JOURNAL OF PHARMACEUTICAL SCIENCES
·
2025
·
IF 3.8
Ping-fu Huang,Wen-Min Niu,Lu-lu Liu,Guan-qiao Wang,Jun Chen,Zhou-xun Dong,Jia-bing Tong
Paclitaxel (PTX), categorized as a BCS Class IV anti-tumor agent, is integral to clinical treatment, however, the insolubility of PTX leads to diminished bioavailability. Resveratrol (RES), a bioactive compound present in various dietary sources, has the potential to augment the anti-tumor effectiveness of PTX. This research aims to formulate a co-amorphous system consisting of PTX and RES to enhance the solubility and bioavailability of PTX. The co-amorphous system was synthesized via the solvent evaporation technique and subsequently characterized using powder X-ray diffraction, Fourier-transform infrared spectroscopy, differential scanning calorimetry, Raman spectroscopy, and thermal analysis. Molecular dynamics simulations illustrated the interactions between PTX and RES, which facilitated an increase in apparent solubility and in vitro dissolution rates. Furthermore, in vitro cytotoxicity assays, Caco-2 cell model studies, and in vivo anti-tumor experiments demonstrated that the PTX-RES combination exhibited enhanced anti-tumor efficacy relative to other treatment groups. Pharmacokinetic evaluations revealed that the oral bioavailability of the PTX-RES complex surpassed that of pure PTX. These findings substantiate that the PTX-RES co-amorphous system significantly improves the physicochemical properties and anti-tumor activity of PTX. Additionally, this study presents a promising approach for enhancing the solubility and bioavailability of compounds with poor solubility.
研究领域:
药学
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHARMACOLOGICAL RESEARCH
·
2025
·
IF 10.5
Huan Shi,Biaobiao Wang,Zhiwei Shi,Huilin Ma,Yunmei Li,Ying Liu,Yu Zhao,Nan Xia,Chao Wu,Yu Gao
Glioma, the most prevalent primary intracranial tumor, presents significant clinical treatment challenges due to its high invasiveness and therapeutic resistance. Therefore, the development of a targeted therapeutic agent that is both highly effective and low in toxicity is crucial. In this research, we aimed to design a bionic mesoporous selenium nanoparticle (ACMLMSeP) functionalized with paclitaxel and Ang-2 for nasal administration as a targeted treatment approach for glioma. Nasal administration facilitates direct delivery of drugs to the brain through the olfactory nerve, thereby circumventing the protective mechanisms of the blood-brain barrier. Mesoporous selenium (MSe) significantly enhances the loading capacity for insoluble drugs while improving their water solubility. The functionalization of MSe enables slow drug release and facilitates targeted drug accumulation. Moreover, accumulated nano-selenium promotes reactive oxygen species (ROS) production, induces autophagy, and synergizes with drugs to accelerate apoptosis in tumor cells. Analysis using Transmission Electron Microscopy (TEM) images and Dynamic Light Scattering (DLS) indicated that ACMLMSe has an average particle size of roughly 135 nm. Results from in vitro release assessments indicated that the ACMLMSeP sustained the release of the drug, reaching a total release rate of 74.96 ± 2.34 % within 24 h. Cellular uptake studies and in vivo imaging showed the strong targeting capabilities of the ACMLMSeP nanoparticles. Furthermore, the results obtained from the MTT assays, flow cytometry analysis, immunofluorescence staining, and in vivo antitumor evaluations collectively revealed that ACMLMSeP effectively inhibited proliferation while promoting apoptosis in C6 cells. In summary, these experimental findings clearly suggest that ACMLMSeP may serve as a promising biomimetic nanosystem for the targeted treatment of brain glioma.
研究领域:
药学
·
肿瘤学
·
纳米医学
·
神经科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Cancer
·
2025
·Vol. 16
·期 13
·3842-3850
·
IF 3.2
Deng Yingyue,Zhang Tao,Zhou Jiaru,Su Zhihao,Cao Yingsong,Luo Junxi,Zhao Leming,Hua Junjie,Wang Guoqiang,Xiao Min,Ban Junfeng,Zhang Yan,Liang Hongcai
Nanoparticle carriers can selectively deliver the drug cargo to tumor cells, thus having the ability to prevent early drug release, reduce non-specific cell binding, and prolong in vivo drug retention. We constructed paclitaxel (PTX)-loaded lipid-shell mesoporous silica nanoparticles (LMSNs) for targeted anti-cancer drug delivery. The physical properties of PTX-LMSNs were analyzed by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The drug loading (DL%) and entrapment efficiency (EE%) of PTX-LMSNs were measured by high performance liquid chromatography (HPLC). In vitro drug release test, in vivo imaging, tissue distribution and pharmacokinetics of PTX-LMSNs were also evaluated. The SEM examination showed that MSNs were sphere, whereas TEM showed that they were rich in fine pores. The uniform core-shell structure of PTX-LMSNs was also verified by TEM. The DL capacity of PTX-LMSN was as high as 21.75%, and PTX was released from the nanoparticles in vitro in a pH-dependent manner. The cumulative amount of free PTX increased at lower pH, which is conducive to selective drug release from LMSNs in the acidic tumor tissues. In vivo imaging showed prolonged retention of PTX-LMSNs, which is beneficial to their therapeutic efficacy. In addition, PTX-LMSNs were primarily concentrated in the liver. Pharmacokinetic experiments showed that the half-life of PTX-LMSNs was 23.21% longer and 79.24% higher than that of Taxol. Together, LMSNs are a highly promising antineoplastic drug carrier system.
研究领域:
纳米技术
·
药剂学
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肿瘤学
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药物递送
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材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Signal Transduction and Targeted Therapy
·
2025
·Vol. 10
·期 1
·395
·
IF 52.7
Liu Yue,Wang Huirui,Zhan Jie,Sun Jiabo,Sun Yan,Fu Xiaojie,Lv Dongxue,Li Xiuyun,Dong Ting,Lou Hongxiang
The widespread clinical application of paclitaxel (PTX) in cancer treatment has been significantly limited by the emergence of drug resistance and the presence of drug-tolerant persister cells. To systematically identify key regulators of this resistance, we conducted a genome-wide CRISPR/Cas9 knockout screen, which revealed that cell division cycle 6 (CDC6) is a critical determinant of cell adhesion-mediated PTX resistance. Furthermore, our results illustrate that CDC6, an essential DNA replication licensing factor, functions through a pathway distinct from previously well-characterized resistance mechanisms. Genetic depletion of CDC6 considerably sensitizes cells, markedly increasing PTX-induced cell death. In addition to its established role in chromosome stability, CDC6 physically interacts with tropomodulin-3 (Tmod3) in the cytoplasmic compartment. This interaction enhances CDC6 protein stability and drives drug resistance phenotypes through the regulation of actin cytoskeleton remodeling and facilitating focal adhesion assembly. In addition, combination treatment with PTX and actin filament inhibitors synergistically enhanced the antitumor efficacy both in vitro and in vivo. Overall, our studies elucidate the mechanisms through which CDC6 functions as a key regulator of PTX resistance and provide a potential therapeutic strategy to increase PTX efficacy through the modulation of the cytoskeletal-adhesion axis.
研究领域:
癌症生物学
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分子肿瘤学
·
细胞信号传导
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药物耐药性
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细胞骨架动力学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2024
·Vol. 29
·期 16
·3733
·
IF 4.2
Leping He,Yuxi Tian,Qingqing Liu,Jiaolin Bao,Ren-Bo Ding
Colorectal cancer (CRC) is the second leading cause of cancer-related death worldwide. It is important to discover new therapeutic regimens for treating CRC. Depression is known to be an important complication of cancer diseases. Repurposing antidepressants into anticancer drugs and exploring the combinational efficacy of antidepressants and chemotherapy are potentially good options for developing CRC treatment regimens. In this study, sertraline, an antidepressant drug, and paclitaxel, an anticancer drug, were chosen to study their antitumor effects in the treatment of colorectal cancer, alone or in combination, and to explore their underlying mechanisms. The data showed that sertraline exerted a dose-dependent cytotoxic effect on MC38 and CT26 colorectal cancer cell lines with IC50values of 10.53 μM and 7.47 μM, respectively. Furthermore, sertraline synergistically sensitized chemotherapeutic agent paclitaxel efficacy in CRC cells with combination index (CI) values at various concentrations consistently lower than 1. Sertraline remarkably augmented paclitaxel-induced autophagy by increasing autophagosome formation indicated by elevated LC3-II/I ratio and promoting autophagic flux by degrading autophagy cargo receptor SQSTM1/p62, which may explain the synergistically cytotoxic effect of sertraline and paclitaxel combination therapy on CRC cells. This study provides important evidence to support repurposing sertraline as an anticancer agent and suggests a novel combinational regimen for effectively treating CRC as well as in the simultaneous treatment of CRC and depression.
研究领域:
肿瘤学
·
药理学
·
癌症生物学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
·
2025
·
IF 5.4
Yang Yu,Lixin Fan,Chunling Gao,Yang Ping,Liting Mu,Weitong Sun
Despite the advances made in cancer treatment, malignant tumors remain a significant threat to human health. Tumor multidrug resistance (MDR) constitutes a significant impediment to the effectiveness of chemotherapy. Thus, the reversal of MDR has become a critical research domain for medical professionals. Now, paclitaxel (PTX) is encapsulated in a reduction-sensitive polymer pre-drug micelle called mPEG-SS-IND(PSI), which reduces the MDR of PTX and enhances its anti-tumor efficacy. The PSI/PTX micelles show excellent reduction sensitivity and stability. In vitro , the harmful effect of PTX on MCF-7/PTX cells is enhanced by the PSI/PTX micelles, while its damaging effect on normal cells is decreased. Furthermore, compared to PTX solution, PTX encapsulated in PSI/PTX micelles exhibits reduced volume distribution and clearance, longer blood circulation time, and greater drug concentration area under the curve. Furthermore, in vivo studies using BALB/c subcutaneous tumor-bearing mice demonstrate decreased systemic toxicity and enhanced therapeutic effectiveness of PTX. This study proves that the potential utility of reduction-sensitive polymer pre-drug micelles as a delivery method for overcoming MDR for PTX and targeting tumors.
研究领域:
药理学
·
肿瘤学
·
药物递送系统
·
癌症治疗
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
You Li,Wei Liu,Ying Li,Tao Peng,Jing Wang,Tao Zou
Human serum albumin (HSA)-indocyanine green (ICG)-paclitaxel (PTX) nanoparticles have been prepared for tumor photothermal-photodynamic-chemotherapy, which was inevitably internalized by normal cells. Here, hyaluronic acid (HA)-HSA-ICG-PTX nanoparticles were designed for active targeting mediated tumor multimodal therapy. HA as a ligand imparted the characteristics of the nanoparticles to specifically target the CD44 receptors overexpressed tumor cells, while enhancing the stability of the nanoparticles. HSA-ICG-PTX@HA nanoparticles were selectively internalized by CD44 overexpressed cervical and breast cancer (Hela and MCF-7) cells, rather than normal (293) cells lacking the receptor. Moreover, compared with HSA-ICG-PTX nanoparticles, HSA-ICG-PTX@HA nanoparticles exhibited improved tumor cell uptake and cytotoxicity, as well as enhanced photothermal effects and tumor suppressor effects. Therefore, tumor-targeting, human serum protein-based nanoparticles entirely consisting of FDA-approved compounds were demonstrated for fluorescent-photoacoustic-photothermal imaging mediated multimodal tumor therapy.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF POLYMER SCIENCE
·
2024
·
IF 3.9
Na Liang,Caixia Yan,Zhenrong Liu,Wenlong Hu,Kun Jiang,Gang Li,Shaoping Sun
To improve the therapeutic efficiency of paclitaxel (PTX) and reduce its toxicity to normal tissues, a novel hydroxypropyl-β-cyclodextrin (HP-β-CD) derivative has been designed and developed. The polymer (bio-HP-β-CD(NAC)-PLA) is synthesized by modifying HP-β-CD with polylactic acid, cysteine, and biotin. Using bio-HP-β-CD(NAC)-PLA as the carrier, a PTX-loaded nanoparticulate system is developed by a modified emulsion solvent evaporation method. The optimized drug-loaded nanoparticles are obtained with a mean diameter of 162.4 nm and drug loading of 16.1%. In vitro drug release study exhibits that PTX is released in a redox-dependent manner. Cellular uptake study suggests that the bio-HP-β-CD(NAC)-PLA nanoparticles can be specifically taken up by MCF-7 cells via the biotin receptor-mediated endocytosis. In vitro and in vivo anticancer efficacy evaluations demonstrate the superior antitumor activity and negligible toxicity of the PTX-loaded nanoparticles. It can be concluded that the proposed polymer bio-HP-β-CD(NAC)-PLA offers a promising drug delivery system for targeted delivery and controlled release of PTX. Graphical
研究领域:
药学
·
肿瘤学
·
纳米医学
✓ 已验证
产品关联
DOI
高影响因子
MATERIALS & DESIGN
·
2024
·
IF 7.6
Ying Liu,Shengxue Yu,Xue Jiang,Qian Wu,Wenwen Shen,Zhiru Zou,Wei Wei,Chao Wu,Yu Gao
Brain glioma is a highly comorbid tumor with high mortality. In this study, plasma complex component-functionalized manganese-doped mesoporous silica nanoparticles (PMMSN) were prepared and loaded with paclitaxel (PTX) by adsorption for brain glioma treatment. The nanodrug delivery system crossed the blood–brain barrier (BBB) and exhibited redox responsiveness and pH-sensitive release characteristics. In vivo imaging revealed the ability of the preparation to cross the BBB, and oxidative stress studies revealed the redox properties of the carrier material. The drug release data indicated that the amount of drug released from the drug-loaded samples (PMMSN-PTX) in medium at pH 5.0 was 84.1 ± 1.62 % after 10 h, whereas it was 53.7 ± 1.53 % in pH 7.4 medium after 24 h. These findings demonstrated that the drug was pH sensitive and released slowly. In vitro cell-based assays, including cellular uptake, flow cytometry, western blotting, and immunofluorescence staining, showed that PMMSN-PTX facilitated drug delivery across the BBB and promoted tumor cell apoptosis. These in vivo antitumor effects further demonstrated that it significantly inhibited tumor cell proliferation. We believe that PMMSN-PTX is a promising bionic nanosystem agent that could be used as a new agent for treating glioma.
研究领域:
纳米技术
·
药学
·
神经肿瘤学
·
药物递送系统
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION
·
2020
·
IF 2.69
Bo Li,Shigang Pang,Xinxin Li,Yanhai Li
Here we demonstrate a type of pH and redox dual-responsive micelles, which were self-assembled in aqueous solution by an amphiphilic polymer, methoxypoly(ethylene glycol)-cystamine-poly(L-glutamic acid)-imidazole (mPEG-SS-PGA-IM). Considering tumor cells or tissues exhibiting low pH values and high glutathione (GSH) concentration, mPEG-SS-PGA-IM micelles possessed the charge conversion at pH of tumor tissues, which can facilitate cellular uptake of tumor cells. Furthermore, mPEG-SS-PGA-IM micelles can escape from endo/lysosomes based on the proton sponge effect, following degraded by higher concentration of GSH in cytoplasm. CLSM images of HCT116 cells indicated that mPEG-SS-PGA-IM micelles can escape from endo/lysosomes and enter cytoplasm. MTT assay showed that (paclitaxel) PTX-loaded mPEG-SS-PGA-IM micelles had higher cytotoxicity against HCT116 cells compared with PTX-loaded mPEG-PBLG and mPEG-SS-PBLG micelles. These results indicated that these mPEG-SS-PGA-IM micelles, as novel and effective pH- and redox-responsive nanocarriers, have great potential to both improve drug targeting efficiency while also enhancing the antitumor efficacy of PTX.
研究领域:
药剂学
·
肿瘤学
✓ 已验证
DOI
高影响因子
Journal of Biomedical Nanotechnology
·
2019
·Vol. 15
·期 7
·1532-1545
·
IF 0
Wang Xiaoxiao,Wang Jinmei,Feng Sishen,Zhang Zhian,Wu Chao,Zhang Xuxu,Kang Feiyu
Not only dose oral administration have the highest safety, convenience and patient compliance, but also can improve patients' quality of life and reduce health care costs in many cases when compared to the parenteral route. However, many drugs, especially most anticancer drugs such
as paclitaxel (PTX), are not orally bioavailable, which is attributed to low aqueous solubility, poor intestinal permeability, and the high level of P-glycoprotein (P-gp) efflux. In this study, we developed a nano-porous silica aerogel delivery system for oral administration of PTX that improved
the bioavailability, reduced the side effects of the drug and inhibited tumor growth. The advantages of nano-porous silica aerogel include very high porosities, vast specific surface areas, high drug-loading rate, high biological safety, excellent biocompatibility, and biological inertia,
which can also be applied to a variety of drugs. The aerogel delivery system is a universal pharmaceutical system that has huge potential in the field of pharmacy.
研究领域:
药学
·
肿瘤学
·
材料科学
✓ 已验证
DOI
PubMed
DRUG DELIVERY
·
2017
·
IF 6.402
Jian Hou,E. Sun,Zhen-Hai Zhang,Jing Wang,Lei Yang,Li Cui,Zhong-Cheng Ke,Xiao-Bin Tan,Xiao-Bin Jia,Huixia Lv
The aim of this study was to establish a paclitaxel (PTX)-loaded mixed micelle delivery system (PTX-TP-M) with vitamin E-TPGS (TPGS) and Plasdone®S-630 Copovidone (PVPS630) as carriers to improve the solubility, oral absorption, and anti-tumor activity of PTX against lung cancer. In this study, PTX-TP-M was prepared using the ethanol thin-film dispersion method followed by characterization of the binary mixed micelles system. The average size of the PTX-TP-M was 83.5 ± 1.8 nm with a polydispersity index of 0.265 ± 0.007 and the drug loading (DL%) and entrapment efficiency (EE%) were 3.09 ± 0.09% and 95.67 ± 2.84%, respectively, which contributed to a high solubility of PTX about 24947-fold increase in water (4.78 ± 0.14 mg/mL). In addition, TEM analysis showed that the PTX-TP-M appeared spherical in structure and was well dispersed without aggregation and adhesion. In vitro release studies showed that the PTX-TP-M displayed a sustained release compared to free PTX in the dialysis bag. The efflux ratio of PTX reduced from 44.83 to 3.52 when formulated as PTX-TP-M; a 92.15% reduction, studied using the Caco-2 monolayer model. The oral bioavailability of PTX also improved by 4.35-fold, suggesting that PTX-TP-M can markedly promote the absorption in the gastrointestinal tract. Using in vitro MTT assays, it was observed that cytotoxicity was markedly increased, and IC50 values of PTX-TP-M (3.14 ± 0.85 and 8.28 ± 1.02 μg/mL) were lower than those of PTX solution (5.21 ± 0.93 and 14.53 ± 1.96 μg/mL) in A549 and Lewis cell, respectively. In vivo anti-tumor studies showed that PTX-TP-M achieved higher anti-tumor efficacy compared with PTX in Lewis bared C57BL/6 mice. Furthermore, a gastrointestinal safety assay also proved the safety of PTX-TP-M. All results demonstrated that the PTX-TP-M exhibited great potential for delivering PTX with increased solubility, oral bioavailability, and anti-cancer activity and this binary mixed micelles drug delivery system has potential to be used clinically.
研究领域:
药学
·
肿瘤学
·
药物递送系统
·
药代动力学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）