RSC Advances
·
2018
·Vol. 8
·期 35
·19642-19650
·
IF 2.936
Fancui Meng,Zhuangzhuang Qiao,Yan Yao,Jianbin Luo
Polyurethane with pendant azide groups on the soft segment (PU-GAP) was prepared in this study to further increase the content of reactive azide groups and improve their surfaces enrichment for further functionalization. Polymer diols with pendant azide groups (GAP) were prepared by transforming the pendant chlorine groups at polyepichlorohydrin (PECH) into azide groups with sodium azide. The prepared PECH, GAP and PU-GAP was characterized by GPC, 1H NMR and FTIR. Propargylic mPEG (mPEG-alkyne) was used as model surface modification reagents which was grafted on the prepared azido containing polyurethane films via click chemistry. The surface morphology, chemical composition and wettabilities were studied by SEM, XPS and water contact angle (WCA) analysis, respectively. SEM results demonstrated different surface topologies between mPEG modified PU surface and original PU surface. XPS and WCA analysis proved the successful grafting of mPEG on the pendant azide groups of PUs. The mPEG modified PU surfaces demonstrated good antifouling activities against model bacteria and mPEG with larger molecular weights modified surfaces showed better resistance efficiency to attachment of bacteria. Therefore, the surface reactive polyurethane we prepared can be a universal platform for further functionalization according actual applications.
研究领域:
材料科学
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生物医学工程
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2014
·
IF 3.785
Qian Li,Shixian Lv,Zhaohui Tang,Muhua Liu,Dawei Zhang,Yan Yang,Xuesi Chen
Herein, we develop a co-delivery system of paclitaxel (PTX) and doxorubicin hydrochloride (DOX·HCl) based on methoxypoly(ethylene glycol)- block -poly( l -glutamic acid) (mPEG- b -PLG) for cancer treatment. PTX was grafted to the mPEG- b -PLG by esterification to give mPEG- b -PLG- g -PTX. DOX·HCl was encapsulated via electrostatic interaction and hydrophobic stack between the DOX·HCl and mPEG- b -PLG- g -PTX in aqueous solution. The release rate of DOX·HCl from the drug-loaded nanoparticles (mPEG- b -PLG- g -PTX-DOX) was slow at blood pH (pH 7.4), but obviously increased at endosome pH (pH 5.4). The mPEG- b -PLG- g -PTX-DOX exhibited slight synergistic effect in inhibition of proliferation of A549 and MCF-7 human cancer cells. For in vivo treatment of xenograft human breast tumor (MCF-7), the mPEG- b -PLG- g -PTX-DOX nanoparticles exhibited remarkable tumor inhibition effect with a 95.5% tumor-suppression-rate which was significantly higher than those of related single anticancer agents such as free DOX·HCl and mPEG- b -PLG- g -PTX. These results indicated that the mPEG- b -PLG- g -PTX-DOX would have great potential in cancer therapy.
研究领域:
药剂学
·
肿瘤学
·
生物医学工程
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DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2017
·
IF 3.887
Fuqiang Guo,Jiajia Shang,Hai Zhao,Kangrong Lai,Yang Li,Zhongxiong Fan,Zhenqing Hou,Guanghao Su
As one of nanomedicine delivery systems (NDSs), drug nanocrystals exhibited an excellent anticancer effect. Recently, differences of internalization mechanisms and subcellular localization of both drug nanocrystals and small molecular free drug have drawn much attention. In this paper, paclitaxel (PTX) as a model anticancer drug was directly labeled with 4-chloro-7-nitro-1, 2, 3-benzoxadiazole (NBD-Cl) (a drug-fluorophore conjugate Ma et al. (2016) and Wang et al. (2016) [1,2] (PTX-NBD)). PTX-NBD was synthesized by nucleophilic substitution reaction of PTX with NBD-Cl in high yield and characterized by fluorescence, XRD, ESI–MS, and FT-IR analysis. Subsequently, the cube-shaped PTX-NBD nanocrystals were prepared with an antisolvent method followed by surface functionalization of SPC and MPEG-DSPE. The obtained specific shaped [email protected] NCs had a hydrodynamic particle size of ∼50 nm, excellent colloidal stability, and a high drug-loading content of ∼64%. Moreover, in comparison with free PTX-NBD and the sphere-shaped PTX-NBD nanocrystals with surface functionalization of SPC and MPEG-DSPE ( [email protected] NSs), [email protected] NCs remarkably reduced burst release and improved cellular uptake efficiency and in vitro cancer cell killing ability. In a word, the work highlights the potential of theranostic prodrug nanocrystals based on the drug-fluorophore conjugates for cell imaging and chemotherapy.
研究领域:
药学
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纳米技术
·
癌症研究
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DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
·
2020
·
IF 3.616
Jiahui Sun,Jing Li,Qi Liu,Min Jiang,Mengjia Yang,Siwen Zhan,Tong Qiu,Kaiyong He,Xueqiong Zhang
This study aimed to develop, evaluate, and optimize the mPEG-PLA/vitamin E-TPGS mixed micelle drug delivery system to encapsulate celecoxib (CXB) and honokiol (HNK) for intravenous treatment of breast cancer. To this end, we formulated CXB-loaded mPEG-PLA/vitamin E-TPGS (PV-CXB) and HNK-loaded mPEG-PLA/vitamin E-TPGS (PV-HNK) mixed micelles and analyzed their characteristics. The 4T1 cell line was used for cytotoxicity determination and cellular uptake experiments, and for establishing a 4T1-bearing mouse model for histopathology, immunofluorescence, terminal deoxynucleotidyl transferase-mediated nick end labeling, and Western blot analysis . The synergistic effects of PV-CXB and PV-HNK combination therapy were investigated in vitro and in vivo using the coefficient of drug interaction values. The mean size of PV-CXB and PV-HNK prepared with optimal formulation was approximately 50 nm , with a spherical shape. PV-CXB and PV-HNK combination therapy exhibited cytotoxicity in 4T1 cells in vitro. However, the toxicity of PV-CXB and PV-HNK combination therapy was not apparent in normal tissues (heart, liver, spleen, lung, and kidney) in vivo and reduced the expression of collagen fibers in tumor tissues. Moreover, the combination therapy reduced the expression of tumor growth biomarkers (Foxp3, CD4, Gr-1, CD11b, CD31, Ki67, FoxM1, and VEGF). In addition, the tumor cell apoptosis rate reached 45.71 ± 0.62%. The combined treatment with PV-CXB and PV-HNK showed synergistic effect both in vitro and in vivo. Thus, the PV-CXB and PV-HNK drug delivery system could be used as a potential combination therapy for breast cancer .
研究领域:
药剂学
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肿瘤学
·
生物医学工程
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产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2016
·
IF 3.902
Huiyuan Zhang,Kaiming Wang,Pei Zhang,Wenxiu He,Aixin Song,Yuxia Luan
Docetaxel (DTX) can produce anti-tumor effects by inhibiting cell growth and inducing apoptosis. However, the poor solubility of DTX restricts its application and its clinical formulation has caused serious adverse reaction due to the use of Tween-80. In the present study, DTX was conjugated to an amphiphilic di-block polymer to solve these problems. Methoxy poly(ethylene glycol)-poly(ε-caprolactone) (mPEG-PCL) was selected as the polymer skeleton and a redox sensitive disulfide bond was used as the linker between DTX and mPEG-PCL. The synthesized mPEG-PCL-SS-DTX conjugates were characterized by 1 H-nuclear magnetic resonance ( 1 H NMR) and Fourier transform infrared spectroscopy (FTIR). Interestingly, the mPEG-PCL-SS-DTX conjugates could self-assemble into micelles in aqueous solution. The critical micelle concentration (CMC) of mPEG-PCL-SS-DTX micelles was about 2.3 mg L −1 determined using pyrene molecule fluorescent probe method while the size of mPEG-PCL-SS-DTX micelles was determined to be ca . 17.6 nm and 116.0 nm with a bimodal distribution by dynamic light scattering (DLS). The in vitro release results indicated that the as-prepared micelles exhibited a sustained release profile with good redox sensitive properties. In particular, the hemolytic toxicity test indicated the as-prepared mPEG-PCL-SS-DTX micelles had negligible hemolytic activity, demonstrating their safety in drug delivery system. Cytotoxicity assay of the mPEG-PCL-SS-DTX micelles verified their highly enhanced cytotoxicity to MCF-7/A and A549 cells. These results thus demonstrated that the present redox-sensitive mPEG-PCL-SS-DTX micelle was an efficient and safe sustained drug delivery system in the biomedical area.
研究领域:
药剂学
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肿瘤学
·
生物医学工程
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DOI
高影响因子
RSC Advances
·
2016
·Vol. 6
·期 17
·13698-13709
·
IF 3.289
Ying Hao,YiXing Huang,YunQi He,JinRong Peng,LiJuan Chen,Xun Hu,ZhiYong Qian
In this study, we successfully prepared MPEG–PDLLA polymer micelles with two different particle sizes, A and B. DLS and TEM assays demonstrated that the particle sizes of the polymer micelles A and polymer micelles B were about 25 nm and 150 nm respectively. The stability of the MPEG–PDLLA polymer micelles in vitro revealed that the free Cy5.5 dye had been successfully loaded into the polymer micelles as a fluorescence marker and the fluorescence wasn’t quenched until 72 h. The cellular uptake of the polymer micelles was time-dependent and micelles A (particle size 25 nm) showed a higher efficiency to be internalized into the cytoplasm of MCF-7 cells than micelles B (particle size 150 nm). Furthermore, in vivo and in vitro biodistribution and tumor-targeting of polymer micelles MPEG–PDLLA were investigated in female MCF-7 tumor-bearing balb/cA-nu mice with an IVIS imaging system. The results showed that polymer micelles A (particle size 25 nm) had a time dependent biodistribution and tumor site accumulation in mice bearing MCF-7 tumors. Meanwhile, the NIR fluorescence intensity of polymer micelles B (particle size 150 nm) in tumor sites showed a pattern of a rise, a peak and then a decline. What’s more, the distribution of the polymer micelles in the tissue slices demonstrated the same results. Consequently, the results indicated that the micelles with a smaller particle size (25 nm) could be more efficiently internalized into cells and increase the enhanced permeation and retention (EPR) effect in tumor tissue. Therefore, a reasonable small size of micelles may be a key factor for a high-performance anti-cancer drug delivery system.
研究领域:
药剂学
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肿瘤学
·
生物医学工程
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产品关联
DOI
高影响因子
Materials Science & Engineering C-Materials for Biological Applications
·
2018
·
IF 5.08
Jiru Jia,Chaoxia Wang
High water absorption aerogels with three-dimensional porous structures and high specific surface areas have been fabricated from methoxy polyethylene glycol‑polycaprolactone block copolymer (mPEG‑PCL) via a facile approach by electrospinning, mechanical homogeneous shearing and dispersing short fibers in the water, freeze-drying, and heat crosslinking. The three-dimensional nanofiber aerogels (TNAs) exhibit continuous porous structures which are restructured with crisscrossed and dispersed nanofibers. The aerogel displays a low density (36 ± 3 mg/cm 3 ), a high specific surface area (230 m 2 /g), a high pore volume (5.9 cm 3 /g), a high porosity of 85% as well as an average pore diameter (1.12 μm). The as-made mPEG-PCL TNAs deliver a high average water-absorption capacity of 24.11 g/g and a good retention ability owing to the three-dimensional porous structures and large micropores population. The water absorption could still reach approximately 25 g/g after 10 compression cycles of TNAs. The average dehydration weight loss of 3.1% demonstrates that the materials are hardly soluble in the water, and the structural characteristic would not be changed after water adsorption. The antimicrobial activity against the bacteria Staphylococcus aureus and Escherichia coli are assessed that the TNAs are suitable carriers of antimicrobial agents. Moreover, as showed by cytotoxic tests, the TNAs are neglectable toxic, which are suitable for applications in environmental bioengineering. Based on the high water absorption and biocompatibility, the TNAs could be suitable candidates for health care materials and medical products.
研究领域:
材料科学
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生物医学工程
·
环境工程
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DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2023
·
IF 8
Kai Dong,Yan Yan,Pengchong Wang,Xianpeng Shi,Lu Zhang,Ke Wang,Jianfeng Xing,Yalin Dong
In this study, a type of multifunctional mixed micelles were prepared by a novel biodegradable amphiphilic polymer (MPEG-SS-2SA) and a multidrug resistance (MDR) reversal agent (d-α-tocopheryl polyethylene glycol succinate, TPGS). The mixed micelles could achieve rapid intracellular drug release and reversal of MDR. First, the amphiphilic polymer, MPEG-SS-2SA, was synthesized through disulfide bonds between poly (ethylene glycol) monomethyl ether (MPEG) and stearic acid (SA). The structure of the obtained polymer was similar to poly (ethylene glycol)-phosphatidylethanolamine (PEG-PE). Then the mixed micelles, MPEG-SS-2SA/TPGS, were prepared by MPEG-SS-2SA and TPGS through the thin film hydration method and loaded paclitaxel (PTX) as the model drug. The in vitro release study revealed that the mixed micelles could rapidly release PTX within 24 h under a reductive environment because of the breaking of disulfide bonds. In cell experiments, the mixed micelles significantly inhibited the activity of mitochondrial respiratory complex II, also reduced the mitochondrial membrane potential, and the content of adenosine triphosphate, thus effectively inhibiting the efflux of PTX from cells. Moreover, in the confocal laser scanning microscopy, cellular uptake and 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl-tetrazolium bromide assays, the MPEG-SS-2SA/TPGS micelles achieved faster release and more uptake of PTX in Michigan Cancer Foundation-7/PTX cells and showed better antitumor effects as compared with the insensitive control. In conclusion, the biodegradable mixed micelles, MPEG-SS-2SA/TPGS, could be potential vehicles for delivering hydrophobic chemotherapeutic drugs in MDR cancer therapy.
研究领域:
药剂学
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肿瘤学
·
生物材料科学
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产品关联
DOI
PubMed
高影响因子
Drug Delivery and Translational Research
·
2017
·Vol. 8
·期 1
·83-96
·
IF 3.094
Pan Linmei,Zhou Jing,Ju Feng,Zhu Huaxu
Alpha-asarone is a bioactive component of Acorus tatarincuii Schott with low bioavailability, which is often used for treatments of various brain diseases in clinical setting. This study was to formulate biodegradable methoxy polyethylene glycol-polylactic acid (mPEG-PLA) nanoparticles (NPs) surface-modified by lactoferrin (Lf), for delivering α-asarone into the brain following intranasal administration. Alpha-asarone NPs were prepared by premix membrane emulsification. The relative parameters were optimized by a Box-Behnken experimental design. The particle size, zeta potential, and dispersibility index of NPs and Lf-NPs were characterized. Their ex vivo permeation, pharmacokinetics, distribution in the brain and other tissue, brain targeting, and toxicity were investigated. Following intranasal administration, Lf-NPs had a better permeability and no significant poor bioavailability compared to NPs; the area under curve from 0 to 12 h of α-asarone in Lf-NPs of the olfactory bulb, hippocampus, olfactory bundles, and thalamus were 2.14-, 4.17-, 3.62-, and 1.96-fold of those in NP group, respectively. Lactoferrin could enhance the efficacy of brain targeting with NPs and reduce its liver accumulation. Toxicity of NPs on nasal mucosal cilia and epithelial cells was also decreased by Lf. To summarize, these results demonstrate that Lf-NPs of α-asarone have potential as a carrier for nose-to-brain delivery of α-asarone for brain diseases.
研究领域:
药剂学
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神经科学
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生物医学工程
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DOI
PubMed
高影响因子
Carbohydrate Polymer Technologies and Applications
·
2021
·
IF 0
Renliang Lyu,Zeqin Li,Cheng Liang,Cheng Zhang,Ting Xia,Ming Wu,Yi Wang,Lichun Wang,Xiaogang Luo,Caili Xu
In this work, due to its excellent adsorption performance, biodegradability, and low toxicity, chitosan was used as the raw material to synthesize a series of new oil-in-water (O/W) type crude oil demulsifiers. First, an acyl group was introduced onto the chitosan molecule. Then, sodium chloroacetate was used as a carboxymethylation reagent to introduce a carboxymethyl group into the acylated chitosan. Furthermore, polyethylene glycol monomethyl ether with an average molecular weight of 1900 (MPEG-1900) was used to react with acylated carboxymethyl chitosan to synthesize chitosan-based O/W type demulsifiers. The molecular structures of the synthetic chitosan derivatives were characterized using Fourier-transform infrared spectroscopy (FTIR) and 1 H nuclear magnetic resonance techniques. The results showed that the surface tension decreased with an increase in the concentration of polysaccharide demulsifiers, which included MPEG-1900-A 4 CMC, MPEG-1900-A 6 CMC, and MPEG-1900-A 8 CMC. The demulsification efficiency of these synthetic demulsifiers reached a maximum over 100 min at a concentration of 200 ppm at 50 °C. The as-synthesized chitosan derivatives showed good demulsification performance.
研究领域:
化学工程
·
材料科学
·
环境科学
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DOI
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2016
·
IF 3.994
Dujuan Zhao,Huiyuan Zhang,Shengfeng Yang,Wenxiu He,Yuxia Luan
The main cause of multidrug resistance (MDR) is overexpression of active efflux transporters, such as P-glycoprotein (P-gp). To reverse MDR and improve the chemotherapy effect of paclitaxel (PTX), we propose a new drug delivery system based on mixed micelles constructed with d -α-tocopheryl poly(ethylene glycol) 1000 succinate (TPGS) and the mPEG-SS-PTX conjugate with consideration that TPGS is a P-gp inhibitor that can block the cancer cell action of pumping drugs outside of cells and can enhance the anticancer effect. mPEG-SS-PTX is synthesized by conjugating hydrophilic mPEG with a hydrophobic drug, PTX, via a redox-sensitive disulfide bond. The mPEG-SS-PTX conjugate is amphiphilic and can self-assemble in water. Mixed micelles formed by the mPEG-SS-PTX conjugate and TPGS have a low critical micelle concentration (CMC, ∼1.05 × 10 −3 mg/mL) and high drug loading content (∼19.6%). The disulfide bond in the mPEG-SS-PTX conjugate can be broken in cancer cells (a reductive environment) and release PTX to kill cancer cells. In vitro cytotoxicity and cell uptake suggest that mixed micelles can effectively improve the accumulation of PTX in multidrug-resistant MCF-7 cells. Therefore, the present as-prepared mixed micelles very effectively reverse the MDR and enhance the therapeutic effect.
研究领域:
药学
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纳米技术
·
癌症研究
·
药物递送系统
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产品关联
DOI
PubMed
高影响因子
Frontiers in Veterinary Science
·
2025
·
IF 2.9
Yanling Sun,Yanan Mao,Xin He,Xinghua Zhao
The aim of this study was to prepare polymeric micelles composed of enrofloxacin (ENR) and methoxy poly (ethylene glycol)-poly(lactide) (mPEG-PLLA) using a solvent evaporation method to overcome the solubility-limited oral bioavailability of ENR. The formulation was optimized using a Box–Behnken design (BBD) to obtain ENR polymeric micelles (ENR-m) with high drug loading (DL, %) and entrapment efficiency (EE, %). The physicochemical properties, in vitro drug release, pharmacokinetics, and antibacterial efficacy were evaluated in comparison to pure ENR. ENR-m was successfully prepared and demonstrated satisfactory drug loading (68.38 ± 0.22%), entrapment efficiency (88.40 ± 0.91%), particle size (PS) (133.67 ± 3.10 nm), and polydispersity index (PDI) (0.13 ± 0.03). The ENR-m also exhibited excellent stability under environmental conditions (40°C and 75% relative humidity (RH)). In vitro release of ENR from micelles was accelerated in a PBS solution. A pharmacokinetic study on beagles revealed that the oral bioavailability of ENR-m was enhanced by approximately 1.60-fold compared to pure ENR (p < 0.01) and by 1.66-fold compared to commercially available tablets of ENR (p < 0.01). The antibacterial activity of ENR-m against Escherichia coli (E. coli) and Salmonella typhi (S. typhi) was stronger than that of pure ENR.
研究领域:
药剂学
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药理学
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微生物学
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高分子科学
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药物传递
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）