EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
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2012
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IF 3.212
Fatima Zohra Dahmani,Hui Yang,Jianping Zhou,Jing Yao,Ting Zhang,Qiang Zhang
In order to enhance paclitaxel oral bioavailability, mixed polymeric micelles that comprised of pluronic copolymers and low molecular weight heparin-all-trans-retinoid acid (LHR) conjugate were developed. PTX-loaded mixed polymeric micelles (MPMs) were prepared by dialysis method with high drug loading 26.92 ± 2.08% and 25.82 ± 1.9% for F127/LHR and P188/LHR MPMs respectively, and were found to be spherical in shape with an average size of around 140 nm and a narrow size distribution. In vitro release study showed that pluronic/LHR MPMs exhibited delayed release characteristics compared to Taxol and faster drug release profile compared to LHR plain polymeric micelles (PPMs). The cytotoxic activity of PTX-loaded pluronic/LHR MPMs was slightly higher than LHR PPMs in MCF-7 cells ( p < 0.01). In situ effective permeability of PTX through rat small intestine was 5- to 6-fold higher with mixed micelles than that of Taxol. Moreover, pluronic/LHR MPMs achieved significantly higher AUC and C max level than both of LHR PPMs and Taxol. This enhancement might be due to the inhibition of both P-glycoprotein efflux system and cytochrome P450 metabolism by pluronic copolymers. The current results encourage further development of paclitaxel mixed polymeric micelles as an oral drug delivery system .
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JOURNAL OF POLYMER SCIENCE
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2025
·
IF 3.6
Sunqi Yu,Siyuan Chen,Tianrui Tong,Yunfeng Yan,Qi Shuai
Micelle-based drug delivery systems (DDS) have emerged as a promising solution to address challenges associated with the in vivo delivery of hydrophobic anticancer chemotherapeutics. However, micelles still encounter issues such as drug pre-leakage and poor stability in physiological conditions. To overcome these limitations, we developed a core-cross-linking strategy utilizing amphiphilic copolymers, mPEG- b- P(AVL- co -LA) (mPPAL), functionalized with phenylboronic acid (PBA), and catechol by CuAAc “click” chemistry, respectively. These copolymers self-assembled into core-cross-linked micelles (CLMs), featuring boronic ester bonds, which were characterized through a series of evaluations. The CLMs exhibited a rational particle size, uniform morphology, low critical micelle concentration (CMC), high PTX loading capacity, and excellent stability. Two promising micelles, CLM1 and CLM3, were identified, and their responsiveness to acidic pH and elevated levels of ROS was confirmed to enable controlled PTX release. The results of MTT assay and hemolytic analysis demonstrated high biocompatibility and potential in vivo application of these selected CLMs. The anticancer efficacy of the selected PTX-CLMs was further validated through MTT assay and 3D tumor spheroid studies. Fluorescence microscopy and flow cytometry demonstrated rapid intracellular uptake of the CLMs. In vivo biodistribution studies demonstrated successful accumulation in the targeted tumor tissue. These findings suggest that the boronic ester-based CLMs developed in this study are a promising nanocarrier for effective PTX delivery. Graphical Phenylboronic acid (PBA) and catechol-modified amphiphilic copolymers (mPPAL@R) were synthesized via ring-opening polymerization followed by CuAAc click chemistry. These copolymers were employed to construct pH- and ROS-dual-responsive micelles with boronic ester core-crosslinking. A series of in vitro and in vivo experiments were conducted to evaluate PTX-loaded micelles, demonstrating their significant potential for effective PTX delivery.
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JOURNAL OF MOLECULAR LIQUIDS
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2024
·
IF 5.3
Wenjing Zhang,Shengfeng Ye,Zhaolan Zhai,Dan Wang,Shibin Shang,Zhanqian Song
Fluorescent nanomaterials have drawn considerable attentions due to their high fluorescence sensitivity, excellent signal stability and tunable luminescent properties. A bio-based aggregation-induced emission (AIE) surfactant (Sodium 4-(tetraphenylstyrene)maleate, MPA-TPE-Na) was prepared from rosin, which showed typical AIE characteristic, obvious solvatochromism and a large Stokes shift (>100 nm). AIE viscoelastic solutions were further prepared by complexing MPA-TPE-Na and cetyltrimethylammonium bromide (CTAB) through coordinating aggregation and their microstructure, fluorescence properties and viscoelasticities were investigated. The aggregates in the viscoelastic solutions were wormlike micelles. As the concentration of MPA-TPE-Na increased, the fluorescence intensity of the viscoelastic solutions increased, and their viscosity increased at first and then decreased. The fluorescence emission intensity of the viscoelastic solutions was barely affected by the change in pH. But reducing the pH could increase its viscosity. This system can specifically recognize Fe 3+ without any organic solvent and has anti-interference ability. The present work provided a bio-based fluorescent nanomaterial and verified the feasibility of preparing aqueous AIE nanomaterials by modifying AIE groups with rosin skeleton.
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Acta Biomaterialia
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2016
·
IF 6.008
Jiulong Zhang,Xiufeng Zhao,Qing Chen,Xiaoyi Yin,Xiu Xin,Kexin Li,Mingxi Qiao,Haiyang Hu,Dawei Chen,Xiuli Zhao
Multidrug resistance (MDR) of tumor cells is becoming the main reason for the failure of chemotherapy and P-glycoprotein (P-gp) mediated drug efflux has demonstrated to be the key factor for MDR. To address this issue, a novel pH-responsive mixed micelles drug delivery system composed of dextran-g-poly(lactide-co-glycolide)-g-histidine (HDP) and folate acid-D-α-tocopheryl polyethylene glycol 2000 (FA-TPGS2K) copolymers has been designed for the delivery of antitumor agent, paclitaxel (PTX) via FA-receptor mediated cell endocytosis , into PTX-resistant breast cancer MCF-7 cells (MCF-7/PTX). PTX-loaded FA-TPGS2K/HDP mixed micelles were characterized to have a small size distribution, high loading content and excellent pH-responsive drug release profiles. Compared with HDP micelles, FA-TPGS2K/HDP mixed micelles showed a higher cytotoxicity against MCF-7 and MCF-7/PTX cells due to the synergistic effect of FA-receptor mediated cell endocytosis, pH-responsive drug release and TPGS mediated P-gp inhibition. P-gp expression level, ATP content and mitochondrial membrane potential change have been measured, the results indicated blank FA-TPGS2K/HDP mixed micelles could inhibit the P-gp activity by reducing the mitochondrial membrane potential and depleting ATP content but not down-regulating the P-gp expression. In vivo antitumor activities demonstrated FA-TPGS2K/HDP mixed micelles could reach higher antitumor activity compared with HDP micelles for MCF-7/PTX tumor cells. Histological assay also indicated that FA-TPGS2K/HDP mixed micelles showed strongly apoptosis inducing effect, anti-proliferation effect and anti-angiogenesis effect. All these evidences demonstrated this pH-sensitive FA-TPGS2K/HDP micelle-based drug delivery system is a promising approach for overcoming MDR. Statement of Significance In this work, a novel FA-TPGS2K copolymer has been synthesized and used it to construct mixed micelles with HDP copolymer to overcome MDR effect. Furthermore, a series in vitro and in vivo evaluations have been made, which supported enough evidences for the efficient delivery of antitumor drug to MDR cells.
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DRUG DELIVERY
·
2023
·
IF 6
Ru Wang,Nuannuan Li,Tianyu Zhang,Yiying Sun,Xiaoyan He,Xiaoyan Lu,Liuxiang Chu,Kaoxiang Sun
Mitoxantrone (MX) can induce the immunogenic-cell death (ICD) of tumor cells and activate anti-tumor immune responses. However, it can also cause high expression of indole amine 2, 3-dioxygenase (IDO) during ICD, leading to T-cell apoptosis and a weakened immune response. An IDO inhibitor, 1-methyl tryptophan (1-MT), can inhibit the activity of IDO caused by MX, resulting in enhanced chemo-immunotherapy. Here, MX-1-MT was connected by ester bond which could be broken in an acidic tumor microenvironment. MX-1-MT was combined with polyethylene glycol (PEG) via a disulfide bond which could be reduced by glutathione overexpressed in tumors, thereby accelerating drug release at target sites. Folic acid-modified distearoyl phosphoethanolamine-polyethylene glycol (DSPE-PEG-FA) was introduced to form targeting micelles. The micelles were of uniform particle size, high stability, and high responsiveness. They could be taken-up by drug-resistant MCF-7/ADR cells, displayed high targeting ability, and induced enhanced cytotoxicity and ICD. Due to 1-MT addition, micelles could inhibit IDO. In vivo studies demonstrated that micelles could accumulate in the tumor tissues of nude mice, resulting in an enhanced antitumor effect and few side-effects.
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Materials Today Nano
·
2021
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IF 8.109
T. Zhou,H. Xiong,S.Q. Wang,H.L. Zhang,W.W. Zheng,Z.R. Gou,C.Y. Fan,C.Y. Gao
Selective exhaustion of over-expressed reactive oxygen species (ROS) is of great significance in the therapy of osteoarthritis (OA) because of the inhibiting effect on oxidative stress and inflammation. Herein, a ROS-scavenging and drug-release platform was prepared via encapsulating dexamethasone acetate (DA)-loaded ROS erasable poly(ethylene glycol)- b -polythioketal- b -poly(ethylene glycol) (PEG-PTK-PEG) micelles (PDM) into an injectable hydrogel. The hydrogel ( [email protected] ) was constructed by Schiff base reaction between hydrazide-grafted hyaluronic acid (HA-ADH) and aldehyde-modified dextran (Dex-ALH), achieving a self-healing property for viscosupplementation. The PDM imparted enhanced antioxidant capability to the hydrogel, which, in turn, endowed the PDM with prolonged retention and sustained DA release. The intraarticularly administered multifunctional injectable hydrogel potently diminished inflammation via depleting ROS and suppressing inflammatory cytokines, as well as downregulating pro-inflammatory M1 macrophages ratio in a rat OA model. The developed therapeutic system significantly alleviated OA symptoms, embodying the excellent capability of preventing cartilage extracellular matrix degeneration with negligible toxicity in vivo .
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MACROMOLECULAR CHEMISTRY AND PHYSICS
·
2021
·Vol. 222
·期 13
·2000365
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IF 2.527
Qiong Guo,Jiangtao Liu,Hong Yang,Zhongli Lei
Stimuli-responsive chemical bonds have already been widely applied to construct nanomaterials, however, such materials rarely have great amounts of responsive groups and stable structures. Herein, a triple-stimuli-responsive interface-cross-linked (ICL) copolymer which is synthesized via Cu(I)-catalyzed azide-alkyne cycloaddition click polymerization and atom transfer radical polymerization (ATRP), is reported. N, N′-bis(bromoacetyl) cystamine is used for intramolecular crosslinking of the linear polymer chains. The ο-nitrobenzyl groups, peroxalate ester bonds, disulfide bonds, and triazole units are regularly and repeatedly arranged in the hydrophobic blocks, therefore enabling the polymer a large amount of responsive chemical bonds. The polymer self-assembles into spherical micelles with uniform size in deionized water. Using hydrophobic dye Nile red (NR) as a model drug to evaluate the effect of release in vitro, the multi-stimuli-sensitive release properties of the ICL micelles are investigated in detail by means of UV–vis, transmission electron microscopy, dynamic light scattering, and fluorescence spectrophotometry, and the results indicate the ICL micelles can respond to the photo, oxidation, or reduction responsiveness either independently or synergistically. Furthermore, the cross-linked structure enhances the stability of the micelles and rarely impacts the total amount of drug release. The research may have applications in the field of drug delivery systems for cancer therapy.
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Polymer Chemistry
·
2017
·Vol. 8
·期 43
·6675-6687
·
IF 5.375
Da Huang,Yaqiang Wang,Fei Yang,Hong Shen,Zuquan Weng,Decheng Wu
Recently, nanoparticles self-assembled from amphiphilic supramolecular linear-dendritic block copolymers (LDBCs) have attracted great interest, since the combination of linear and dendritic polymers can incorporate the unique properties of the different segments but avoid some inherent drawbacks of dendrimers, not to mention that the components can be flexibly adjusted to enrich their functionality. In this study, LDBCs formed by host–guest recognition of polyacetal dendrimers with a β-cyclodextrin core and adamantane-terminated zwitterionic poly(sulfobetaine) could self-assemble into micelles and vesicles by varying the hydrophilic/hydrophobic ratio. Owing to the acid-labile characteristic of the dendritic segments, the micelles and vesicles were degradable and could release their payloads in a pH-responsive manner. The incorporation of zwitterionic linear segments gave the micelles and vesicles a charge-reversal ability and excellent resistivity to protein absorption, leading to higher affinity to cell membranes than conventional PEG-coated nanoparticles. In addition, the potential of these nanoparticles as anticancer drug carriers was preliminarily evaluated by using doxorubicin as a model drug and the results indicated that the DOX-loaded micelles and vesicles exhibited remarkable anticancer activity. This study cast a new light on the application of dendrimers and these micelles and vesicles constructed from LDBCs may be promising candidates as anticancer drug delivery platforms for cancer therapy.
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MACROMOLECULAR RAPID COMMUNICATIONS
·
2015
·Vol. 36
·期 15
·1402-1408
·
IF 4.941
Rui Qi,Yong Jin,Xinfeng Cheng,Baozhu Fan,Tongbing Sun,Shaojun Peng,Hanping Li
A novel rod-containing block copolymer is constructed by supramacromolecular self-assembly of α-cyclodextrin and a triblock copolymer with methoxy polyethylene glycol as the flanking chains and the midterm block alternately connected by 2,2-dimethylolbutyric acid and isophorone diisocyanate. The assembled rod-containing block copolymer shows an exciting phenomenon of concentration- and pH-dependent morphological switching of well-defined nanostructures. In the solutions at pH 9.2, spherical micelles, rod-like micelles, and hydrogel are observed successively with an increase of the concentration. Notably, the rod-like micelles are composed of spherical segments due to the combination of the crystalline cores of the spherical micelles. In addition, 1D nanostructures with different curvatures from linear rod-like micelles (pH 9.2) to ring-shaped micelles (pH 7.5) can be obtained by controlling the pH values of the assembled systems.
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LANGMUIR
·
2014
·
IF 4.384
Yan Liu,Min Tian,Huan Chang,Jinqiang Jiang,Xiangyang Yan,Zhaotie Liu,Zhongwen Liu
It is possible that the hydrophobic guest within amphiphilic polymer micelles may leak out and be captured by other species before polymer micelles adhere to the desired focus because of the complexity in an actual release procedure, rendering the reduced efficiency of the nanocarrier system. To describe such a scenario, two water-soluble fluorescent amphiphilic random copolymers of PAV and PAA with photo-cross-linkable coumarin and anthracene pendants, respectively, were chosen to investigate the equilibrating immigration and maleimide-anthracene-based Diels–Alder-trapping of hydrophobic octylmaleimide guest from one type of photo-cross-linked polymer micelles of PAV85% to another of PAA66% in aqueous solution using the emission and absorption spectra techniques.
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CARBOHYDRATE POLYMERS
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2018
·
IF 5.158
Shuang Bai,Meili Hou,Xiaoxiao Shi,Jiucun Chen,Xiaoqian Ma,Yong-E Gao,Yajun Wang,Peng Xue,Yuejun Kang,Zhigang Xu
As one of the medical polymers approved by US Food and Drug Administration (FDA), poly(ethylene glycol) has low toxicity, high stability, good biocompatibility, unique physical and chemical properties. Cyclodextrin is an ideal candidate as a drug carrier due to its special structures and characteristics. These two materials were successfully assembled through chemosynthesis in combination with the hydrophilic poly(ethylene glycol) methyl ether methacrylate (OEGMA) chain and hydrophobic polymeric camptothecin (CPT) chain by atom transfer radical polymerization (ATRP). The introduction of disulfide bond of monomer was aimed to realize reduction agent-triggered release of active CPT. The obtained amphipathic prodrug [(Denoted as PC-PCPT- b -POEGMA (PCCO)] could form nano-sized polymeric micelles, which could release more than 85% of the loaded CPT via triggered cleavage of the disulfide linker. The cellular co-localization study revealed the potential pathway of drug internalization. Moreover, the PCCO micelles showed good biocompatibility in vivo after intravenous injection on a mouse model. This new CPT-loaded prodrug system could be prepared with low cost, and showed efficient and controlled drug release and favorable biocompatibility, demonstrating a promising potential as a stimuli-responsive polymeric prodrug for future clinical applications.
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BIOMATERIALS
·
2016
·
IF 8.387
WenTing Li,JinRong Peng,LiWei Tan,Jing Wu,Kun Shi,Ying Qu,XiaWei Wei,ZhiYong Qian
Patients suffering from cancer have benefited from combination therapy. Nanocarriers are the ideal candidates for combination therapy. In this study, we constructed docetaxel (DTX) loaded micellar nanomedicines co-loaded with near infrared (NIR) dye-IR820 for photothermal therapy (PTT)/photodynamic therapy (PDT)/chemotherapy of breast cancer. Lyp-1, a tumor homing peptide, was introduced into the nanosystems to construct the active targeting nanomedicine. In order to deliver IR820 to the tumor site and overcome its short lifetime in vivo , a PEI derivative—PCL-g-PEI was introduced. IR820 with negative charge was formed stable static interaction with the amine groups, meanwhile, the absorption of IR820 in the NIR region was weakened. It indicated that the nanosystem constructed in this study may provide an alternative candidate for mild PTT. By the evaluation of the photothermal conversion in vivo , we can confirm that IR820 has been successfully delivered and effectively accumulated in the tumor site. Furthermore, the tumor cells targeting and anticancer performances of this nanosystem have been studied in vitro and in vivo . The results demonstrated Lyp-1 modification has enhanced the tumor targeting delivery of DTX and IR820. By combining PTT and PDT, DTX nanomedicine efficiently inhibited the growth and metastasis of breast cancer in mice. This nanosystem is a promising candidate for combination therapy of breast cancer.
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