morphology and colonic mucosal barrier of the injured colon of DSS-induced mice was largely recovered after treatment with LAQ-loaded micelles. Meanwhile, the inflammation of colitis colon was also obviously alleviated by LAQ-loaded micelles. Conclusively, polymeric micelles of TPGS may be a promising delivery vehicle of LAQ for the management of inflammatory bowel disease.
研究领域:
药学
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药理学
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药物递送系统
·
胃肠病学
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DOI
PubMed
高影响因子
Nature Communications
·
2022
·Vol. 13
·期 1
·1-17
·
IF 17.694
Wang Xiaojuan,Xu Xiaoling,Zhang Shaojun,Chen Na,Sun Yunfeng,Ma Kuifen,Hong Dongsheng,Li Lu,Du Yongzhong,Lu Xiaoyang,Jiang Saiping
Tigecycline is regarded as the last line of defense to combat multidrug-resistant Klebsiella pneumoniae . However, increasing utilization has led to rising drug resistance and treatment failure. Here, we design a D-alpha tocopheryl polyethylene glycol succinate-modified and S-thanatin peptide-functionalized nanorods based on calcium phosphate nanoparticles for tigecycline delivery and pneumonia therapy caused by tigecycline-resistant Klebsiella pneumoniae . After incubation with bacteria, the fabricated nanorods can enhance tigecycline accumulation in bacteria via the inhibitory effect on efflux pumps exerted by D-alpha tocopheryl polyethylene glycol succinate and the targeting capacity of S-thanatin to bacteria. The synergistic antibacterial capacity between S-thanatin and tigecycline further enhances the antibacterial activity of nanorods, thus overcoming the tigecycline resistance of Klebsiella pneumoniae . After intravenous injection, nanorods significantly reduces the counts of white blood cells and neutrophils, decreases bacterial colonies, and ameliorates neutrophil infiltration events, thereby largely increasing the survival rate of mice with pneumonia. These findings may provide a therapeutic strategy for infections caused by drug-resistant bacteria.
研究领域:
药学
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纳米技术
·
传染病学
·
生物医学工程
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产品关联
DOI
PubMed
高影响因子
ACS Applied Bio Materials
·
2020
·
IF 0
Zhicheng Le,Zhijia Liu,Lilong Sun,Lixin Liu,Yongming Chen
Dysregulated inflammation is considered as an essential pathological process in inflammation-associated diseases, which would be aggravated by high levels of reactive oxygen species (ROS) generation inducing oxidative stress. Currently, extensive attention has been paid to polyphenolic compounds owing to their broad spectrum biological activities, such as antioxidant and anti-inflammatory effects, while their therapeutic potential has been compromised by the poor stability, short plasma half-life, and low bioavailability. Given that polyphenols have a wide range of structural characteristics and various physicochemical properties, there remains a real challenge toward green, mass production of universal nanocarriers for effective entrapment of these active pharmaceutical ingredients. In this study, we adopted a flash nanocomplexation (FNC) platform to prepare nanocomplexes comprising polyphenols and d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) enabled by hydrogen bonding. We confirmed that the molecular structure of polyphenols has a great influence on their complexation with TPGS, and stable nanocomplexes were formed when the number of phenolic hydroxyl groups of polyphenols was above the value of 8. These hydrogen-bonded nanocomplexes produced by an FNC apparatus exhibited well-controlled quality with uniform size, good colloidal stability, and high batch-to-batch repeatability, thus improving the druggability as potent nanotherapeutics for antioxidant and anti-inflammatory applications. In vivo experiments indicated that the optimal nanocomplex (EGCG-NC) can be applied to ameliorate acute lung injury in a mice model after nasal administration. These results proved that polyphenols formulated with TPGS for nanocomplex formation through hydrogen-bonding complexation could augment their therapeutic potential for modulating hyperactive inflammation in the treatment of acute lung inflammation.
研究领域:
药理学
·
纳米技术
·
炎症
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
JOURNAL OF MICROENCAPSULATION
·
2021
·
IF 3.142
Zhumei Ge,Qilong Wang,Qin Zhu,Mukhtar Yusif,Jiangnan Yu,Ximing Xu
Herein, a nano-micelle drug delivery system was developed to orally improved zingerone’s bioavailability and its antitumor effect. Indeed, zingerone-loaded d-α-tocopheryl polyethylene glycol succinate micelles (ZTMs) were effectively prepared, characterised and assessed. The ZTMs had diameter, polydispersity index, and zeta potential of 50.62 ± 0.25 nm, 0.168 ± 0.006, and −28.07 ± 0.33 mV, respectively, coupled with a high entrapment efficiency (m/m, %) were 94.71 ± 2.02. The release rate of ZTMs in three media was significantly greater than that of free zingerone. Intriguingly, results obtained from pharmacokinetic studies showed that the oral bioavailability of the ZTMs was enhanced by 5.10 times in comparison with the free zingerone. Further, the half inhibitory concentration (IC50) of ZTMs and free zingerone was 7.56 μg/ml and 14.30 μg/ml, respectively, on HepG2 cells. Hence, ZTMs may be used as a potential approach to enrich the solubility, bioavailability, and concomitant anti-proliferative effect of zingerone in vitro.
研究领域:
药学
·
纳米技术
·
药物递送系统
·
癌症研究
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DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2024
·
IF 4.5
Hairong Chen,Guichun Wang,Xiaoliang Li,Jingjing Wang,Xinrui Wang,Yuxiao Wang,Zhenzhen Liu,Jiajia Liu,Yang Ding,Jian Guo,Shuangying Gui
Pueraria flavonoids (PF), the main component of “Getong Tongluo capsule”, were applied in the clinical treatment of cardiovascular diseases. However, the complex nature of multiple-components, along with poor stability and low oral bioavailability of PF, hinders its widespread clinical use. This study aimed to develop D-alpha-tocopheryl polyethylene glycol succinate (TPGS) surface-modified PF-loaded nanocrystals (PF–NCs)，and investigate their physico-chemical properties and oral absorption mechanism. The prepared PF-NCs showed as rod shape crystal with an average particle size and polydispersity index of 259.0 ± 7.80 nm and 0.195 ± 0.046. Compared with PF, the stability of PF-NCs was significantly improved. Furthermore, the transport of PF-NCs in Madin-Darby canine kidney (MDCK) monolayers was time-, concentration- and energy-dependent. The endocytosis of PF-NCs was mediated mainly through macropinocytosis, caveolin, clathrin and lipid rafts/caveolae. The involvement of multidrug resistance-associated protein 2 (MRP2) transporter and P-gp in the transmembrane transport of PF-NCs was also significant. Pharmacokinetic studies demonstrated that PF-NCs exhibited a substantial enhancement of PF's oral bioavailability. Overall, the prepared PF-NCs demonstrated enhanced stability and bioavailability, offering valuable insights for the development of multi-component nanocrystals and investigation into their mechanisms of oral absorption.
研究领域:
药剂学
·
纳米技术
·
药理学
·
生物药剂学
✓ 已验证
产品关联
DOI
高影响因子
MOLECULAR PHARMACEUTICS
·
2014
·
IF 4.787
Yuling Bao,Yuanyuan Guo,Xiangting Zhuang,Dan Li,Bolin Cheng,Songwei Tan,Zhiping Zhang
To overcome the multidrug resistance (MDR) of P-glycoprotein (P-gp) substrate anticancer drugs, such as paclitaxel (PTX), a novel dual-functional prodrug, D-α-tocopherol polyethylene glycol succinate (TPGS) based PTX prodrug (TPGS-S-S-PTX), was synthesized here to fulfill the synergistic effect of P-gp inhibiting and intracellular redox-sensitive release. The prodrug could self-assemble into stable micelles in physiological environment with a diameter of ∼140 nm, while it disassociated in reductive condition and released PTX and TPGS active derivatives rapidly. High cell cytotoxicity in PTX-resistant human ovarian cell line A2780/T was observed with enhanced PTX accumulation due to the P-gp inhibition by the TPGS moiety. The IC50 of TPGS-S-S-PTX was 55% and 91% more effective than that of Taxol (clinical formulation of PTX) and uncleavable TPGS-C-C-PTX prodrug, respectively. This was found to be related with the increased apoptosis/necrosis and cell arrest in G2/M phase. In vivo evaluation of the TPGS-S-S-PTX prodrug exhibited an extended half-life, increased AUC (area under the concentration–time curve), enhanced tumor distribution and significant tumor growth inhibition with reduced side effects as compared to Taxol and TPGS-C-C-PTX. This prodrug has great potential in improving efficiency in the treatment of MDR tumors.
研究领域:
药学
·
肿瘤学
·
药物递送系统
·
生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）