CARBOHYDRATE POLYMERS
·
2017
·
IF 4.811
Yangjian Chen,Fujun Peng,Xiaoda Song,Jicheng Wu,Wenbin Yao,Xiangdong Gao
Polymer-based paclitaxel (PTX) conjugates have demonstrated application potentials to improve the water solubility and enhance the efficiency of drug delivery. In this study, a novel HA-based drug conjugate, HA-6-PTX, was designed and successfully synthesized by chemically grafting PTX to the C-6 position of N -acetyl- d -glucosamine (GlcNAc) of hyaluronic acid (HA) using hexanediamine as the linker. Leaving the carboxylate of HA chain unaffected, the conjugate with drug loading as high as 21.8% showed an excellent water solubility of 168 mg/mL and exhibited increased drug release in the presence of hyaluronidase. Compared to free PTX, HA-6-PTX demonstrated increased cytotoxicity and enhanced apoptosis-inducing effect against HepG2 and A549 cells due to the increased cellular uptake of drug via HA-receptor mediated endocytosis. It was concluded that the HA-6-PTX conjugate could be potentially utilized for further exploration as targeted drug delivery to enhance antitumor efficacy.
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MACROMOLECULAR BIOSCIENCE
·
2016
·Vol. 16
·期 5
·774-783
·
IF 3.68
Tieshi Wang,Xinde Tang,Jingtian Han,Yuanyuan Ding,Wenjuan Guo,Meishan Pei
Biodegradable self-assembled polymeric nanoparticles (NPs) composed of poly(6- O -methacryloyl-D-galactopyranose)- b -poly(L-lactide)- b -poly(6- O -methacryloyl-D-galactopyranose) (PMAGP- b -PLA- b -PMAGP) are prepared as carriers for the hydrophobic anticancer drug paclitaxel (PTX), to achieve target delivery to hepatoma cells. PTX can be encapsulated by the NPs with various molar ratios of L-lactide (LA) and 6- O -methacryloyl-D-galactopyranose (MAGP) during the process of self-assembly, and the resulting NPs exhibit high drug loading efficacy and substantial stability in aqueous solution. The size, size distribution, and morphology of the NPs are characterized using a Zetasizer Nano ZS and transmission electron microscopy. The hemolysis assay and cell cytotoxicity assay indicate that the polymeric NPs are biocompatible and non-toxic. The cellular uptake assay demonstrates that the galactose-containing NPs can be selectively recognized and subsequently accumulate in HepG2 cells. All of these results demonstrate that galactose-containing polymeric NPs are potential carriers for hepatoma-targeted drug delivery and liver cancer therapy in clinical medicine.
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DRUG DELIVERY
·
2016
·
IF 4.843
Chang Li,Yan Shen,Chunmeng Sun,Nihad Cheraga,Jiasheng Tu
To investigate the physicochemical properties, immunosafety and chronic toxicity of monomethoxypoly(ethylene glycol)-b-poly(lactic acid) (mPEG-PLA), a copolymer used as a carrier for paclitaxel (PTX) delivery. The H-Nuclear Magnetic Resonance (H-NMR), dynamic light scattering and fluorescence probe technique were conducted to determine the physicochemical properties of mPEG-PLA copolymer. PTX-loaded polymeric micelles were characterized regarding their particle size, entrapment efficiency (EE), drug loading (DL), in vitro drug release and hemolysis rate. The complement activation in human serum and mast cells degranulation were performed by ELISA and RBL-2H3 cell line in vitro, respectively. The chronic toxicity study was carried out on beagle dogs. The optimized PTX-loaded mPEG-PLA (40/60) micelles showed a particle size of 37 nm and EE of 98.0% with a DL of 17.0% w/w. Transmission electron microscopy (TEM) analyses showed that mPEG-PLA (40/60) micelles have spherical shape with dense core. In vitro release study showed a sustained release for 24 h, and the hemolysis study revealed that mPEG-PLA (40/60) was a safe nanocarrier for intravenous administration. mPEG-PLA (40/60) showed a lower complement activation ability compared to mPEG-PLA (50/50) and Cremophor® EL (Cr EL). Furthermore, the chronic toxicity of PTX-loaded mPEG-PLA (40/60) micelles was significantly lower than those of mPEG-PLA (50/50) and Cr EL.
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COLLOIDS AND SURFACES B-BIOINTERFACES
·
2017
·
IF 3.887
Fuqiang Guo,Jiajia Shang,Hai Zhao,Kangrong Lai,Yang Li,Zhongxiong Fan,Zhenqing Hou,Guanghao Su
As one of nanomedicine delivery systems (NDSs), drug nanocrystals exhibited an excellent anticancer effect. Recently, differences of internalization mechanisms and subcellular localization of both drug nanocrystals and small molecular free drug have drawn much attention. In this paper, paclitaxel (PTX) as a model anticancer drug was directly labeled with 4-chloro-7-nitro-1, 2, 3-benzoxadiazole (NBD-Cl) (a drug-fluorophore conjugate Ma et al. (2016) and Wang et al. (2016) [1,2] (PTX-NBD)). PTX-NBD was synthesized by nucleophilic substitution reaction of PTX with NBD-Cl in high yield and characterized by fluorescence, XRD, ESI–MS, and FT-IR analysis. Subsequently, the cube-shaped PTX-NBD nanocrystals were prepared with an antisolvent method followed by surface functionalization of SPC and MPEG-DSPE. The obtained specific shaped [email protected] NCs had a hydrodynamic particle size of ∼50 nm, excellent colloidal stability, and a high drug-loading content of ∼64%. Moreover, in comparison with free PTX-NBD and the sphere-shaped PTX-NBD nanocrystals with surface functionalization of SPC and MPEG-DSPE ( [email protected] NSs), [email protected] NCs remarkably reduced burst release and improved cellular uptake efficiency and in vitro cancer cell killing ability. In a word, the work highlights the potential of theranostic prodrug nanocrystals based on the drug-fluorophore conjugates for cell imaging and chemotherapy.
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BIOMATERIALS
·
2011
·
IF 7.883
Jing Li,Meirong Huo,Jing Wang,Jianping Zhou,Jumah M. Mohammad,Yinlong Zhang,Qinnv Zhu,Ayman Y. Waddad,Qiang Zhang
A targeted intracellular delivery system of paclitaxel (PTX) was successfully developed based on redox-sensitive hyaluronic acid-deoxycholic acid (HA-ss-DOCA) conjugates. The conjugates self-assembled into nano-size micelles in aqueous media and exhibited excellent drug-loading capacities (34.1%) and entrapment efficiency (93.2%) for PTX. HA-ss-DOCA micelles were sufficiently stable at simulated normal physiologic condition but fast disassembled in the presence of 20 m m reducing agent, glutathione . In vitro drug release studies showed that the PTX-loaded HA-ss-DOCA micelles accomplished rapid drug release under reducing condition. Intracellular release of fluorescent probe nile red indicated that HA-ss-DOCA micelles provide an effective approach for rapid transport of cargo into the cytoplasm. Enhanced cytotoxicity of PTX-loaded HA-ss-DOCA micelles further confirmed that the sensitive micelles are more potent for intracellular drug delivery as compared to the insensitive control. Based on flow cytometry and confocal microscopic analyses, observations revealed that HA-ss-DOCA micelles were taken up to human breast adenocarcinoma cells (MDA-MB-231) via HA-receptor mediated endocytosis . In vivo investigation of micelles in tumor-bearing mice confirmed that HA-ss-DOCA micelles possessed much higher tumor targeting capacity than the insensitive control. These results suggest that redox-sensitive HA-ss-DOCA micelles hold great potential as targeted intracellular delivery carriers of lipophilic anticancer drugs.
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EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
·
2012
·
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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ADVANCED FUNCTIONAL MATERIALS
·
2025
·
IF 19
Danping Wang,Shengyao Xu,Si Zheng,Rong Chai,Zhiyu Kuang,Yixin Sun,Yaqi Li,Shiyi Zuo,Xiang Gao,Xin Li,Qikun Jiang,Zhonggui He,Jin Sun,Hongrui Lei,Anhua Wang,Bingjun Sun
Paclitaxel (PTX) is an effective agent against a wide spectrum of solid tumors. Lipusu is the first and only marketed liposomal PTX product in the world. However, it is hindered by the insufficient affinity between PTX and phospholipids, resulted in a low drug loading (≈5.68%), poor stability, and limited antitumor efficacy. Inspired by the structural characteristics of phospholipids, a phospholipid-like PTX prodrug (PTX-OCT) is designed to construct prodrug liposomes (PTX-OCT PLs). Compared with Lipusu, PTX-OCT PLs possessed a smaller particle size (135 vs 400 nm) with a higher drug loading (10.52% vs 5.68%, equal to PTX). Meanwhile, PTX-OCT PLs would deliver PTX efficiently in vivo evidenced by the AUC higher than Lipusu (≈170-fold) due to their superior stability. The introduction of disulfide bonds endowed PTX-OCT PLs with the capacity of intelligent activation, which is the key element for tumor selectivity. With such characterizations, PTX-OCT PLs exhibited potent antitumor efficacy with good tolerance in 4T1-bearing model, even better than Abraxane and Lipusu. To summarize, this work designed PTX nanomedicines with potential market competitiveness and enriched the theoretical basis of designing advanced nanomedicines for efficient cancer treatment.
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CHEMICAL & PHARMACEUTICAL BULLETIN
·
2015
·Vol. 63
·期 2
·68-74
·
IF 1.164
Wen Lv,Lihua Cheng,Baohua Li
One of the major obstacles to successful paclitaxel (PTX) chemotherapy is toxic side effects, which are often due to the conventional surfactants used, such as Cremophor EL. PTX is characterized by its hydrophobicity and insolubility, which limit its application in ovarian cancer therapy. The aim of this study was to develop Cremophor EL-free PTX-loaded methoxy poly(ethylene glycol)-block-(lactic-co-glycolic acid) copolymers (PLGA-mPEG) nanoparticles (NPs) using d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) as a novel emulsifier. The ability of nanoparticles loaded with paclitaxel (NP-PTX) to inhibit tumor growth was assessed in vitro and in vivo. The acute toxicity of NP-PTX was also evaluated in vivo. We found that paclitaxel was efficiently encapsulated into PLGA-mPEG NPs with a low concentration of TPGS as the emulsifier. The synthesized NP-PTX demonstrated the desired diameter of 80 nm as characterized by transmission electron microscopy. The NP-PTX also exhibited a sustained release of loaded PTX over 4 d with the same chemotherapeutic efficiency and reduced side effects. NP-PTX-treated cells showed slightly lower cytotoxic responses compared with those treated with free PTX at the same concentration. In vivo studies confirmed that NP-PTX significantly enhanced the median lethal dose of paclitaxel by 10-fold, and a similar effect on the inhibition of tumor growth was achieved in nude mice.
研究领域:
药剂学
·
肿瘤学
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BIOMATERIALS
·
2014
·
IF 8.312
Shixian Lv,Zhaohui Tang,Mingqiang Li,Jian Lin,Wantong Song,Huaiyu Liu,Yubin Huang,Yuanyuan Zhang,Xuesi Chen
Despite progress, combination therapy of different functional drugs to increase the efficiency of anticancer treatment still remains challenges. An amphiphilic methoxy poly(ethylene glycol)- b -poly( l -glutamic acid)- b -poly( l -lysine) triblock copolymer decorated with deoxycholate (mPEsG- b -PLG- b -PLL/DOCA) was synthesized and developed as a nanovehicle for the co-delivery of anticancer drugs: doxorubicin (DOX) and paclitaxel (PTX). The amphiphilic copolymer spontaneously self-assembled into micellar-type nanoparticles in aqueous solutions and the blank nanoparticles possessed excellent stability. Three different domains of the copolymer performed distinct functions: PEG outer corona provided prolonged circulation, middle biodegradable and hydrophilic PLG shell was designed for DOX loading through electrostatic interactions , and hydrophobic deoxycholate modified PLL served as the container for PTX. In vitro cytotoxicity assays against A549 human lung adenocarcinoma cell line demonstrated that the DOX + PTX co-delivered nanoparticles (Co-NPs) exhibited synergistic effect in inducing cancer cell apoptosis. Ex vivo DOX fluorescence imaging revealed that Co-NPs had highly efficient targeting and accumulation at the implanted site of A549 xenograft tumor in vivo . Co-NPs exhibited significantly higher antitumor efficiency in reducing tumor size compared to free drug combination or single drug-loaded nanoparticles, while no obvious side effects were observed during the treatment, indicating this co-delivery system with different functional antitumor drugs provides the clinical potential in cancer therapy.
研究领域:
药学
·
纳米技术
·
肿瘤学
·
药物递送系统
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INORGANIC CHEMISTRY COMMUNICATIONS
·
2026
·
IF 5.9
Sahresh Majeed,Yumo Liu,Guanghui Cui,Abdul Majid Khan,Muhammad Irslan Ilyas,Xiaodong Wang,Wei Liu,Zhanpeng Wu
The persistent challenges of multidrug resistance and systemic toxicity in cancer chemotherapy necessitate the development of intelligent, tumor-targeted co-delivery systems. Herein we report a novel nickel-based metal-organic framework (CUR + PTX@Ni-MOF) engineered with a phosphazene-derived ligand for the pH-responsive co-delivery of paclitaxel (PTX) and curcumin (CUR). The framework integrates a hexachlorocyclotriphosphazene (HCCP)-based linker featuring an intrinsically acid-labile P3N3 core enabling controlled degradation within the acidic tumor microenvironment (TME). The Ni-MOF exhibits a high BET surface area (177.118 m 2 /g) and a mesoporous architecture facilitating exceptional dual-drug loading capacities of 56.15% for CUR (96.3% encapsulation efficiency, EE) and 26.18% for PTX (43.01% EE). In vitro release studies demonstrated minimal drug leakage at physiological pH (7.4), while triggered, sustained release was achieved under acidic conditions (pH 6.5 and 5.0) with maximum cumulative releases of 75.42% for CUR and 49.35% for PTX at pH 5.0. Cellular assays confirmed high biocompatibility with normal LO2 hepatocytes (>80% viability) and potent, synergistic cytotoxicity against HeLa cancer cells driven by enhanced cellular uptake and apoptosis induction. This work establishes CUR + PTX@Ni-MOF as a promising, intrinsically pH-responsive platform for targeted and synergistic combination chemotherapy.
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PHYTOTHERAPY RESEARCH
·
2026
·
IF 8.1
Yubo Zhang,Na Du,Yingqian Ci,Shuai Lu,Shasha Xu,Huajun Li,Chang Qing,Qiaoling Chen,Yongfei Wang,Feifei Chen,Jinping Qiao,Mei Han
Green tea, a commonly consumed beverage worldwide, is extensively used as dietary supplements for cancer prevention. However, the interaction between green tea and paclitaxel is still unknown. This study aimed to systematically investigate the herb-drug interaction of green tea consumption on the pharmacodynamics and pharmacokinetics of paclitaxel. The ATP assay results indicated that green tea extract (GTE) significantly enhanced the cytotoxicity of paclitaxel in both human and murine breast cancer cells. Further, the 4T-1 tumor model testified that daily green tea consumption could improve the therapeutic effects of paclitaxel on breast carcinoma. The pharmacokinetic profiles revealed that in the group with short-term green tea consumption (0.5 h), there was a more than 55.87% increase in the maximum plasma concentration ( C max ) of paclitaxel and a 38.49% increase in the area under the plasma concentration curve (AUC). In the long-term green tea consumption group (2 weeks), there was a 23.80% increase in the C max of paclitaxel and a 28.29% increase in the AUC. Moreover, long-term green tea consumption significantly reduced hepatic microsomal protein level. Taken together, green tea consumption enhances the anticancer efficacy and increases the pharmacokinetic profile of paclitaxel, which provides information to study the interaction between herbs and chemotherapy.
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Materials Today Bio
·
2025
·
IF 10.2
Manzhen Li,Likang Lu,Yaoyao Guo,Jingxin Fu,Ziqi Zhang,Pengxin Li,Yifei Guo,Meihua Han,Xiangtao Wang
Immunotherapy shows promise for tumor control but is limited by low response rates. Paclitaxel (PTX) induces immunogenic cell death (ICD), yet conventional delivery systems face challenges like low drug loading and insufficient intracellular accumulation, reducing ICD efficacy. Small-molecule self-assembled PTX nanoparticles offer a promising solution due to high drug loading and dose delivery. In this study, PTX was conjugated with phenylboronic acid (PBA) to form the derivative PTX-PBA, which spontaneously self-assembled with fructose into nanoparticles (PTX-PBA-Fru NPs). These nanoparticles exhibited a uniform size of 107.8 ± 2.9 nm, a PDI of 0.064 ± 0.042, and a zeta potential of -12.2 ± 0.9 mV, with spherical morphology. In 4T1 tumor-bearing mice, PTX-PBA-Fru NPs significantly enhanced tumor inhibition (p < 0.001) and increased body weight (p < 0.05). No allergic reactions in healthy Balb/c mice and the maximum tolerated intravenous dose reached 200 mg/kg, underscoring its favorable safety profile of PTX-PBA-Fru NPs. The ICD effects induced by PTX-PBA-Fru NPs, when combined with the immunomodulator resiquimod (R848), elicited a robust anti-tumor immune response. This combination therapy effectively remodeled the immunosuppressive tumor microenvironment and achieved a 37.5% tumor eradication rate. Moreover, it established long-term immune memory, providing protection against tumor re-challenge. This novel PTX formulation demonstrates strong anti-tumor effects, safety, and clinical potential in combination with R848-based immunotherapy.
研究领域:
肿瘤学
·
药剂学
·
免疫学
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