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JOURNAL OF COLLOID AND INTERFACE SCIENCE · 2016 · IF 3.782

Self-assembled micelles based on Chondroitin sulfate/poly (d,l-lactideco-glycolide) block copolymers for doxorubicin delivery

Hui Zhang,Jiangkang Xu,Liang Xing,Jianbo Ji,Aihua Yu,Guangxi Zhai

Doxorubicin (DOX) is one of the most common chemotherapeutic agents for the treatment of various cancers, but its clinical usage is limited by dose-dependent cardiotoxicity. We have recently synthesized a series of Chondroitin sulfate/poly ( d , l -lactideco-glycolide) block copolymers (Chs- b -PLGA) with different length of hydrophobic block by an end-to-end coupling strategy. The structure of the amphiphilic block copolymers with low critical micelle concentration (∼28   mg/L) were confirmed by 1 H NMR. The copolymers could self-assemble into stable micelles in aqueous environment with homogeneous size distribution and negative zeta potential . The hemolytic study indicated their excellent blood compatibility and potential application for intravenous administration. DOX can be efficiently encapsulated by the Chs- b -PLGA micelles. The DOX-loaded micelles showed a sustained and pH dependent drug release behavior. The cytotoxicity assay showed no associated toxicity with blank micelles while concentration-related cell inhibition with DOX-loaded micelles. Moreover, fast cellular uptake of DOX-loaded micelles was observed by fluorescent microscope. In vivo pharmacokinetics study showed that the Chs- b -PLGA micelles could significantly prolong the blood circulation time of DOX. The maximum tolerated dose (MTD) of DOX-loaded micelles in Kunming mice was about 2-fold higher of the MTD of free DOX, indicating a high tolerance of the DOX-loaded micelles. In conclusion, the Chs- b -PLGA micelles would be a potentially useful drug delivery system for cancer therapy.

研究领域: 药剂学 · 药物递送 · 纳米医学 · 高分子科学 · 癌症治疗 · 生物医学工程
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INTERNATIONAL JOURNAL OF POLYMER ANALYSIS AND CHARACTERIZATION · 2018 · IF 1.333

Synthesis and characterization of poly(d,l-lactide-co-glycolide) modified by maleic anhydride and 1,4-butanediamine

Qiao Zhang,Jianjun Fang,Wenjuan Liu,Yunhui Zhao,Tianlong Huang,Jiale Cui,Yun Yang,Zhihua Zhou

Bone tissue engineering is sought to apply strategies for bone defects healing biodegradable porous scaffolds without limitations and shortcomings. In this work, we have developed a novel maleic anhydride (MAH) and 1,4-butanediamine modified poly(lactide-co-glycolide) polymer (BMPLGA). The synthesized polymer was characterized by Fourier transform infrared spectrometry (FTIR), Nuclear magnetic resonance spectra (1H NMR), gel permeation chromatography (GPC) and contact angle measurements. In addition, cell morphologies in the extracts and cell cytotoxity were also studied. The results showed that the BMPLGA was successfully obtained by introducing MAH and 1,4-butanediamine into PLGA in bulk. The introduction of anhydride and amino groups improved the hydrophilicity of PLGA. Fibroblastic cells showed normal morphologies in BMPLGA extracts, and the BMPLGA materials showed no cell cytotoxicity. The synthetic BMPLGA material may have potentials for biomedical applications due to improving hydrophilicity.

CAS / MDL: 301-10-0 110-60-1
研究领域: 生物材料学 · 医学工程
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RSC Advances · 2018 ·Vol. 8 ·期 48 ·27191-27200 · IF 2.936

Recombinant human BMP-7 grafted poly(lactide-co-glycolide)/hydroxyapatite scaffolds via polydopamine for enhanced calvarial repair

Qinli Xu,Ye Li,Yuhang Zhu,Kunchi Zhao,Rui Gu,Qingsan Zhu

Poly(lactic-co-glycolic acid) (PLGA) and hydroxyapatite (HA) are considered potential osteoinductive materials because of their biodegradability and mineralization features. However, the hydrophobicity of scaffold surfaces is less supportive of cell attachment and proliferation because of poor wettability. The mode of binding of growth factors to the scaffold also affects cell differentiation into osteoblasts. The half-life of a growth factor in vivo can be increased by binding the factor to the scaffold surface. In this work, we prepared a porous PLGA/HA scaffold grafted with recombinant human bone morphogenic protein-7 (rhBMP-7) attached via polydopamine (pDA) for bone repair. The pDA coated PLGA/HA (pDA-PLGA/HA) scaffolds were characterized by energy dispersive X-ray analysis and Fourier-transform infrared spectroscopy. The microstructure and porosity of PLGA/HA scaffolds were analyzed by scanning electron microscopy and micro-computed tomography. The release profile of rhBMP-7 grafted onto the pDA-PLGA/HA (pDA-PLGA/HA/BMP-7) scaffolds was examined for 21 days. The attachment efficiency, cell proliferation rate, alkaline phosphatase activity, calcium deposition, and osteoblast-related gene expression of bone marrow-derived stem cells to PLGA/HA, pDA-PLGA/HA, and pDA-PLGA/HA/BMP-7 scaffolds were evaluated. To assess the ability of bone repair in vivo, scaffolds were implanted into critical-sized calvarial defects created in mice, and the in vivo tissue-engineered bone was monitored by micro-computed tomography and histology. In vivo experiments revealed rapid healing of the defects treated with the pDA-PLGA/HA/BMP-7 scaffolds compared with pDA-PLGA/HA and PLGA/HA scaffolds at week 8 post-surgery. These results collectively demonstrate that the rhBMP-7-immobilized PLGA/HA scaffold via pDA is a promising candidate for calvarial repair.

研究领域: 生物医学工程 · 组织工程 · 材料科学 · 骨科
✓ 已验证 产品关联 DOI PubMed 高影响因子
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POLYMERS FOR ADVANCED TECHNOLOGIES · 2023 ·Vol. 34 ·期 5 ·1739-1751 · IF 3.4

3D printed peripheral vascular stents based on degradable poly(trimethylene carbonate-b-(L-lactide-ran-glycolide)) terpolymer

Na Ni,Tiantang Fan,Wuyou Ye,Qi Xia,Dongyang Liu,Jingwen Qin,Zhongyong Fan,Qing Liu

Poly( L -lactic acid) (PLLA) is a biocompatible material and has found its application in bioresorbable vascular stents (BVS). However, the crystallization of pure PLLA makes it brittle as a medical implant device. In this work, the biodegradable poly(1,3-trimethylene carbonate- b -( L -lactide- ran -glycolide acid)) (PTLG) terpolymers with improved mechanical performance were developed and processed into peripheral vascular stents by a novel 3D 4-axial printing technology. The PTLG terpolymers were successfully synthesized by ring-opening copolymerization of L -lactic acid (LLA), 1,3-trimethylene carbonate (PTMC) and glycolide acid (GA) units. The crystallinity and mechanical properties of the PTLG terpolymers with various degradation rate depends on the chain sequence structure and the component contents. Compared with the stent prepared by laser engraving, the peripheral vascular stent prepared by the 3D 4-axial printing technology exhibit a finer structure and smoother strut surface. It was found that both the strut diameters and the molecular weight of PTMC affect the radial force of the stents and that the apparent activation energy of thermal decomposition of the stents is mainly influenced by the molecular weight of PTMC and the component ratio. Therefore, the addition of the PTMC segment can effectively improve the flexibility of the PTLG terpolymer stent and the 3D printed PTLG terpolymer-based stent. Furthermore, CCK-8 and live/dead staining suggested that the stents have good biocompatibility.

CAS / MDL: 504-63-2
研究领域: 生物医学工程 · 材料科学 · 聚合物化学
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Contrast Media & Molecular Imaging · 2018 · IF 2.934

Carboxyl of Poly(D,L-lactide-co-glycolide) Nanoparticles of Perfluorooctyl Bromide for Ultrasonic Imaging of Tumor

Shengjuan Luo,Jinsong Ding,Peiqi Wang,Zheng Wang,Xiaoqian Ma,Cejun Yang,Qi Liang,Pengfei Rong,Wei Wang

Perfluorooctyl bromide (PFOB) enclosed nanoparticles (NPs) as ultrasonic contrasts have shown promising results in the recent years. However, NPs display poor contrast enhancement in vivo. In this work, we used the copolymers poly(lactide-co-glycolide) carboxylic acid (PLGA-COOH) and poly(lactide-co- glycolide) poly(ethylene glycol) carboxylic acid (PLGA-PEG-COOH) as a shell to encapsulate PFOB to prepare a nanoultrasonic contrast agent. The NPs were small and uniform ( nm with a polydispersity index of ) with a complete shell nuclear structure under the transmission electron microscopy (TEM). In vitro, when concentration of NPs was ≥10 mg/ml and clinical diagnostic frequency was ≥9 MHz, NPs produced intensive enhancement of ultrasonic gray-scale signals. NPs could produce stable and obvious gray enhancement with high mechanical index (MI) (MI > 0.6). In vivo, the NPs offered good ultrasound enhancement in tumor after more than 24 h and optical imaging also indicated that NPs were mainly located at tumor site. Subsequent analysis confirmed that large accumulation of fluorescence was observed in the frozen section of the tumor tissue. All these results caused the conclusion that NPs encapsulated PFOB has achieved tumor-selective imaging in vivo.

CAS / MDL: 423-55-2
研究领域: 医学影像学 · 生物材料学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Science of Advanced Materials · 2021 ·Vol. 13 ·期 4 ·683-693 · IF 1.474

Preparation of Absorbable Suture Biomaterial Formed by Glycolide/Lactide and Its Application in the Congenital Thumb Deformity Surgery

Zhou Yang,Lou Xupeng,Zhao Jialin,Chen Zhe,Le Fuhuan,Fang Yousheng

Conducting polymers (CPs) can regulate cell behavior and promote the regeneration of damaged tissues, which are widely applied in tissue engineering. In this study, poly(3-hexylthiophene) (PHTP) was first obtained by the catalyst + transfer poly-condensation method, and then, it was mixed with poly(lactide-co-glycolide) (PLGA) to obtain a composite material with superconductivity (PHTP/PLGA). Besides, ferric chloride (FeCl3) was selected as the dopant, and the doping time was changed, so as to obtain 5 PHTP/PLGA materials with different conductivity (10-7 S/cm, 10-6 S/cm, 10-5 S/cm, 10-4 S/cm, and 10-3 S/cm). While PHTP/PLGA was physically characterized, the cell proliferation ability and blood compatibility of this series of materials were further analyzed, and the materials were made into medical sutures for the treatment of congenital thumb deformities. In the experiment, the surface morphology, hydrophilicity, and hydrophobicity of materials with different conductivity would not affect the difference in cell behavior. Using mouse embryonic osteoblasts (MC3T3-E1) as the research objects, increasing PHTP/PLGA conductivity could promote MC3T3-E1 alkaline phosphatase activity cell mineralization, and collagen type I expression. PHTP/PLGA series materials had a low hemolysis rate and were not easily affected by platelet adhesion and activation, meaning that they would not cause coagulation. The material was applied in the direct suture method of hammer deformity, and the results showed that the patient’s deformed thumb had a knot reaction and local skin edge necrosis. After dressing change, it gradually improved. Moreover, the excellent and good rate of deformed thumb based on this material was higher than that of wire extraction method and Kirschner wire fixation method (P < 0.05).

研究领域: 生物材料 · 组织工程 · 生物医学工程 · 骨科手术
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Journal of Macromolecular Science Part B-Physics · 2019 · IF 1.204

In-Vitro Degradation Behaviors of Composite Scaffolds Based on 1,4-Butadnediamine Modified Poly(lactide-co-glycolide) and Nanobioceramics

Zhiyuan Peng,Ting Zou

In-vitro degradation behaviors of composite scaffold materials composed of 1,4-butanediamine modified poly(lactide-co-glycolide) (BMPLGA), nanobioactive glass (NBG) and β-tricalcium phosphate (β-TCP) were systematically investigated in phosphate-buffered solution (PBS) at 37 °C. The properties of the BMPLGA/NBG-β-TCP and BMPLGA scaffolds, including the changes of pH value, mass, water uptake, compressive strength and molecular mass, were investigated as a function of degradation time. The results showed that the introduction of the NBG and β-TCP particles played important roles in the degradation of BMPLGA matrix. The degradation rate of the BMPLGA/NBG-β-TCP scaffolds was slower than that of the BMPLGA scaffolds.

研究领域: 生物材料 · 组织工程 · 高分子科学 · 生物陶瓷 · 降解行为
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Journal of Macromolecular Science Part B-Physics · 2020 · IF 0.911

Preparation and Characterization of Poly(L-lactide-co-glycolide-co-ε-caprolactone) Scaffolds by Thermally Induced Phase Separation

Ping Chen,Zhihua Zhou,Wenjuan Liu,Yanmin Zhao,Tianlong Huang,Xiaofei Li,Jianglong Duan,Jianjun Fang

The technique of thermally induced phase separation (TIPS) is favorable for the fabrication of a porous scaffold due to a number of advantages. In this work the poly(L-lactide-co-glycolide-co-ε-caprolactone) (PLLGC) terpolymer was synthesized by melt copolymerization and porous scaffolds thereof from its solution in 1,4-dioxane were fabricated by using the TIPS method. The effects of fabrication parameters, including polymer concentration and freezing temperature, on the morphology, pore size and mechanical properties were studied. The results showed that the average pore size of the PLLGC porous scaffold increased with a decrease in PLLGC concentration and the pore size resulting from freezing at 4 °C (about 20–100 μm) was significantly larger than for other samples (20–50 μm) frozen at lower temperatures. The porosity of the scaffolds decreased with increasing PLLGC concentration or decreasing freezing temperature. On the other hand, the compressive strength of the scaffolds increased with the increase of PLLGC concentration or the decrease of freezing temperature, as would be expected. The present results can be applied in design to control the processing parameters of TIPS for a scaffold with desired pore morphology.

研究领域: 生物材料 · 组织工程 · 高分子科学 · 材料表征
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INTERNATIONAL JOURNAL OF POLYMER ANALYSIS AND CHARACTERIZATION · 2017 · IF 0

Synthesis, characterization, and degradation behaviors of poly(D,L-lactide-co-glycolide) modified by maleic anhydride and ethanediamine

Jiale Cui,Zhihua Zhou,Yun Yang,Wenjuan Liu,Yunfei Zhao,Cheng Peng,Tianlong Huang,Hu Zhou,Lihua Liu,Qiao Zhang

In order to improve hydrophilicity and settle the acidity in hydrolysis, a novel ethanediamine (EDA) and maleic anhydride (MAH) modified poly(D,L-lactide-co-glycolide) (PLGA) polymer (EMPLGA) was synthesized. Fourier Transform Infrared Spectrometer (FTIR), Gel Permeation Chromatography (GPC), Nuclear Magnetic Resonance (1HNMR), titration and the water contact angles were employed to characterize the synthesized polymer. The effects of various polymerization conditions on weight average molecular mass (Mw), polydispersity index (PDI) and anhydride content of MPLGA were investigated. The degradation behaviors of PLGA, MPLA and EMPLGA were also studied by observation of the changes of the pH value of incubation medium, molecular weight and weight loss ratio for a time interval of 25 days in-vitro, respectively. The results showed that MPLGA with high anhydride content was successfully obtained by directly ring-opening polymerization and ethanediamine was further grafted onto MPLGA, and there is almost unchanged in Mw between MPLGA and EMPLGA polymers. The introduction of anhydride and amino groups improved the hydrophilicity of PLGA. A uniform degradation of EMPLGA was observed in comparison with an acidity-induced auto-accelerating degradation featured by PLGA and MPLGA. The results revealed that the introduction of ethanediamine into PLGA has weakened or neutralized the acidity of PLGA degradation products.

CAS / MDL: 301-10-0
研究领域: 材料科学 · 生物医学工程
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PHARMACOLOGICAL RESEARCH · 2020 · IF 5.893

Light-triggered OVA release based on CuS@poly(lactide-co-glycolide acid) nanoparticles for synergistic photothermal-immunotherapy of tumor

Zhenzhen Chen,Qian Zhang,Lingjun Zeng,Jialiang Zhang,Zhihong Liu,Minxin Zhang,Xueting Zhang,Hang Xu,Hongtao Song,Chun Tao

The immunotherapy played a vital role in the treatment of metastatic tumor. To further enhance the effect of the immunotherapy, the combination of photothermal effect can not only eradicate the tumor cells by hyperthermia, but also improved the antigen release in vivo to achieve enhanced immune responses. In this study, a core-shell structured nanocomplex was developed by loading of ovalbumin (OVA) and copper sulfide nanoparticles (CuS-NPs) into the poly(lactide-co-glycolide acid) nanoparticles (PLGA-NPs). The CuS-NPs exhibited favorable photothermal effect, which significantly kill the 4T1 tumor cells in vitro . The photothermal effect of the CuS-NPs accelerated the OVA release, which led to higher levels of IL-6, IL-12 and TNF-α, and activation of CD8 + T cells. Both of the OVA-PLGA-NPs and CuS-NPs with NIR light irradiation contributed inhibited primary tumor while the growth of the distant tumors was not hindered. The irradiated [email protected] exhibited a minimal primary tumor because of the combined effect of photothermal therapy and immunotherapy. Moreover, the irradiated [email protected] showed the most extensive distribution of CD8 + T cells in the primary and distant tumor, which blocked the rise of the distant tumor. In conclusion, the [email protected] presented as a promising strategy for metastatic tumor therapy.

✓ 已验证 产品关联 DOI PubMed 高影响因子
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POLYMERS FOR ADVANCED TECHNOLOGIES · 2018 ·Vol. 30 ·期 1 ·40-50 · IF 2.137

Drug release and biocompatibility of self-assembled micelles prepared from poly (ɛ-caprolactone/glycolide)-poly (ethylene glycol) block copolymers

Feng Su,Xiangke Sun,Rongye Li,Yuandou Wang,Laishun Xi,Yangsheng Chen,Suming Li

A series of poly(ɛ-caprolactone/glycolide)-poly(ethylene glycol) (P(CL/GA)-PEG) diblock copolymers were prepared by ring opening polymerization of a mixture of ɛ-caprolactone and glycolide using mPEG as macro-initiator and stannous octoate as catalyst. Self-assembled micelles were prepared from the copolymers using nanoprecipitation method. The micelles were spherical in shape. The micelle size was larger for copolymers with longer PEG blocks. In contrast, the critical micelle concentration of copolymers increased with decreasing the overall hydrophobic block length. Drug loading and drug release studies were performed under in vitro conditions, using paclitaxel as a hydrophobic model drug. Higher drug loading was obtained for micelles with longer poly(ε-caprolactone) blocks. Faster drug release was obtained for micelles of mPEG2000 initiated copolymers than those of mPEG5000 initiated ones. Higher GA content in the copolymers led to faster drug release. Moreover, drug release rate was enhanced in the presence of lipase from Pseudomonas sp., indicating that drug release is facilitated by copolymer degradation. The biocompatibility of copolymers was evaluated from hemolysis, dynamic clotting time, and plasma recalcification time tests, as well as MTT assay and agar diffusion test. Data showed that copolymer micelles present outstanding hemocompatibility and cytocompatibility, thus suggesting that P(CL/GA)-PEG micelles are promising for prolonged release of hydrophobic drugs.

CAS / MDL: 33069-62-4 301-10-0
研究领域: 材料科学 · 药学 · 生物医学工程
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POLYMERS & POLYMER COMPOSITES · 2015 · IF 0.271

Synthesis and Characterization of Star-Shaped Poly(Lactide-Co-Glycolide) Using Poss as An Initiator, and Its Drug-Loaded Microspheres

Xiaojing Zhang,Chong Li,Yuelei Hu,Jiashu Sun,Shaoming Fang

In this paper, a series of star-shaped poly(lactide-co-glycolide)s (sPLGA) with different block ratios were prepared by the ring-opening copolymerization of D,L-lactide (LA) and glycolide (GA) with multi-hydroxyl polyhedral oligomeric silsesquioxane core as an initiator and tin (II) 2-ethylhexanoate (Sn(Oct)2) as the catalyst. The products were characterized by NMR, FT-IR, GPC, XRD, DSC, TGA and viscosity measurements. The results show that the contents of PLA and PGA segments in sPLGA can be controlled by the feed ratios of the copolymerization. The glass transition temperature and crystallinity of sPLGA decrease and the crystalline sPLGA becomes amorphous with increasing the molar feed ratio between GA and LA from 10:90 to 50:50. The drug-loaded sPLGA microspheres were prepared by an emulsion solvent evaporation method. The morphology and the drug release property were investigated by SEM, dynamic light scattering (DLS) and ultraviolet spectrophotometry (UV). The results indicate that the sPLGA80 microsphere surface was smooth and the mean diameter was about 1.27μm. The sPLGA80 microspheres showed good drug loading and release properties.

研究领域: 材料科学 · 药剂学
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