INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2017
·
IF 3.649
Xiumei Zhu,Altansukh Tsend-Ayush,Zhongyue Yuan,Jing Wen,Jiaxin Cai,Shifu Luo,Jianxu Yao,Junxing Bian,Linfang Yin,Jianping Zhou,Jing Yao
In this study, glycyrrhetinic acid (GA)-modified D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) polymeric micelles (TGA PMs) were developed for the delivery of etoposide (ETO) to hepatoma cells. GA was incorporated as a ligand because of its high affinity to the hepatocytes, while TPGS functioned as a P-gp inhibitor to reverse multidrug resistance. ETO-loaded TGA PMs (ETO-TGA PMs) displayed a mean particle size of 133.6 ± 1.2 nm with a low poly-dispersity index (0.224 ± 0.013) and negative zeta potential (−16.30 mV). The drug loading and entrapment efficiency of ETO-TGA PMs were 10.4% and 79.8%, respectively. ETO-TGA PMs also exhibited faster drug release behavior at pH 5.8 and relatively stable drug release at pH 7.4. Confocal laser scanning microscope (CLSM) observations and in vivo imaging studies revealed that TGA PMs displayed higher cellular uptake and selective accumulation at the tumor site, indicating good tumor targetability. Furthermore, ETO-TGA PMs displayed significant cytotoxicity towards HepG2 cells and higher anti-tumor efficacy (75.96%), compared to the control group. This could be due to TGA-mediated targeted drug delivery to the hepatocytes as well as P-gp inhibition. These findings suggest that TGA PMs have the potential to be used as a targeted drug delivery system for hepatic cancer therapy.
研究领域:
药剂学
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肿瘤学
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生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
Cell Reports Physical Science
·
2020
·
IF 0
Pengfei Zhang,Zhangliu Tian,Chin-Te Hung,Yong Liu,Bingquan Jia,Kun Lan,Biao Kong,Fuqiang Huang,Liqiang Mai,Dongyuan Zhao
The understanding and control of the structural complexity of mesoporous semiconductors with single-crystal-like nature are both attractive and challenging. Here, we report a crystallization-driven epitaxial assembly from monomicelles to construct branched mesoporous TiO 2 mesocrystals (m-TiO 2 MCs) with coherent atomic domains. The star-shaped multipods are obtained by two-step evaporation with nanocrystal mediation, primarily consisting of arms along < 001 >, < 101 >, and < 111 > crystal directions. For each arm, ordered open mesochannels arrange in parallel along the growth direction. The m-TiO 2 MC multipods have a surface area of ∼116 m 2 /g and single-crystal-like frameworks and are good hydrogen evolution photocatalysts. Under full-spectrum irradiation, the branched m-TiO 2 MCs exhibit a hydrogen evolution rate of 8 mmol h −1 g −1 , which is more than four times higher than that of commercial TiO 2 P25. This crystallization-driven self-assembly approach may provide valuable insight into designing programmable mesoporous mesocrystals by controlling the oriented assembly of monomicelle building blocks.
研究领域:
材料科学
·
化学
✓ 已验证
DOI
ACS Applied Materials & Interfaces
·
2018
·
IF 8.097
Yazhou Chen,Li Zhang,Yingjie Liu,Shiming Tan,Ruidan Qu,Zirong Wu,Yue Zhou,Jing Huang
Poly-γ-l-glutamic acid (PGA) is an outstanding drug carrier candidate owning to its excellent biodegradability and biocompatibility. The PGA carrier may shield toxic drugs from the body and enable the delivery of poorly soluble or unstable drugs and thereby minimize the side effects and improve drug efficacy. However, the limitation of PGA as a drug carrier is low drug loading efficiency (DLE), which is usually below 30%. In this study, we reported a chemical modification method using l-phenylalanine ethyl ester (PAE). PGA–PAE construct was amphiphilic, which could form micelles in aqueous solution. Cisplatin (CDDP), a commonly used chemotherapy drug whose side effect is well-known, was used as a model molecule to test the drug-loading efficiency of PGA–PAE. In this paper, two sizes of CDDP-loaded PGA–PAE micelles (M(Pt)-1 and M(Pt)-2) were prepared, the average diameter of M(Pt)-1 was 106 ± 6 nm and M(Pt)-2 was 210 ± 9 nm. The DLE of M(Pt)-1 and M(Pt)-2 was 52.8 ± 2.2 and 55.8 ± 1.2%, respectively. Both exhibited excellent biocompatibility, stability, and drug-retaining capability in physiological condition. The in vitro accumulative drug-releasing profile, IC50 for different tumor cell lines HeLa, A549, and HCCC9810, and in vivo pharmacokinetics were similar between these two micelles; however, M(Pt)-1 showed higher tumor tissue retention and longer efficient cancer cell internalization time (up to 20 d). Our results suggested PGA–PAE micelle carriers reduced the toxicity of CDDP and its size at around 100 nm was the better for CDDP high-efficacy.
研究领域:
药理学
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肿瘤学
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纳米技术
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF DRUG TARGETING
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2017
·
IF 3.068
Hongzhi Qiao,Zhenzhu Zhu,Dong Fang,Yuan Sun,Chen Kang,Liuqing Di,Lei Zhang,Yahan Gao
Multidrug resistance (MDR) severely hinders the efficient chemotherapeutic treatments of cancer. d-α-Tocopherol polyethylene 1000 succinate (TPGS) based drug delivery system holds the potential of re-sensitizing resistant cancer cells. In this study, a TPGS prodrug containing both TPGS and mitoxantrone (MTO) via a disulphide bond was synthesised and assembled into micelle (TSMm) with a monodispersed diameter of 46.50 ± 1.12 nm. The disulphide bonds within the micelles could be cleaved in response to a high concentration of intracellular glutathione (GSH) after entering the tumour cells, leading a rapid release of MTO. In vitro cytotoxicity study showed TSMm significantly inhibited the growth of resistant breast tumour cells MDA-MB-231/MDR comparing to either free MTO or disulphide-free prodrug micelle (TCMm). In addition, TSMm could sustain favourable intracellular retention and cause the depletion of ATP activity, leading to the preferential transportation of MTO into the nucleus and the reversal of MDR. In vivo imaging also verified that TSMm was specifically targeted to the tumour regions at 24 h post injection. Finally, TSMm has significantly stronger antitumor activity in xenograft nude mice with negligible side effects. Hence, TSMm can serve as promising prodrug candidates to strengthen the reversal of MDR in tumours with less side effects.
研究领域:
药理学
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肿瘤学
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药物递送系统
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癌症治疗
✓ 已验证
DOI
PubMed
高影响因子
Science China-Materials
·
2020
·Vol. 64
·期 1
·241-251
·
IF 6.098
Wu Pengkai,Yin Shuai,Liu Tianqing,Ding Dan,Wang Kaikai
Incorporating functional ligands and biodegradable bonds into biocompatible low-molecular-weight (LMW) polymers, such as 1.8 kDa poly(ethylenimine) (PEI 1.8k), is a common strategy to improve the properties of LMW polymers including biosafety and delivery efficacy. This study demonstrates the hypothesis that introducing different functional ligands and linked reductive disulfides in PEI 1.8k will achieve superior siRNA transfection efficiency. By incorporating PEI-X (X represents cholesterol (Ch), heptafluorobutyric anhydride (HFBA, F) and 4-carboxyphenylboronic acid (PBA)) functional ligands into PEI 1.8k and subsequently crosslinking with each other via disulfide bond links, reductive-responsive PEI-X-SS-X-PEI copolymers were constructed to enhance the cellular transfection via the synergistic effect of the high affinity of Ch, F and PBA to cell membranes and the disulfide reduction triggered intracellular disassembly of micelles and subsequent siRNA release. Extraordinarily, ternary Ch-SS-F-SS-PBA micelles exhibited the strongest siRNA transfection efficiencies in in vitro cell experiments and in vivo animal experiments due to the coordination of enhanced serum stability, promoted cell uptake and endosomal escape, and cell targeting ability. This strategy of constructed multifunctional polymer here we called “building-block crosslinking” showed a simple and smart way to synthesize new materials. Also this strategy of constructing ligands-directed reduction-sensitive micelles improves the transfection efficiency of LMW PEI and provides a valuable insight to develop novel gene delivery systems.
研究领域:
生物材料
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纳米技术
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药学
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分子生物学
✓ 已验证
DOI
高影响因子
DRUG DELIVERY
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2020
·
IF 4.902
Chunyun Wang,Peilan Qi,Yan Lu,Lei Liu,Yanan Zhang,Qianli Sheng,Tianshun Wang,Mengying Zhang,Rui Wang,Shiyong Song
The Editors and Publisher of the journal Drug Delivery, have retracted the following article:Chunyun Wang, Peilan Qi, Yan Lu, Lei Liu, Yanan Zhang, Qianli Sheng, Tianshun Wang, Mengying Zhang, Rui Wang & Shiyong Song (2020) Bicomponent polymeric micelles for pH-controlled delivery of doxorubicin, Drug Delivery, 27:1, 344–357, DOI: 10.1080/10717544.2020.1726526Since publication, concerns have been raised about the integrity of the data in the article. When approached for an explanation, the authors have been unable to fully address the concerns raised. As verifying the validity of published work is core to the integrity of the scholarly record, we are therefore retracting the article. All authors listed in this publication have been informed.We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines.The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as ‘Retracted’.
研究领域:
药学
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生物材料
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肿瘤治疗
✓ 已验证
DOI
高影响因子
Nanomedicine
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2020
·
IF 4.3
Dong Shen,Yan Shen,Qian Chen,Bin Huang,Yedong Mi,Yibo Shan,Guiping Yu,Thomas J Webster
Aim: Micelles are one of the most promising nanoplatforms for drug delivery, and here, cholesterol-conjugated polyoxyethylene sorbitol oleate (CPSO) micelles have been fabricated for the pulmonary delivery of paclitaxel (PTX). Materials & methods: PTX-CPSO micelles were prepared by a dialysis-ultrasonic method, and a single-factor experiment with a Box–Behnken design was conducted to optimize the formulation. Furthermore, intracellular and phagocytosis escape studies of the optimized formulation were performed on A549 and NR8383 cells. Results: The optimal micelles exhibited satisfactory encapsulation efficiency (78.48 ± 2.36%) and drug loading (17.06 ± 1.71%). In vitro studies showed enhanced CPSO micelle A549 cellular uptake and their ability to escape macrophages. Conclusion: PTX-CPSO micelles could be a promising system for pulmonary targeting by intravenous administration. Graphical abstract:
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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肺医学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF MOLECULAR LIQUIDS
·
2020
·
IF 5.065
Zhao Chen,Danhua Xie,Binglei Song,Chaowang Li,Xiaomei Pei,Rong Li
A tetrameric monomer containing an azobenzene group (abbreviated as tetra-N(AZO)-Br) was synthesized in this paper, and a “pseudo” oligomeric surfactant was constructed using tetra-N(AZO)-Br and a traditional surfactant, sodium oleate (SO), by non-covalent bonded interaction. The synthesized tetra-N(AZO)-Br was characterized by 1 H NMR and UV–Vis spectra. The viscoelasticity and the difference in nuclear magnetic resonance (NMR) and ultraviolet (UV) absorption of the SO/tetra-N(AZO)-Br “quasi” tetrameric surfactant solution at different concentrations were investigated. The SO/tetra-N(AZO)-Br “pseudo” tetrameric surfactant could form highly viscoelastic worm-like micelles in solution, and the zero-shear viscosity of the system increased with increasing concentration. The viscoelastic properties of SO/tetra-N(AZO)-Br “pseudo” tetrameric surfactant had no obvious change after UV light irradiation . Since the combination of SO and tetra-N(AZO)-Br molecules was in dynamic equilibrium through the attraction of positive and negative charges, as much as 30% of the trans- tetra-N(AZO)-Br molecules in worm-like aggregates were transformed to their cis- structure. The un-transformed trans- tetra-N(AZO)-Br molecule could move in the aggregate and help maintain the structure of the aggregates, so that the viscosity had no obvious change.
研究领域:
化学
·
材料科学
✓ 已验证
产品关联
DOI
高影响因子
PHARMACEUTICAL RESEARCH
·
2019
·Vol. 37
·期 1
·1-17
·
IF 3.896
Zhang Zhiqiang,Yu Miao,An Tong,Yang Jun,Zou Meijuan,Zhai Yinglei,Sun Wei,Cheng Gang
Purpose The discovery of nano drug delivery system has rendered a great hope for improving cancer therapy. However, there are some inevitable obstacles that constrain its development, such as the physical and biological barriers, the toxicity of carrier materials and the physiological toxicity of drugs. Here, we report a polymeric prodrug micelle (PPM) with pH/redox dual-sensitivity, which was prepared using methoxy poly (ethylene glycol) (mPEG) with favorable biosafety to improve cancer therapy. Method The tumor microenvironment stimuli-responsive PPMs were prepared and characterized in vitro and in vivo . Results Our data displayed that the PPMs with excellent biocompatibility exhibited the stimuli-responsive drug release behavior under the microenvironment of cancer cells, superior cellular internalization and lower cytotoxicity. A new method to control drug release behavior was proposed by comparing the release behavior of PPMs formed by PEG of different molecular weight. Furthermore, the fabricated PPMs exhibited the “oral-like” blood concentration curve, improved biodistribution, reduced tissue toxicity and excellent antitumor efficiency in vivo . Consistently, these results indicated that PPMs improved chemotherapeutic efficiency and reduced side effects of the model drug doxorubicin (DOX). Conclusion The prepared pH/redox dual-sensitive PPM enhanced the chemotherapy effect on the tumor site while reducing the physiological toxicity of DOX.
Graphical Abstract
研究领域:
药剂学
·
肿瘤学
·
生物材料学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2020
·
IF 2.734
Longgui Zhang,Yuji Pu,Junhua Li,Jianqin Yan,Zhongwei Gu,Wenxia Gao,Bin He
Polymer-small molecule conjugates could act as drug carriers to load hydrophobic antineoplastics by π-π interactions. However, weak hydrophobicity would lead to limited drug loading capacity and stability in blood circulation. Herein, we used the graft strategy to significantly increase the hydrophobicity for improving drug loading capacity and microenvironment stimuli characteristics. Coumarin and imidazole were grafted to biodegradable and biocompatible poly(ethylene glycol)- b -poly( l -lysine) (PEG-PLL), respectively, endowing strong hydrophobicity for efficient drug loading and pH-responsiveness for controlled drug release . The critical micelle concentration of mPEG-PLL- g -COU/IMZ could be as low as 9.49 × 10 −6 mol/L. Anticancer drug doxorubicin (DOX) was used as a model drug and COU-grafted polymers showed high drug loading contents of ~17%. The π-π interactions between DOX and COU were established by UV and fluorescence spectroscopy. The pH-sensitive and COU-grafted polymeric micelles showed enhanced in vitro anticancer efficacy, due to the high drug loading capacity, faster cellular uptake, and pH-responsive drug release. This study indicated that stimuli-responsive, aromatic small molecule-grafted polymeric micelles could be a promising platform for efficient drug delivery and cancer therapy, due to their high drug loading capacity and controlled drug release.
研究领域:
药剂学
·
材料科学
·
肿瘤学
✓ 已验证
产品关联
DOI
高影响因子
International Journal of Nanomedicine
·
2020
·
IF 5.115
Hao Zhou,Zhiwen Qi,Xingying Xue,Chengzhang Wang
Purpose The aim of this study was to develop a means of improving the bioavailability and anticancer activity of urushiol by developing an urushiol-loaded novel tumor-targeted micelle delivery system based on amphiphilic block copolymer poly(ethylene glycol)-b-poly-(β-amino ester) (mPEG-PBAE).Materials and Methods We synthesized four different mPEG-PBAE copolymers using mPEG-NH2 with different molecular weights or hydrophobicity levels. Of these, we selected the mPEG5000-PBAE-C12 polymer and used it to develop an optimized means of preparing urushiol-loaded micelles. Response surface methodology was used to optimize this formulation process. The micellar properties, including particle size, pH sensitivity, drug release dynamics, and critical micelle concentrations, were characterized. We further used the MCF-7 human breast cancer cell line to explore the cytotoxicity of these micelles in vitro and assessed their pharmacokinetics, tissue distribution, and antitumor activity in vivo.Results The resulting micelles had a mean particle size of 160.1 nm, a DL value of 23.45%, and an EE value of 80.68%. These micelles were found to release their contents in a pH-sensitive manner in vitro, with drug release being significantly accelerated at pH 5.0 (98.74% in 72 h) without any associated burst release. We found that urushiol-loaded micelles were significantly better at inducing MCF-7 cell cytotoxicity compared with free urushiol, with an IC50 of 1.21 mg/L. When these micelles were administered to tumor model animals in vivo, pharmacokinetic analysis revealed that the total AUC and MRT of these micelles were 2.28- and 2.53-fold higher than that of free urushiol, respectively. Tissue distribution analyses further revealed these micelles to mediate significantly enhanced tumor urushiol accumulation.Conclusion The pH-responsive urushiol-loaded micelles described in this study may be ideally suited for clinical use for the treatment of breast cancer.
研究领域:
药剂学
·
肿瘤学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF SURFACTANTS AND DETERGENTS
·
2019
·Vol. 22
·期 3
·587-595
·
IF 1.672
Mingwei Zhao,Zhibin Gao,Caili Dai,Xin Sun,Yue Zhang,Xiujie Yang,Yining Wu
Enhancing the viscoelastic properties of wormlike micelles by adding nanoparticles has been widely reported. Various mechanisms have been proposed to explain how nanoparticles strengthen the network formed by wormlike micelles. It remains unclear whether nanoparticles produce the same effect on systems with different entanglement degrees. To clarify this issue, the concentration of potassium chloride was used to control the entanglement degree of wormlike micelles. The rheological behavior of different nanoparticle-enhanced wormlike micellar systems (NEWMS) was investigated using rheology. Three critical parameters including zero-shear viscosity ( η 0 ), relaxation time ( τ R ), and contour length ( L ) were calculated to analyze the effect of nanoparticles on the different wormlike micellar systems. An appropriate mechanism describing the interaction between nanoparticles and wormlike micelles with different structures was proposed.
研究领域:
化学
·
材料科学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）