INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2021
·
IF 6.953
Kaipei Luo,Feng Xu,Tianyi Yao,Jianping Zhu,Hua Yu,Guangji Wang,Juan Li
Multidrug resistance (MDR) remains the primary issue leading to the failure of chemotherapy. In this study, a d-α-tocopherol polyethylene 1000 glycol succinate (TPGS) and chondroitin sulfate (CS) dual-modified lipid-albumin nanosystem was constructed for targeted delivery of paclitaxel (PTX) in treating MDR cancer. The obtained nanosystem (TLA/ [email protected] ) had an average size of around 176 nm and a negative zeta potential of around −18 mV. TPGS was confirmed to improve the intracellular accumulation of PTX and facilitate the mitochondrial-targeting of lipid-albumin nanosystem. Functionalized with the outer CS shell, TLA/ [email protected] entered MDR breast cancer (MCF-7/MDR) cells via CD44 receptor-mediated endocytosis. CS shell was degraded by concentrated hyaluronidase in the lysosomes, thereby releasing PTX into cytoplasm and inhibiting cell proliferation. In vivo studies revealed that TLA/ [email protected] possessed prolonged blood circulation, resulting in elevated tumor accumulation, excellent antitumor efficacy with a tumor inhibition ratio of 75.3%, and significant survival benefit in MCF-7/MDR tumor-bearing mice. Hence, this TPGS and CS dual-modified lipid-albumin nanosystem provides a promising strategy for targeted delivery of chemotherapeutic drug and reversal of MDR in cancer treatment.
研究领域:
药剂学
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肿瘤学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
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2014
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IF 8.312
Gan Tian,Xiaopeng Zheng,Xiao Zhang,Wenyan Yin,Jie Yu,Dongliang Wang,Zhiping Zhang,Xiangliang Yang,Zhanjun Gu,Yuliang Zhao
Multi-drug resistance (MDR) is a major cause of failure in cancer chemotherapy. Tocopheryl polyethylene glycol 1000 succinate (TPGS) has been extensively investigated for overcoming MDR in cancer therapy because of its ability to inhibit P-glycoprotein (P-gp). In this work, TPGS was for the first time used as a new surface modifier to functionalize NaYbF 4 :Er upconversion nanoparticles (UNCPs) and endowed the as-prepared products (TPGS-UCNPs) with excellent water-solubility, P-gp inhibition capability and imaging-guided drug delivery property. After the chemotherapeutic drug (doxorubicin, DOX) loading, the as-formed composites (TPGS-UCNPs-DOX) exhibited potent killing ability for DOX-resistant MCF-7 cells. Flow-cytometric assessment and Western blot assay showed that the TPGS-UCNPs could potently decrease the P-gp expression and facilitate the intracellular drug accumulation, thus achieving MDR reversal. Moreover, considering that UCNPs process efficient upconversion emission and Yb element contained in UCNPs has strong X-ray attenuation ability, the as-obtained composite could also serve as a dual-modal probe for upconversion luminescence (UCL) imaging and X-ray computed tomography (CT) imaging, making them promising for imaging-guided cancer therapy.
研究领域:
生物医学工程
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纳米医学
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癌症治疗
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
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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
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癌症研究
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药物递送系统
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产品关联
DOI
PubMed
高影响因子
Polymer Chemistry
·
2018
·Vol. 9
·期 14
·1827-1839
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IF 4.927
Tengfei Liu,Xiaoyan Liu,Hui Xiong,Cheng Xu,Jianxu Yao,Xiumei Zhu,Jianping Zhou,Jing Yao
D-α-Tocopheryl polyethylene glycol 1000 succinate (TPGS) and TPGS based conjugates have been widely researched for treatment of multidrug-resistant (MDR) cancer. Nevertheless, the influence of structural modification of TPGS on its properties and function requires further exploration. In this study, a hypothesis for the interaction between TPGS and P-glycoprotein (P-gp) at the molecular level has been proposed based on the existing limited knowledge of TPGS inhibition on P-gp. Two TPGS derivatives, TPGS–glycyrrhetinic acid conjugate (TGA) and TPGS–lactobionic acid conjugate (TLA), were synthesized. Molecular docking and molecular dynamics (MD) simulations were employed to investigate the P-gp inhibitory ability of TPGS and its derivatives and their inhibitory mechanism. Moreover, a systematic in vitro experiment was conducted to further confirm simulation results and evaluate antitumor effects. It was found that TLA and TGA displayed higher binding affinities with P-gp than TPGS, which was attributed to their properties of hydrophilicity and negative charge. Meanwhile, TPGS and its derivatives prevented the P-gp ATPase from hydrolyzing ATP by blocking the ATP binding sites, thereby inhibiting P-gp function. It was also found that the high hydrophilic–lipophilic balance (HLB) of the polymer contributed to a significant MDR reversing effect. In addition, TLA and TGA could promote intercellular accumulation and noticeably enhance the cytotoxicity of DOX in HepG2 and HepG2/ADR cells compared to TPGS. This work may be an important step in understanding the structure–activity relationships (SARs) of TPGS and its derivatives, the roles of the three polymers in MDR reversal mechanisms and in designing promising excipients for reversing MDR. The results suggested that TLA and TGA can be used as potential P-gp inhibitors or nanocarriers in the field of drug delivery.
研究领域:
药理学
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肿瘤学
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分子生物学
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药物递送系统
✓ 已验证
产品关联
DOI
高影响因子
RSC Advances
·
2024
·Vol. 14
·期 35
·25289-25300
·
IF 3.9
Jian-jun Zhang,Qiu-shui Luo,Qing-qing Li,Qian Xu,Xiang Geng,Jian-hua Xiong
Chlorogenic acid (CGA), a polyphenol compound, exhibits excellent anti-oxidative, anti-hypoxic, antibacterial, antiviral, and anti-inflammatory activities, however the bioactivity of it has not been fully utilized in vivo due to its instability and low bioavailability. To address these issues, we prepared and characterized CGA-TPGS-LP, which is a TPGS-modified liposome loaded with CGA. The pharmacokinetics of CGA-TPGS-LP were studied in rats after oral administration. CGA-TPGS-LP was fabricated using a combination of thin film dispersion and ion-driven methods. The liposomes were observed to be uniformly small and spherical in shape. Their membranes were composed of lecithin, cholesterol, and TPGS lipophilic head with a TPGS hydrophilic tail chain coating on its surface. The loading efficiency and encapsulation efficiency were found to be 11.21% and 83.22%, respectively. The physicochemical characterisation demonstrated that the CGA was present in an amorphous form and retained its original structural state within the liposomal formulation. The stability of CGA was significantly improved by fabricating TPGS-LP. CGA-TPGS-LP exhibited good sustained-release properties in both simulated gastric and intestinal fluids. Following oral administration, ten metabolites were identified in rat plasma using UPLC-QTOF-MS. UPLC-QqQ-MS/MS quantitative analysis demonstrated that the oral bioavailability of CGA encapsulated in TPGS-modified liposomes was enhanced by 1.52 times. In addition, the three main metabolites of CGA had higher plasma concentrations and slower degradation rate. These results demonstrate that TPGS-modified liposomes could be a feasible strategy to further enhance the oral bioavailability of CGA, facilitating its clinical use.
研究领域:
药剂学
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药理学
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分析化学
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药物递送系统
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产品关联
DOI
PubMed
高影响因子
Small
·
2017
·Vol. 13
·期 29
·1700623
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IF 8.643
Wei Cheng,Chaoyu Liang,Lv Xu,Gan Liu,Nansha Gao,Wei Tao,Lingyan Luo,Yixiong Zuo,Xusheng Wang,Xudong Zhang,Xiaowei Zeng,Lin Mei
A nanocarrier system of d -a-tocopheryl polyethylene glycol 1000 succinate (TPGS)-functionalized polydopamine-coated mesoporous silica nanoparticles (NPs) is developed for sustainable and pH-responsive delivery of doxorubicin (DOX) as a model drug for the treatment of drug-resistant nonsmall cell lung cancer. Such nanoparticles are of desired particle size, drug loading, and drug release profile. The surface morphology, surface charge, and surface chemical properties are also successfully characterized by a series of techniques such as transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), Brunauer-Emmett-Teller (BET) method, thermal gravimetric analysis (TGA), dynamic light scattering (DLS), and Fourier transform infrared spectroscopy (FTIR). The normal A549 cells and drug-resistant A549 cells are employed to access the cytotoxicity and cellular uptake of the NPs. The therapeutic effects of TPGS-conjugated nanoparticles are evaluated in vitro and in vivo. Compared with free DOX and DOX-loaded NPs without TPGS ligand modification, MSNs-DOX@PDA-TPGS exhibits outstanding capacity to overcome multidrug resistance and shows better in vivo therapeutic efficacy. This splendid drug delivery platform can also be sued to deliver other hydrophilic and hydrophobic drugs.
研究领域:
纳米技术
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药剂学
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癌症研究
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材料科学
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DOI
PubMed
高影响因子
JOURNAL OF DRUG TARGETING
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2025
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IF 3.9
Jiaying Li,Tingyuan Li,Mingjie Gong,Xiaowen Wang,Qinyang Hua,Xia Jiang,Qilong Wang,Elmurat Toreniyazov,Jiangnan Yu,Xia Cao,Michael Adu-Frimpong,Ximing Xu
Phloretin exhibits strong antioxidant and anti-ageing properties by inhibiting mitochondrial oxidation of glutamate, succinic acid, and ascorbic acid. However, its clinical application is limited by poor aqueous solubility and low oral bioavailability. To enhance its bioavailability and efficacy, we incorporated phloretin into nano-micelles (phloretin-MM) using the thin film dispersion method. Characterisation revealed that the optimal formulation had TPGS and Pluronic F68 in a 4:1 ratio as the excipients, which resulted in spherical micelles with an average particle size of 33.28 nm and an encapsulation efficiency of 71.2 ± 0.48%. The in vitro release profile showed that the phloretin-MM showed significantly higher cumulative release rates than free phloretin across various pH conditions, while the pharmaceutical analysis in rats indicated that phloretin-MM significantly improved the oral bioavailability of phloretin (about 5 folds) in circulation. Additionally, through the analysis of the staining of zebrafish under light microscopy and the average gray value, it can be concluded that phloretin has anti-ageing drug effect, and phloretin-MM is better than free phloretin. These findings suggest that TPGS/Pluronic F68-modified phloretin-MM could serve as an excellent nano-drug carrier system, potentially enhancing the solubility, bioavailability, and anti-ageing effects of phloretin for broader clinical applications.
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产品关联
DOI
PubMed
高影响因子
Nanomedicine
·
2019
·
IF 4.717
Tengfei Liu,Yudi Deng,Jianxu Yao,Hui Xiong,Jing Yao
Aim: Multidrug resistance and severe side effects lead to poor therapeutic efficacy of monotherapy against hepatocellular carcinoma. Here, a targeting codelivery nanocomposite system is constructed to reverse tumor multidrug resistance and realize a combination therapy of doxorubicin and oxaliplatin. Methods & materials: We simulate the composited structure of TPGS-lactobionic acid conjugate (TLA) modified methyl poly(ethylene glycol)-polylactide (mPP) polymersomes using dissipative particle dynamics. Cellular uptake and drug retention, cytotoxicity, in vivo antitumor efficacy and toxicity were evaluated. Results: TLA/mPP composited polymersomes improved intracellular accumulation of coloaded drugs via active targeting ability and P-gp efflux inhibition, leading to strong cytotoxicity against HepG2/ADR cells and potent tumor inhibition (93.5%) for HepG2/ADR tumor. Conclusion: TLA/mPP composited polymersomes represent a promising multifunctional nanoplatform against hepatocellular carcinoma.Graphical abstract
研究领域:
药理学
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肿瘤学
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纳米技术
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分子生物学
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DOI
PubMed
高影响因子
RSC Advances
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2016
·Vol. 6
·期 34
·28331-28342
·
IF 3.289
Lu Wang,Xi Xie,Di Liu,Xiao-Bin Fang,Peng Li,Jian-Bo Wan,Cheng-Wei He,Mei-Wan Chen
Reduction-sensitive micelles with crosslinked cores were developed to load the lipophilic chemotherapeutic drug docetaxel (DTX) in order to overcome the issues of toxicity, water insolubility, and rapid metabolism of DTX. These DTX-loaded micelles (MM(DTX/Crosslink)) provide efficient incorporation and sustained release of DTX. Using independently synthesized LA–PLGA–TPGS and DSPE–PEG polymers as vehicles, MM(DTX/Crosslink) was found to be reduction-responsive, and possessed desirable drug entrapment efficiency (84.17 ± 1.15%) and drug loading efficiency (6.21 ± 0.07%). The MM(DTX/Crosslink) quickly dissociated under reduction conditions that mimicked the reductive intracellular environment, suggesting that it can rapidly release the encapsulated DTX in vitro. Furthermore, to target MM(DTX/Crosslink) to tumors for cancer therapy, iRGD was conjugated to the surface of MM(DTX/Crosslink). The iRGD-MM(DTX/Crosslink) micelles significantly increased the cellular uptake of DTX and inhibited cell proliferation, compared to the micelles without iRGD modification. Moreover, the iRGD-MM(DTX/Crosslink) micelles presented enhanced antitumor effects based on the analyses of apoptosis and cell cycle arrest. The micelles developed in this work may constitute a stable, efficient, and powerful system to deliver DTX into cancer cells.
研究领域:
药剂学
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肿瘤学
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生物材料学
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产品关联
DOI
高影响因子
MOLECULAR PHARMACEUTICS
·
2013
·
IF 4.57
Yuanyuan Guo,Min Chu,Songwei Tan,Shuang Zhao,Hanxiao Liu,Ben Oketch Otieno,Xiangliang Yang,Chuanrui Xu,Zhiping Zhang
To overcome the P-glycoprotein (P-gp)-induced multidrug resistance (MDR) of cancer cells, a novel copolymer, chitosan-graft-d-α-tocopheryl polyethylene glycol 1000 (TPGS) (CT) was synthesized for doxorubicin (DOX) delivery by the P-gp inhibiting virtue of TPGS. DOX-loaded CT nanoparticles (NPs) were fabricated by a modified solvent extraction/evaporation method combined with ionic cross-linking to form a uniform particle size of 140–180 nm with ∼40% DOX loading efficiency. These drug-loaded CT NPs demonstrated a pH-responsive release behavior, and DOX was released more quickly under low pH values. Significant cell cytotoxicity was observed on the human hepatocarcinoma cells (HepG2 and BEL-7402) and human breast adenocarcinoma cells (MCF-7). The cell cytotoxicity and apoptosis of drug-resistant cells (MCF-7/DOX and BEL-7402/5-Fu), was greatly enhanced as compared to Adriamycin. The IC50 value showed that DOX-loaded CT NPs could be 1.5–199-fold more effective than Adriamycin. This can be attributed to the P-gp blocking and down-regulation of ATP levels by the CT NPs. The potential of these NPs to act as an oral delivery system was also investigated. Both the pharmacokinetic properties and in vivo antitumor activity of DOX-loaded CT NPs were improved compared with Adriamycin.
研究领域:
药学
·
生物医学工程
·
肿瘤学
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY
·
2022
·
IF 3.727
Xinyi Shen,Wanjing Rong,Michael Adu-Frimpong,Qing He,Xiaoxiao Li,Feng Shi,Hao Ji,Elmurat Toreniyazov,Xiaoli Xia,Jian Zhang,Qilong Wang,Jiangnan Yu,Ximing Xu
Purpose To prepare polyethylene glycol succinate-vitamin E modified pinocembrin (PCB)-loaded liposomes (PCBT-liposomes) and evaluate PCBT-liposomal pharmacokinetics and antihyperglycemic activity.Significance The novel PCBT-liposomes demonstrated a promising application prospect as a nano drug carrier for future research.Methods Thin film dispersion was used to prepare PCBT-liposomes. We measured a series of characterization, followed by in vitro cumulative release, in vivo pharmacokinetic study, and antihyperglycemic activity evaluation.Results PCBT-liposomes displayed spherical and bilayered nanoparticles with mean particle size (roughly 92 nm), negative zeta potential (about −26.650 mV), high drug encapsulation efficiency (87.32 ± 1.34%) and good storage (at 4 or 25 °C) stability during 48 h after hydration. The cumulative release rate of PCBT-liposomes was markedly higher than free PCB in four different pH media. In vivo investigation showed that PCBT-liposomes could obviously improve oral bioavailability of PCB by 1.96 times, whereas the Cmax, MRT0–t, and T1/2 of PCBT-liposomes were roughly 1.700 ± 0.139 µg·mL−1, 12.695 ± 1.647 h, and 14.244 h, respectively. In terms of biochemical analysis, aspartate amino-transferase (AST), alanine amino-transferase (ALT), interleukin-1 (IL-1), and tumor necrosis factor-α (TNF-α) concentrations in serum of diabetic mice were respectively decreased 28.28%, 17.23%, 17.77%, and 8.08% after PCBT-liposomal treatment.Conclusion These results show PCBT-liposomal preparation as an excellent nano-carrier which has the potential to improve water solubility, bioavailability, and antihyperglycemic activity of PCB, amid broadening the application of PCB in the clinical settings.
研究领域:
药剂学
·
药理学
·
纳米技术
·
糖尿病研究
✓ 已验证
DOI
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2016
·
IF 3.994
Jinli Li,Xudong Cheng,Yan Chen,Weiming He,Li Ni,Peihua Xiong,Minggang Wei
Luteolin (LUT) is an active agent in cancer prevention and a potential candidate for clinical chemotherapy. However, poor water solubility and extensive excretion have limited the clinical use of luteolin. Herein, we attempted to develop vitamin E d-α-tocopherol acid polyethylene glycol 1000 succinate (TPGS) coated liposomes to improve the accumulation of luteolin in lung cancer. Luteolin or coumarin-6 loaded liposomes were prepared using film-dispersion methods and characterized according to their particle size, polydispersity, zeta potential , and drug encapsulation efficiency. Cellular uptake properties and cytotoxicities of luteolin or coumarin-6 loaded liposomes were determined in A549 cells. Optical in vivo imaging was employed as a method of assessing tumor targeting. The antitumor effect was evaluated in mice xenotransplanted with A549 cancer cells. The results showed that TPGS coated liposomes are spherical, and are ∼176.2 nm in size. TPGS coated liposomes enhanced cellular uptake and apoptosis by upregulating the Bax/Bcl-2 ratio, resulting in improved cytotoxicity in A549 cells. TPGS coated liposomes significantly accumulated in tumor tissue and enhanced tumor inhibition without altering the structures of other organs. Thereby, TPGS coated liposomes provide an effective strategy in cancer chemotherapy for model drugs with poor water solubility such as luteolin.
研究领域:
药剂学
·
肿瘤学
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药物递送系统
·
纳米技术
✓ 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）