JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2022
·
IF 5.062
Guang Ma,Xiaolin Xu,Ming Qi,Yingjian Zhang,Xiaoping Xu
Interventional therapy is very important in current clinical applications. However, the lack of quantifiable embolic agents to affect the therapeutic effects negatively. In the present study, we sought to prepare a novel embolic agent, 99m Tc-Konjac glucoman/Poly(lactide- co -glycolide)@Polyethyleneimine@Diethylenetriaminepentaacetic acid(KGM/PLGA@PEI@DTPA)microspheres, which can be located and quantified noninvasively to further evaluate its biological effects in animal models. The KGM/PLGA microspheres were prepared with water/oil/water double emulsion-solvent evaporation. Subsequently, the surface modification was performed with PEI and DTPA as a bifunctional chelator to label the microspheres with 99m Tc. The in vitro stability of 99m Tc-KGM/PLGA@PEI@DTPA was determined through instant thin layer chromatography, and the in vitro cytotoxicity of KGM/PLGA@PEI@DTPA was evaluated with CCK-8 assays. The location and quantitative calculation of 99m Tc-KGM/PLGA@PEI@DTPA in vivo were evaluated in rabbits through SPECT/CT, and the in vivo toxicity was assayed in rabbits.The microspheres showed no toxicity in vitro and in vivo , andthe diameter of microsphere was about 82.5 ± 14.5 μm(range 60–120 μm). The 99m Tc-KGM/PLGA@PEI@DTPA was stable in phosphate-buffered saline and 50% fetal bovine serum within 6 h. The Single-photon emission computed tomography/computed tomography(SPECT/CT) imaging and biodistribution results showed that microspheres were mainly distributed in the liver, kidney, and bladder, and excreted through the urinary system. And the dose of microspheres embolizing in the liver was approximately 2.54 mg, 50.79% of the total injection, an estimate calculated according to the gamma ray emission from 99m Tc in SPECT/CT.Hence, the 99m Tc-KGM/PLGA@PEI@DTPA may be as a quantitative embolic agent and provide potential clinical value for interventional therapy.
研究领域:
医学影像学
·
药剂学
✓ 已验证
产品关联
DOI
高影响因子
MACROMOLECULAR RAPID COMMUNICATIONS
·
2013
·Vol. 35
·期 5
·579-584
·
IF 4.929
Xiuli Chen,Lin Huang,Hao-Jan Sun,Stephen Z. D. Cheng,Mingqiang Zhu,Guang Yang
Liver cancer remains a significant medical problem and one promising therapeutic approach is to embolize the tumor. One emerging embolization strategy is to use thermoresponsive materials that can be injected but gel at the tumor site. It is now reported on thermoresponsive nanocomposites generated by grafting poly( N -isopropylacrylamide) chains on bacterial cellulose nanowhiskers. Chemical and physical evidences are provided for grafting and demonstrated a sol–gel transition when the temperature is increased above 34.3 °C. Cytotoxicity test in human umbilical vein endothelial cells indicates the excellent biocompatibility of these nanocomposites for use as embolic materials. These results suggest that the nanocomposites offer appropriate properties for embolization of hepatocellular carcinoma.
研究领域:
医学
·
材料科学
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF MATERIALS SCIENCE
·
2022
·Vol. 57
·期 45
·21009-21019
·
IF 4.682
Lin Lingyin,Zhou Yanfang,Chen Piaoyi,Xiao Qinglin,Ye Guodong
Transcatheter arterial embolization is an established treatment for hepatocellular carcinoma (HCC). However, the existing embolic materials still have some shortcomings, e.g., particle clumping can cause catheter occlusion. In this study, after the synthesis of monomer glyceryl triallyl ether monomer (GE), amorphous embolic agent (PGE) was synthesized by photopolymerization in the presence of GE and photoinitiator. Combined with RT-IR, TG and GPC, we verified that the polymerization followed a photo-driven radical-mediated [3 + 2] cyclopolymerization mechanism (PRMC) through experimental and modeled NMR. The macromolecular properties such as polymerization profile and morphology were studied by TG and SEM–EDS. Finally, the degradation, swelling and migration behavior of PGE were characterized, which indicated that PGE could embolize HCC by blocking the blood supply. In this study, PRMC prevented GE polymerization from degradative chain transfer with 70% yield in an hour, and 200–350 µm PGE was synthesized using this mechanism suitable for clinical use. Graphical abstract
研究领域:
医学
·
材料科学
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肿瘤学
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Yue Yu,Yang Liu,Chao Wang,Chang Chen,Qingsong Ye,Zhewei Zhang,Lifeng Luo,Chengjun Song,Chenxuan Zhao,Zhiwen Zou,Yitao Ding,Jinhui Wu
Tumor embolization therapy often involves complex procedures and poses challenges for physicians, especially with radiological imaging guidance. Inspired by physiological processes of misfolded protein aggregation and thrombus formation, we developed a protein-based embolic agent using ethiodized oil and human serum albumin for targeted tumor embolization. By occupying the hydrophobic cavity of albumin and disrupting its refolding process, these ethiodized oil bound human serum albumin nanoparticles (Oil@HSA NPs) achieve spontaneous aggregation and size growth at high concentrations, a unique advantage over conventional phospholipid nanoparticles. When combined with bacterium-induced coagulation in tumor vessels, Oil@HSA NPs selectively accumulate at tumor sites, blocking blood flow and significantly inhibiting tumor growth. This study introduces a practical and innovative approach to tumor embolization, offering a streamlined and effective alternative for vascular targeting in cancer therapy.
研究领域:
医学
·
肿瘤学
·
生物材料学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHARMACEUTICAL DEVELOPMENT AND TECHNOLOGY
·
2020
·
IF 2.169
Xiaolin Fang,Aizong Shen
Transcatheter arterial chemoembolization (TACE) is the preferred treatment for patients with advanced hepatocellular carcinoma (HCC), but it lacks safe and effective embolic agents. 5-Fluorouracil (5-FU) is a broad-spectrum anticancer drug, but its clinical application is limited due to drug resistance and toxic side effects. Therefore, in this study, we developed a new liquid embolic agent with 5-FU as the model drug. We found that this liquid embolic agent possesses good gelling properties and embolic effects. An in vitro drug release model of the agent conformed to the Weibull model. Cumulative release of the drug over 7 d was ∼90%, consisting of an initial burst followed by sustained release. Cytotoxicity testing showed that each liquid embolic composition is cytocompatible and only mildly cytotoxic. Pharmacokinetic experiments showed that the formulation significantly prolongs the t1/2 of 5-FU (approximately five times that of 5-FU solution) and 5-FU residence time in the body (approximately three times that of 5-FU solution). These results indicate that the liquid embolic agent has embolic capacity and could be used as a potential therapeutic method for TACE.
研究领域:
医学
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMACROMOLECULES
·
2024
·
IF 5.5
Shili Ai,Qinzong Gao,Gele Cheng,Pengfei Zhong,Peiyu Cheng,Yingying Ren,Hao Wang,Xu Zhu,Shanyue Guan,Xiaozhong Qu
Conventional embolists disreputably tend to recanalization arising from the low filling ratio due to their rigidity or instability. As a result, intelligent hydrogels with a tunable modulus may meaningfully improve the therapeutic efficacy. Herein, an injectable composite double-network (CDN) hydrogel with high shear responsibility was prepared as a liquid embolic agent by cross-linking poly(vinyl alcohol) (PVA) and carboxymethyl chitosan (CMC) via dynamic covalent bonding of borate ester and benzoic-imine. A two-dimensional nanosheet, i.e., layered double hydroxide (LDH), was incorporated into the network through physical interactions which led to serious reduction of yield stress for the injection of the hydrogel and the capacity for loading therapeutic agents like indocyanine green (ICG) and doxorubicin (DOX) for the functions of photothermal therapy (PTT) and chemotherapy. The CDN hydrogel could thus be transported through a thin catheter and further in situ strengthened under physiological conditions, like in blood, by secondarily cross-linking with phosphate ions for longer degradation duration and better mechanical property. These characteristics met the requirements of arterial interventional embolization, which was demonstrated by renal embolism operation on rabbits, and meanwhile favored the inhibition of subcutaneous tumor growth on an animal model. Therefore, this work makes a breakthrough in the case of largely reducing the embolism risks, thus affording a novel generation for interventional embolization.
研究领域:
生物医学工程
·
材料科学
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2014
·
IF 3.785
Ling-Ran Du,Xiao-Jing Lu,Hai-Tao Guan,Yong-Jie Yang,Meng-Jie Gu,Zhuo-Zhao Zheng,Tian-Shi Lv,Zi-Guang Yan,Li Song,Ying-Hua Zou,Nai-Qi Fu,Xian-Rong Qi,Tian-Yuan Fan
New type of liquid embolic agents based on a liquid crystalline material of glyceryl monooleate (GMO) was developed and evaluated in this study. Ternary phase diagram of GMO , water and ethanol was constructed and three isotropic liquids (ILs, GMO:ethanol:water = 49:21:30, 60:20:20 and 72:18:10 (w/w/w)) were selected as potential liquid embolic agents, which could spontaneously form viscous gel cast when contacting with water or physiological fluid. The ILs exhibited excellent microcatheter deliverability due to low viscosity, and were proved to successfully block the saline flow when performed in a device to simulate embolization in vitro . The ILs also showed good cytocompatibility on L929 mouse fibroblast cell line. The embolization of ILs to rabbit kidneys was performed successfully under monitoring of digital subtraction angiography (DSA), and embolic degree was affected by the initial formulation composition and used volume. At 5th week after embolization, DSA and computed tomography (CT) confirmed the renal arteries embolized with IL did not recanalize in follow-up period, and an obvious atrophy of the embolized kidney was observed. Therefore, the GMO-based liquid embolic agents showed feasible and effective to embolize, and potential use in clinical interventional embolization therapy.
研究领域:
生物材料学
·
介入放射学
·
药剂学
·
血管内治疗
·
转化医学
✓ 已验证
DOI
高影响因子
ACS Nano
·
2024
·
IF 15.8
Yutao Ma,Zhihua Li,Yucheng Luo,Yao Chen,Le Ma,Xiaoya Liu,Jingyu Xiao,Man Huang,Yingnan Li,Hongliang Jiang,Meijuan Wang,Xiaoqian Wang,Jiangtao Li,Jian Kong,Peng Shi,Hanry Yu,Xingyu Jiang,Qiongyu Guo
Transarterial chemoembolization (TACE), the mainstay treatment of unresectable primary liver cancer that primarily employs nondegradable drug-loaded embolic agents to achieve synergistic vascular embolization and locoregional chemotherapy effects, suffers from an inferior drug burst behavior lacking long-term drug release controllability that severely limits the TACE efficacy. Here we developed gelatin-based drug-eluting microembolics grafted with nanosized poly(acrylic acid) serving as a biodegradable ion-exchange platform that leverages a counterion condensation effect to achieve high-efficiency electrostatic drug loading with electropositive drugs such as doxorubicin (i.e., drug loading capacity >34 mg/mL, encapsulation efficiency >98%, and loading time <10 min) and an enzymatic surface-erosion degradation pattern (∼2 months) to offer sustained locoregional pharmacokinetics with long-lasting deep-tumor retention capability for TACE treatment. The microembolics demonstrated facile microcatheter deliverability in a healthy porcine liver embolization model, superior tumor-killing capacity in a rabbit VX2 liver cancer embolization model, and stabilized extravascular drug penetration depth (>3 mm for 3 months) in a rabbit ear embolization model. Importantly, the microembolics finally exhibited vessel remodeling-induced permanent embolization with minimal inflammation responses after complete degradation. Such a biodegradable ion-exchange drug carrier provides an effective and versatile strategy for enhancing long-term therapeutic responses of various local chemotherapy treatments.
研究领域:
药学
·
生物医学工程
·
肿瘤学
·
材料科学
✓ 已验证
DOI
PubMed
高影响因子
Bioactive Materials
·
2021
·
IF 14.593
Xiaohong Li,Xiongfa Ji,Kun Chen,Muhammad Wajid Ullah,Basen Li,Jiameng Cao,Lin Xiao,Jun Xiao,Guang Yang
Trans -catheter arterial embolization (TAE) plays an important role in treating various diseases. The available embolic agents lack X-ray visibility and do not prevent the reflux phenomenon, thus hindering their application for TAE therapy. Herein, we aim to develop a multifunctional embolic agent that combines the X-ray radiopacity with local procoagulant activity. The barium sulfate nanoparticles (BaSO 4 NPs) were synthesized and loaded into the polyvinyl alcohol/chitosan (PVA/CS) to prepare the radiopaque BaSO 4 /PVA/CS microspheres (MS). Thereafter, thrombin was immobilized onto the BaSO 4 /PVA/CS MS to obtain the thrombin@BaSO 4 /PVA/CS MS. The prepared BaSO 4 /PVA/CS MS were highly spherical with diameters ranging from 100 to 300 μm. In vitro CT imaging showed increased X-ray visibility of BaSO 4 /PVA/CS MS with the increased content of BaSO 4 NPs in the PVA/CS MS. The biocompatibility assessments demonstrated that the MS were non-cytotoxic and possessed permissible hemolysis rate. The biofunctionalized thrombin@BaSO 4 /PVA/CS MS showed improved hemostatic capacity and facilitated hemostasis in vitro . Additionally, in vivo study performed on a rabbit ear embolization model confirmed the excellent X-ray radiopaque stability of the BaSO 4 /PVA/CS MS. Moreover, both the BaSO 4 /PVA/CS and thrombin@BaSO 4 /PVA/CS MS achieved superior embolization effects with progressive ischemic necrosis on the ear tissue and induced prominent ultrastructural changes in the endothelial cells. The findings of this study suggest that the developed MS could act as a radiopaque and hemostatic embolic agent to improve the embolization efficiency.
研究领域:
生物医学工程
·
药学
·
医学影像
·
生物材料
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Bioactive Materials
·
2025
·
IF 20.3
Yitong Zhou,Menghui Liu,Chuandong He,Jiayuan Lin,Yanlv Chen,Mingyu Yu,Yuhan Jiang,Xin Peng
Current liquid embolic agents face several challenges, including poor biocompatibility and vascular recanalization. Herein, we propose an innovative liquid embolic agent composed of a coenzyme-based polymer (poly lipoic acid, PLA) and a biocompatible solvent (deep eutectic solvent, DES). The agent undergoes phase transformation to form a stable hydrogel in situ through solvent exchange with water, thereby enabling safe and effective embolization. First, DES is obtained by heating a mixture of choline chloride (ChCl) and glycerol (Gly). Subsequently, lipoic acid (LA) is incorporated into the DES and heated to produce the PLA/DES complex. Owing to the strong hydrogen bonding between the DES and PLA, the DES acts as a solvent while also inhibiting PLA depolymerization. Upon contact with blood, most of the DES exchange with water, whereas some amount of ChCl integrates within the PLA via strong hydrogen bonding. This hydrogen bonding not only prevents PLA depolymerization but also reinforces the PLA network, resulting in a stable PLA hydrogel rather than depolymerized LA monomers. Furthermore, liquid-metal (LM) nanoparticles are incorporated to fabricate radiopaque PLA/LM/DES. PLA/LM/DES shows better in vitro hemocompatibility and cytocompatibility, milder inflammatory response in a rat model, and more effective and safer embolization in a rabbit model than a commercial embolic agent (Onyx). Thus, this work provides an innovative liquid embolic agent and broadens the biomedical applications of DES.
研究领域:
生物材料
·
生物医学工程
·
材料科学
·
血管医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
POLYMER BULLETIN
·
2022
·Vol. 80
·期 3
·2697-2711
·
IF 2.843
Yin Peinan,Wei Chengxiong,Jin Xin,Yu Xiaogang,Wu Chengwei,Zhang Wei
Trans-catheter arterial embolization, as a minimally invasive therapy strategy, has become a choice for treating liver cancer. Development of embolic agents integrated with therapy and imagining functions is desired. Herein, magnetic polyvinyl alcohol (PVA) microspheres as embolic agents are prepared by emulsification method. The diameter of the magnetic PVA microspheres ranges from 10 to 110 μm, and the required size can be obtained by sieving. The temperature of magnetic PVA microspheres suspension could stabilize at 49 °C under the applied magnetic field, which indicates the microspheres have self-regulating temperature hyperthermia characteristic due to the application of magnetic nanoparticles with low Curie point. In addition, magnetic PVA microspheres possess obvious contrast effects on CT and T2-weighted imaging due to the existence of magnetic nanoparticles. Cytotoxicity assay indicates the survival rate of cells cultured with leach liquor of 30 mg/mL PVA/MNPs microspheres is 97.4%, which shows the magnetic microspheres have good cell biocompatibility. The developed magnetic microspheres have the potential to realize embolization, self-regulating temperature hyperthermia, and CT/MR imaging simultaneously in interventional therapy.
研究领域:
医学成像
·
癌症治疗
·
生物医学工程
·
材料科学
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2019
·
IF 4.784
Guobao Chen,Runan Wei,Xiang Huang,Fuping Wang,Zhongmin Chen
Transcatheter arterial chemoembolization (TACE) is well known as an effective treatment for hepatocellular carcinoma (HCC). In the present study, a novel embolic agent of sodium alginate (SA)-modified silk fibroin (SF) microspheres was successfully prepared by emulsifying cross-linking method. The SA-modified SF microspheres were evaluated for the ability of embolization by investigating the morphology, particle size, swelling ratio, degradation, cytotoxicity, blood compatibility, and in vivo embolization. The results found that SA-modified SF microspheres had smooth surfaces and good sphericity. Swelling ratio of the microspheres can meet the requirements of arterial embolic agent and have pH and temperature sensitivity. Furthermore, hemolytic and anticoagulant studies have proved that the microspheres have good blood compatibility. Cytotoxicity tests indicated that the microspheres could promote the proliferation of fibroblasts and HUVEC. In vivo embolization evaluation of microspheres revealed that the arteries could be embolized by SA-modified SF microspheres in 3 weeks. The ability of drug loading and releasing of microspheres was proved by the controlled release profile of Adriamycin hydrochloride. The findings indicated that the SA-modified SF microspheres can be used as a potentially biodegradable arterial embolic agent for liver cancer therapy.
研究领域:
生物医学工程
·
药学
·
癌症研究
✓ 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）