Polymer Chemistry
·
2022
·Vol. 13
·期 20
·2964-2970
·
IF 5.364
Ying Wang,Peng Chen,Qiaojie Luo,Xiaodong Li,Weipu Zhu
Polymeric prodrugs have attracted great interest in the field of anticancer drug delivery owing to their integrated advantages of prodrugs and nanoparticles. However, the ambiguous chemical composition of polymeric prodrugs is still a major obstacle to their clinical applications. In this study, an amphiphilic poly(ethylene glycol) derivative with multiple thiols was first synthesized on a large scale through the melt co-polycondensation of oligo(ethylene glycol), 1,4-butanediol and mercaptosuccinic acid. Then an adamantane modified doxorubicin (DOX) with a pH-sensitive hydrazone bond and a β-cyclodextrin derivative with multiple acryloyls were precisely synthesized. Finally, novel supramolecular polymeric prodrug (SPP) micelles with a precise drug molecular structure and drug loading content were facilely prepared using the above three components via simultaneous self-assembly, a thiol–ene “click” reaction and a host–guest supramolecular interaction in water. The resultant pH-sensitive SPP micelles with a stable core-crosslinked structure and strong drug “bonding” show long blood circulation time, effective cellular uptake and fast DOX release in tumor cells, which significantly improved the antitumor efficacy and security compared with free DOX. This work established a promising drug delivery platform for cancer chemotherapy.
研究领域:
药剂学
·
化学
·
肿瘤学
✓ 已验证
DOI
高影响因子
CHINESE JOURNAL OF POLYMER SCIENCE
·
2014
·Vol. 32
·期 10
·1413-1418
·
IF 1.42
Li Hua-jie,Yu Zhong,Wang Shuang-ping,Zhang Li-ming,Yang Li-qun
Photosensitizer (photosan)-encapsulated micelles were prepared by self-assembly of Photosan with two amphiphilic polysaccharide derivatives, including the cholesteryl conjugated sodium alginate derivative (CSAD) and the deoxycholic acid group conjugated chitosan derivative (DA-Chit). The results of UV-Vis and fluorescence spectroscopy indicated that the hydrogen bonding strength dominated the micelle formation. Methyl viologen was used as a model quencher of photosan. Using the steady-state fluorescence technology, the quenching constants were determined to be 2.05, 1.88 and 0.30 L/mmol for the free photosan, the photosan-CSAD micelle and the photosan-DA-Chit micelle, respectively. This suggested that photosan was protected from quenching of methyl viologen by the polysaccharide micelles. In addition, the protection effect of the photosan-DA-Chit micelle was significantly stronger than that of the photosan-CSAD micelle. The photosan-DA-Chit micelle is thus anticipated for protection of photoactivity of photosan during the blood circulation process in vivo .
研究领域:
药剂学
·
生物化学
✓ 已验证
DOI
高影响因子
BIOMATERIALS
·
2019
·
IF 10.273
Qian-Qian Fan,Cheng-Lu Zhang,Jian-Bin Qiao,Peng-Fei Cui,Lei Xing,Yu-Kyoung Oh,Hu-Lin Jiang
As hepatic stellate cells (HSCs) are essential for hepatic fibrogenesis , HSCs targeted nano-drug delivery system is a research hotspot in liver fibrosis therapy. However, the excessive deposition of fibrosis collagen (mainly collagen I) in the space of Disse associated with hepatic fibrogenesis would significantly hinder nano-formulation delivery to HSCs. Here, we have prepared a collagenase I and retinol co-decorated polymeric micelle that possess nanodrill-like and HSCs-target function based on poly-(lactic-co-glycolic)-b-poly (ethylene glycol)-maleimide (PLGA-PEG-Mal) (named CRM) for liver fibrosis therapy. Upon encountering collagen I barrier, CRM exerted a nanodrill-like function, efficiently degrading pericellular collagen I and showing greater uptake by human HSCs than other micelle formulations. Besides, CRM could realize excellent accumulation in the fibrotic liver and accurate targeting to activated HSCs in mouse hepatic fibrosis model. Moreover, CRM loaded with nilotinib (CRM/NIL), a second-generation tyrosine kinase inhibitor used in the treatment of liver fibrosis, showed optimal antifibrotic activity. This work suggests that CRM with dual function is an efficient carrier for liver fibrosis drug delivery and collagenase I decorating could be a new strategy for building more efficient HSCs targeted nano-drug delivery system.
研究领域:
药学
·
纳米技术
·
肝病学
·
药物递送系统
✓ 已验证
DOI
PubMed
高影响因子
RSC Advances
·
2016
·Vol. 6
·期 64
·58871-58883
·
IF 3.289
Yangmiao Mo,Shudong Lin,Yuanyuan Tu,Guojun Liu,Jiwen Hu,Feng Liu,Jun Song
A novel amphiphilic binary graft copolymer poly(glycidyl methacrylate)-graft-[poly(2-cinnamoyl-oxyethyl methacrylate)-random-methoxy polyethylene glycol] (PGMA-g-(PCEMA-r-MPEG)) was successfully synthesized by a combination of atom transfer radical polymerization (ATRP) and click reaction, in which alkyne-end-functionalized poly(2-cinnamoyloxyethyl methacrylate) (PCEMA–CCH) and poly(ethylene glycol) methyl ether (MPEG–CCH) were grafted onto a poly(3-azide-2-hydroxy-propyl methacrylate) (P(GMA-N3) backbone. This polymer was used to prepare stable unimolecular micelles (UMMs), which could be produced using either high or low polymer concentrations. Since water is a good solvent only for MPEG but a poor solvent for both PGMA and PCEMA, the hydrophobic PGMA and PCEMA segments aggregated together to form a dense core that was surrounded by a corona based on the soluble MPEG segments. PCEMA was photo-crosslinkable, and thus the UMMs could be crosslinked by shining UV light on the system to yield permanent UMMs. The morphologies of the UMMs were characterized by TEM, AFM, and DLS. Both the TEM and AFM observations indicated that the crosslinked UMMs had a diameter of ∼13 nm, while the DLS measurements indicated they had a diameter of ∼34 nm. The unimolecular state of the micelles was confirmed by SEC, as well as a comparison of the theoretical mass per graft copolymer molecule with that of an individual micelle. Moreover, the morphology of the UMMs was unperturbed by the crosslinking reaction although they became more compact and had a slightly smaller diameter.
研究领域:
高分子科学
·
纳米技术
·
材料化学
·
胶体与界面科学
✓ 已验证
DOI
高影响因子
RSC Advances
·
2018
·Vol. 8
·期 1
·380-389
·
IF 2.936
Dongyang Tang,Xin Zhao,Tie Yang,Cheng Wang
An effective chemotherapy is usually subject to an insufficient loading of hydrophobic drugs as well as severe side effects. In order to address these dilemmas in one formulation, we herein construct paclitaxel prodrug based mixed micelles (MMs) for tumor-targeted chemotherapy. The paclitaxel prodrug containing a hydrophobic PTX and a hydrophilic PEG chain can self-assemble into uniform MMs with distearoyl phosphoethanolamine–polyethylene glycol–folate (DSPE–PEG–FA). The resultant MMs with preferable stability and hemolysis compatibility could improve the cellular uptake of nanoparticles via FA receptor-mediated endocytosis as compared to the single micelles (SMs). This tumor targetability was also confirmed in vivo by fluorescent imaging. MMs with a stable drug loading as well as tumor targetability displayed elevated in vitro cytotoxicity and in vivo antitumor efficacy compared with Taxol, which could be a potential formulation for cancer therapy.
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
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2013
·
IF 3.554
Dong Li,Yan Liang,Yusi Lai,Gang Wang,Bin He,Zhongwei Gu
The aim of this study was to develop a new polymeric micelle delivery system for antitumor drugs . An amphiphile of methoxypoly(ethylene glycol)-histidine-di(cinnamic acid) (PEGHC) with a small lipophilic moiety instead of a hydrophobic biodegradable polymer chain was synthesized and characterized. The PEGHC self-assembled into micelles. The critical micelle concentration (CMC) was tested. 9-Nitro-20(s)-camptothecin (9-NC) was used as a model drug for encapsulation. The size and morphology of both blank and 9-NC loaded micelles were characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The release profile of 9-NC loaded micelles was studied. HepG2 liver cancer cells were incubated with the drug-loaded micelles to investigate the in vitro anticancer efficiency. The results showed that the 9-NC loaded micelles exhibited high accumulated release rate (>85%) and efficient in vitro anticancer activity .
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
RSC Advances
·
2014
·Vol. 4
·期 16
·8165-8176
·
IF 3.708
Yongyong Li,Xue Lei,Haiqing Dong,Tianbin Ren
In this work, sheddable, degradable, cationic micelles were designed and developed based on intermediate disulfide-linked poly(ε-caprolactone)-b-poly(N,N-dimethylamino-2-ethylmethacrylate) (PCL-SS-PDMA) diblock copolymers, for glutathione (GSH)-mediated intracellular delivery of anticancer drug doxorubicin (DOX) and gene. The PCL-SS-PDMA diblock polymers with different PDMA block lengths were prepared by a combination of ring opening polymerization (ROP) and atom transfer radical polymerization (ATRP). Driven by hydrophobic interaction, these polymers self-assembled into nanoscaled micelles with size ranging from 70 to 200 nm, and positive surface charges from +24 to +37 mV. The PDMA length was found to determine the surface charge and in turn affect the physiochemical properties and cumulative drug release. More importantly, glutathione mediated intracellular drug release was observed by intracellular fluorescence arising from DOX for the GSH treated cells. The accelerated drug release was induced by the structural disassembly after disulfide cleavage. The PCL-SS-PDMA block polymers exhibited high DNA binding affinity and cellular uptake efficiency. The gene transfection efficiency of PCL-SS-PDMA/DNA complex showed relatively low transfection efficiency in 293 T and HeLa cells, compared to PEI 25K. However, the transfection efficacy dramatically outperformed PEI 25K in human oral carcinoma cell lines (KB and CAL-27 cells). A ten-fold population of the transfected cells was found for the PS-SS-PDMA polymer, compared with PEI. The experimental results show the great potential of the new micelles in gene and drug delivery for cancer therapy.
研究领域:
药剂学
·
材料科学
·
生物医学工程
·
癌症治疗
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF MOLECULAR LIQUIDS
·
2019
·
IF 4.561
Xiaoxi Yu,Zhi Yang,Hao Li,Ruoyu Wang,Jingping Liu,Yining Wu
A novel CO 2 responsive self-assembled surfactants system was prepared using N - [3 - (dimethylamino) propyl] docosanamide (NDPD) and sodium salicylate (NaSal). Rheological measurements were performed to study the phase behaviors of NDPD/NaSal system. It was found that gels and wormlike micelles can be formed in the NDPD/NaSal system. The phase behaviors were found to be influenced by changing temperature or by involving different anions. Through increasing the temperature, gels can transform to wormlike micelles . When HCl and CO 2 were used to adjust pH, NDPD/NaSal system performed decidedly different rheological behaviors at the same pH. By theoretical calculation, it was found that the binding energy between NDPD and Cl − is larger than that of NDPD and HCO 3 − , indicating a stronger shielding ability of Cl − ions. Due to the weakened electrostatic repulsion interactions, the internal structure of NDPD/NaSal switchable system wrapped more tightly through adding HCl compared with adding CO 2 .
研究领域:
化学
·
材料科学
·
胶体与界面化学
✓ 已验证
产品关联
DOI
高影响因子
International Journal of Nanomedicine
·
2023
·
IF 8
Lan Tang,Wenhui Jiang,Lan Wu,Xiaolan Yu,Zheng He,Weiguang Shan,Lulu Fu,Zhenhai Zhang,Yunchun Zhao
Background Doxorubicin (DOX) is an anthracycline antibiotic that inhibits the growth of several solid and hematologic malignant tumors. Increasing the targeting ability of DOX and reducing the multi-drug resistance (MDR) of tumor cells to DOX are major aims for researchers.Purpose In this study, to increase therapeutic efficiency, reduce the side effects and the MDR of tumor cells to DOX, D-alpha-tocopheryl polyethylene glycol 2000 succinate monoester (TPGS2000)-DOX prodrug micelles were developed by grafting DOX to TPGS2000 via an amide bond that release DOX in the slightly acidic conditions in tumor tissue.Materials and Methods The TPGS2000-DOX micelles were constructed using polyethylene glycol 12-hydroxy stearate (Solutol HS15) as the carrier. The in vitro drug release profile and dilution stability of the nanomicelles were determined. The in vitro cytotoxicity and distribution of the nanomicelles in the tumor cells were also investigated. Moreover, we explored the therapeutic outcomes using the MCF-7/ADR tumor-bearing murine model.Results The average particle size was approximately 30 nm with a narrow distribution, which was conducive for solid tumor accumulation. The results of in vivo imaging and in vitro cellular uptake assays demonstrated that the TPGS2000-DOX micelles increased the tumor-targeting ability and cellular uptake of DOX. The anticancer potential of TPGS2000-DOX micelles was higher than that of DOX, as revealed by in vitro cytotoxic assays with MCF-7/ADR cells and in vivo antitumor assays with MCF-7 tumor-bearing nude mice.Conclusion TPGS2000-DOX prodrug micelles reverse the MDR of tumor cells, achieve passive targeting by forming nanomicelles, and subsequently enhance the efficacy and reduce the toxicity of DOX.
研究领域:
药学
·
肿瘤学
·
纳米技术
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOPARTICLE RESEARCH
·
2018
·Vol. 20
·期 10
·1-11
·
IF 2.127
Feng Runliang,Deng Peizong,Zhou Feilong,Feng Sijia,Song Zhimei
To overcome honokiol’s poor water solubility and investigate its antifungal activity and pharmacokinetic property, Pluronic® F-127 (F127)-cyclodextrin conjugate was synthesized and employed to prepare honokiol-loaded micelles through emulsion-solvent evaporation method. The drug-loaded micelles were obtained with 92.30 ± 3.28% of encapsulation efficiency being higher than that obtained from F127 due to additional cyclodextrin inclusion. Fourier transformation infrared spectrometry and diffraction scanning calorimetry analysis tests demonstrated that honokiol was successfully encapsulated into the conjugate micelles in the amorphous or solid solution state because of their interactions. Meanwhile, in vitro antifungal activity experiment indicated that the MIC 90 of drug-loaded micelles was 64 μg/mL, showing the same antifungal activity as pure honokiol although it obviously retarded honokiol’s release. In vivo pharmacokinetic results confirmed that in vivo area under curve and apparent distribution volume of honokiol in drug-loaded micelles were 2- and 1.69-folds higher than that for pure honokiol, with its obvious prolonged mean retention time and half-life period, respectively. The clearance rate of honokiol was also shortened about 2-fold in comparison with pure honokiol when encapsulated into the micelles. These results suggest that the developed F127-cyclodextrin micellar formulation is a promising drug delivery system for antifungal drugs.
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研究领域:
药剂学
·
生物医学
·
药物递送系统
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF MEMBRANE SCIENCE
·
2018
·
IF 6.578
Wanna Zhang,Panpan Cheng,Juan Cheng,Nan Li,Yong Wang,Jingying Yang,Xiaoyan Qiu,Hui Tan,Haizhou Yu
As researchers can control the nanostructure of the nanoporous membrane based on block copolymer precursors, it is considered to be an ideal device for separation and purification. However, the challenge still remains to make ultrathin, economic, nanopore sized and charged isoporous membranes without post-treatment. Hence, a simple, energy saving and sacrificial layer free technique was adopted to bridge the gap between the uniformly spread PS- b -PAA nanospheres and the ultrathin, negatively charged nanoporous membrane. The flux of the membrane is as high as 350 L m −2 h −1 bar −1 , while the effective pore size is only ca . 8 nm. It can separate not only the nanoparticles based on their size differences, but can also separate similarly sized proteins based on the charge differences efficiently. Moreover, nanofibers and lamellae formed nanoporous membranes have now been fabricated. The effective pore size can be customized, and can even be smaller than 1.5 nm for the lamellae formed membrane.
研究领域:
材料科学
·
生物工程
✓ 已验证
产品关联
DOI
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2015
·
IF 4.152
Man Li,Min Gao,Yunlan Fu,Chao Chen,Xuan Meng,Aiping Fan,Deling Kong,Zheng Wang,Yanjun Zhao
On-demand curcumin delivery via stimuli-responsive micellar nanocarriers holds promise for addressing its solubility and stability problem. Polymer-curcumin prodrug conjugate micelle is one of such nanosystems. The diversity of linker and conjugation chemistry enabled the generation and optimization of different curcumin micelles with tunable stimuli-responsiveness and delivery efficiency. The aim of the current work was to generate and assess acetal-linked polymeric micelles to enrich the pH-responsive curcumin delivery platforms. Curcumin was slightly modified prior to conjugating to amphiphilic methoxy poly(ethylene glycol)-poly(lactic acid) (mPEG-PLA) copolymer via an acetal bond, whereas an ester bond-linked conjugate was used as the control. The acetal-containing micelles showed a hydrodynamic diameter of 91.1 ± 2.9 (nm) and the accompanying core size of 63.5 ± 7.1 (nm) with a zeta potential of −10.9 ± 0.7 (mV). Both control and pH-labile micelles displayed similar critical micelle concentration at 1.6 μM. The acetal-containing nanocarriers exhibited a pH-dependent drug release behavior, which was faster at lower pH values. The cytotoxicity study in HepG2 cells revealed a significantly lower IC 50 at 51.7 ± 9.0 (μM) for acetal-linked micelles in contrast to the control at 103.0 ± 17.8 (μM), but the polymer residue showed no cytotoxicity upon drug release. The acetal-linked micellar nanocarrier could be a useful addition to the spectrum of currently available stimuli-responsive curcumin nano-formulations.
研究领域:
药学
·
纳米技术
·
药物递送系统
✓ 已验证
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）