Journal of Biomedical Nanotechnology
·
2020
·Vol. 16
·期 7
·1160-1168
·
IF 4.483
Liu Qiaoming,Cheng Meng,Liang Jianqin,Jin Yi,Feng Jianfang,Tu Liangxing
The oral administration of paclitaxel suffering obstacles like poorly solubility and low permeability, causing extremely low oral bioavailability. In this study, we aim to study the role of transmembrane pathway on the absorption mechanisms of PTX-Micelles. In addition, we will further
study the permeability of PTX-Micelles by employing in situ perfusion model. The results showed the PTX-Micelles could be up taken by caco-2 intact. In addition, we found that the endocytosis pathway and M cells pathway attended, while paracellular pathway absented in the transport
process of PTX-Micelles. The study on in situ perfusion showed the absorption rate constant (Ka) of PTX was enhanced from 6.3, 6.1, 10.6 and 13.6 × 10–2/min to 15.1, 18.4, 45.6 and 42.9 × 10–2/min by micelles in duodenum, jejunum, ileum
and colon, respectively, indicating the PTX-Micelles could enhance the permeability of PTX in intestinal membrane. This study indicating that transmembrane pathway-mediated transport is an important part in the transport process of polymeric micelles, and designing formulation based on transmembrane
pathways may be a promising route for oral bioavailability enhancement of poor-soluble drugs.
研究领域:
药学
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药理学
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药物递送系统
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生物药剂学
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DOI
PubMed
高影响因子
ANNALS OF CLINICAL AND LABORATORY SCIENCE
·
2023
·Vol. 53
·期 1
·116-125
·
IF 0.8
Yunfang Cai,Ting Zhang,Guiying Chen,Chunxi Liu
Objective Flap endonuclease 1 (FEN1) has been confirmed to involve the drug resistance of multiple cancers including breast cancer.However, the effect of miRNA-mediated FEN1 on breast cancer cell resistance is still ambiguous and needs further research. Methods Firstly, we used GEPIA2 to predict the FEN1 expression in breast cancer. Next, we used quantitative real-time polymerasechain reaction (qRT-PCR) and western blot to evaluate the FEN1 level of cells. After parental cells or MDA-MB-231-paclitaxel(PTX) cells being transfected with or without siFEN1, the apoptosis, migration, and protein levels of FEN1, Bcl-2, and resistance-relatedgenes were examined by flow cytometry, wound healing assay, and western blot, respectively. Then, the putative miRNA targetingFEN1 was predicted using StarBase V3.0, and further confirmed by qRT-PCR. The targeted binding of FEN1 to miR-26a-5p was detectedby dual-luciferase reporter assay. After parental cells or MDA-MB-231-PTX cells being transfected with or without miR-26a-5pmimic, the apoptosis, migration, and protein levels of FEN1, Bcl-2, and resistance-related genes were tested again. Results FEN1 expression was enhanced in breast cancer and MDA-MB-231-PTX cells. The combined application of FEN1 knockdown and PTXenhanced apoptosis in MDA-MB-231-PTX cells but suppressed cell migration and expressions of FEN1, Bcl-2, and resistance-relatedgenes. Then, we confirmed that FEN1 was targeted by miR-26a-5p. The combined application of miR-26a-5p mimic and PTX largelyfacilitated apoptosis in MDA-MB-231-PTX cells but restrained cell migration and expressions of FEN1, Bcl-2, and resistance-relatedgenes. Conclusion MiR-26a-5p contributes to the sensitivity of breast cancer cells to paclitaxel via restraining FEN1.
研究领域:
肿瘤学
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分子生物学
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药理学
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DOI
PubMed
高影响因子
CHINESE JOURNAL OF CHEMICAL ENGINEERING
·
2026
·
IF 3.5
Minghong Feng,Teng He,Haiqian Zhao,Tao Chen,Wenjing Lin,Chufen Yang
To address the challenges of poor stability and weak targeting capability in polymeric micelles, which negatively impact controlled drug release performance, pH-responsive polymers PCL-PDEAEMA-PHEMA-PPEGMA (P1, P2, and P3) with distinct block lengths were designed and synthesized in this work. These copolymers were rigorously characterized using 1 H NMR, FT-IR, and GPC. Subsequently, polymer P3 was selected for modification based on comparative analyses of critical micelle concentrations (CMC) and drug-loading performance. Polymer P3 underwent esterification with lipoic acid (LA) and folic acid (FA) to yield LA-P3 and FA-P3, respectively. These derivatives were blended at a mass ratio of 1:1 (LA-P3:FA-P3), and dithiothreitol was employed to initiate self-crosslinking, resulting in the preparation of actively targeted crosslinked mixed micelles (C-MIX). The results revealed that C-MIX@PTX drug-loaded micelles prepared at a feeding ratio of 15 mg PTX/30 mg polymer exhibited a smaller size (134.7 nm) compared to non-crosslinked micelles, with a drug-loading content of 15.31 ± 1.79% and an encapsulation efficiency of 38.42 ± 5.22%. In vitro release studies demonstrated that under neutral conditions, C-MIX@PTX achieved a cumulative drug release of 16.8% at 120 h, significantly lower than non-crosslinked micelles. Under acidic/reductive conditions, C-MIX@PTX showed a cumulative drug release of 77.1% at 120 h, slightly lower compared to non-crosslinked micelles. Cytotoxicity assays confirmed that both MIX and C-MIX were biocompatible low-toxicity carrier materials, while LA-P3@PTX, FA-P3@PTX, MIX@PTX, and C-MIX@PTX exhibited inhibitory effects on HepG2 cells, FA-P3@PTX with folate-modified demonstrated enhanced efficacy.
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产品关联
DOI
高影响因子
Nano Today
·
2026
·
IF 10.7
Lele Zhang,Huimin Zhang,Mao-Hua Zhu,Yanhu Huang,Xin Wen,Jiayan Lyu,Wenxi Mo,Jiangpei Shi,Qin Lu,Peng Sun,Jonathan F. Lovell,Hong-Zhuan Chen,Zeli Yuan,Xing Lai,Chao Fang
Liposomes are among the most potent drug delivery nanocarriers in clinical translation, yet the encapsulation of hydrophobic agents within the phospholipid bilayer often possesses limited stability, resulting in accelerated drug leakage and compromised therapeutic efficacy. Here, we report that nanobowl-supported liposomes (NbLipo) can overcome limitations associated with bilayer-loaded drug delivery. The nanobowl embedded within the aqueous cavity of NbLipo resulted in improved encapsulation and loading stability of paclitaxel (PTX), a model hydrophobic drug, with concomitant decreased phospholipid bilayer fluidity and enhanced membrane stability. Proteomic analysis further revealed that nanobowl-supported bilayers reduced serum protein adsorption and modulated the components of the protein corona, characterized by enrichment of CD55 (a complement inhibitor) and downregulation of complements C3 and C5. These effects decreased serum protein-induced drug leakage and complement-mediated blood clearance, leading to superior antitumor efficacy in cytotoxicity and orthotopic 4T1 tumor bearing mice compared with conventional liposomes. This work shows that nanobowl-supported bilayer approaches can improve membrane stability and expand therapeutic potential of liposomal formulations for hydrophobic drugs.
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产品关联
DOI
高影响因子
RSC Advances
·
2020
·Vol. 10
·期 46
·27676-27687
·
IF 3.119
Jiang Yu,Shuang Zhou,Jinbo Li,Yingli Wang,Yujiao Su,Dongxu Chi,Jiamei Wang,Xue Wang,Zhonggui He,Guimei Lin,Dan Liu,Yongjun Wang
Liposomes are among the most successful nanocarriers; several products have been marketed, all of which were prepared by active loading methods. However, poorly water-soluble drugs without ionizable groups are usually incorporated into the lipid bi-layer of liposomes by passive loading methods, with serious drug leakage during blood circulation. Furthermore, there have been few improvements in their anti-cancer activity and safety. Herein, we designed and synthesized three weak-acid modified paclitaxel (PTX) derivatives with a one-step reaction for the remote loading of liposomal formulations. By comparison, PTX-succinic acid liposomes (PTX-SA LPs) exhibited the highest encapsulation efficiency (97.2 ± 1.8%) and drug loading (8.84 ± 0.16%); meanwhile, there was almost no change in their particle size or zeta potential within one month. Furthermore, compared with Taxol®, the PTX-SA LPs showed a 4.35-fold prolonged half-time, enhanced tumor accumulation, and an increased maximum tolerated dose (MTD) of more than 30 mg kg−1. As a result, the PTX-SA LPs displayed significantly improved in vivo anti-cancer efficacy in comparison with Taxol®. Therefore, weak-acid modification is proved to be a simple and effective method to achieve remote loading and high encapsulation efficiency of poorly soluble drugs, showing great potential for clinical application.
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
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2020
·
IF 4.389
Mengyao Liu,Manfei Fu,Xiaoye Yang,Guoyong Jia,Xiaoqun Shi,Jianbo Ji,Xianghong Liu,Guangxi Zhai
Multidrug resistance (MDR) in tumor has long been considered a major factor in the failure of tumor chemotherapy. P-glycoprotein (P-gp)-mediated drug efflux plays a significant role in the MDR of tumor. Herein, paclitaxel (PTX) and P-gp inhibitor quercetin (QC) co-loaded and chondroitin sulfate (ChS)-coated mesoporous silica nanoparticles (MSNs) ( [email protected] ) were developed to reverse MDR in breast cancer and improve chemotherapy efficacy. The dual drug-loaded nanoparticles (NPs) showed a nanoscale size of ∼ 227.2 nm and redox-responsive drug release property. In vitro cell experiments showed that NPs exhibited CD44 receptor-mediated active targeting in MCF-7/ADR cells. The dual drug-loaded NPs had lower IC 50 value, higher apoptosis rate, obvious G2M phase arrest as well as stronger microtubule destruction in MCF-7/ADR cells compared to PTX-loaded NPs, suggesting that QC addition, significantly, improved the sensitivity of MCF-7/ADR cells to PTX. Further study found that QC-loaded NPs down-regulated the expression of P-gp. Notably, the dual drug-loaded NPs exhibited tumor-targeting ability, prolonged tumor retention time and effective anti-tumor effect without obvious toxicity to normal tissues in vivo . Taken together, our research provides a viable approach to overcome MDR in breast cancer.
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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生物医学工程
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产品关联
DOI
PubMed
高影响因子
DRUG DELIVERY
·
2020
·
IF 4.902
Tan Yang,Jianfang Feng,Qian Zhang,Wei Wu,Hailan Mo,Lanzhen Huang,Wei Zhang
A delivery system based on l-carnitine (LC) conjugated chitosan (CS)-stearic acid polymeric micelles has been developed for improving the oral bioavailability of paclitaxel (PTX) through targeting intestinal organic cation/carnitine transporter 2 (OCTN2). Stearic acid grafted chitosan (CS-SA), as micelle skeleton material, was synthesized by 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC)-mediated coupling reaction. The PTX-loaded micelles were prepared by solvent evaporation-hydration method, and the ligand LC was conjugated onto the micelle surface by anchoring its derivative stearoyl group to the lipophilic core of micelle. The modified polymeric micelles showed regular spherical shapes with small particle size of 157.1 ± 5.2 nm and high drug loading capacity of 15.96 ± 0.20 wt%, and the micelle stability in water was supported by low critical micelle concentration of 14.31 ± 0.21 μg/ml. The drug-loaded micelles presented a slow and incomplete in vitro release, and the pharmacokinetic studies indicated the micelle carriers increased the relative bioavailability of PTX to 165.8% against the commercial formulation. The enhancement effect on intestinal absorption was also confirmed by the intracellular uptake of Caco-2 cells. The proposed micelle carrier system manifested a prospective tool for oral drug delivery.
研究领域:
药剂学
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药物递送系统
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分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2015
·Vol. 13
·期 1
·1-11
·
IF 4.115
Wang Bing,Yu Xiu-Chun,Xu Song-Feng,Xu Ming
Background The combination of chemotherapeutic drugs with different pharmacological action has emerged as a promising therapeutic strategy in the treatment of cancers. Present study examines the antitumor potential of paclitaxel (PTX) and etoposide (ETP)-loaded PLGA nanoparticles for the treatment of osteosarcoma.Results The resulting drug-loaded PLGA NP exhibited a nanosize dimension with uniform spherical morphology. The NP exhibited a sustained release profile for both PTX and ETP throughout the study period without any sign of initial burst release. The combinational drug-loaded PLGA NP enhanced the cytotoxic effect in MG63 and Saos-2 osteosarcoma cell lines, in comparison to either native drug alone or in cocktail combinations. Additionally, NPs showed an appreciable uptake in MG63 cells in a time-based manner. Co-delivery of anticancer drugs resulted in enhanced cell cycle arrest and cell apoptosis. The results clearly showed that combinational drugs remarkably improved the therapeutic index of chemotherapeutic drugs. The greater inhibitory effect of nanoparticle combination would be of great advantage during systemic cancer therapy.Conclusion Taken together, our study demonstrated that PTX-ETP/PLGA NP based combination therapy holds significant potential towards the treatment of osteosarcoma.
研究领域:
肿瘤学
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药学
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纳米技术
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2021
·
IF 6.953
Jingsong Cao,Xiaodan Wu,Litao Wang,Guansong Shao,Bingyang Qin,Zihan Wang,Tao Wang,Yujie Fu
A microcrystalline cellulose-based temperature sensitivity paclitaxel molecular imprinted hydrogel (MCC-TSMIHs-PTX) was successfully prepared by temperature-sensitive monomer N-isopropylacrylamide, functional monomer 4-vinylpyridine, cross-linking agent N , N ′-methylenebisacrylamide and microcrystalline cellulose . They showed imprinting effective responses to the temperature changes. The results of adsorption kinetics , adsorption equilibrium, thermodynamics, selectivity and reusability showed the successful formation of a grafting thermosensitivity hydrogel with higher adsorption capacity and specific recognition. When the temperature reached 308 K, imprinting effect of hydrogel cavities would be most effective and conducive to capture template molecules. When the temperature reached 288 K, the lowest imprinting effect would facilitate the desorption of PTX. Finally, the MCC-TSMIHs-PTX was applied to enrich the paclitaxel in Taxus × media extracts samples, the relative contents of PTX in the samples were increased greatly from 7.23% to 78.32%, indicating the MCC-TSMIHs-PTX was a stable adsorption capacity for efficient separation and enrichment of PTX in Taxus × media extracts.
研究领域:
材料科学
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药物化学
·
生物技术
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产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2018
·
IF 3.997
Min Yang,Houqiang Ding,Yixin Zhu,Yanxiu Ge,Lingbing Li
A strategy of preparing mixed micelles containing both DOX prodrug and PTX prodrug was developed, i.e., synthesizing a DOX conjugate and a PTX conjugate started with the same biocompatible amphiphilic copolymer, TPGS and DTDPA, a linker containing disulfide bond. The mixed micelles were prepared by co-assembling the two conjugates with a particle size about 98.5 nm. The mixed micelles could release anticancer drug DOX and PTX upon cellular reduction once they came into the cancerous cells. Moreover, the mixed micelles displayed synergistic effect in vitro and the combination therapy in micellar dosage-form led to reduced systematic toxicity and enhanced antitumor efficacy in vivo .
研究领域:
药剂学
·
肿瘤学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2016
·
IF 3.782
Tingting Zhao,Xin Liu,Yuebin Li,Mingguang Zhang,Jian He,Xuewen Zhang,Hui Liu,Xingguo Wang,Haoshuang Gu
Hydrophobic ZnSe:Mn/ZnS core-shell fluorescence quantum dots (QDs) and anticancer drug paclitaxel (PTX) have been co-loaded into folate conjugated hybrid silica nanocapsules via F127 micelles based soft-template method in a mild aqueous environment at room temperature . The encapsulation of QDs shows a F127: QDs mass ratio dependent behavior, which impact much on the morphology and optical properties of composite nanocapsules . These as prepared composite nanocapsules also exhibit good photoluminescence stability under the temperature ranges from 19 °C to 49 °C. In addition, the aqueous solubility of PTX (0.1 μg/mL) can be efficiently enhanced about 630 times to 62.99 μg/mL, and the loaded PTX could be released during 12 h sustainably. These tunable fluorescence, enhanced drug loading efficiency and sustained release behavior manifest that the hybrid nanocapsule is a promising theranostic nanoplatform for future combined fluorescence imaging and chemotherapy.
研究领域:
生物医学工程
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纳米医学
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药剂学
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产品关联
DOI
PubMed
高影响因子
TALANTA
·
2016
·
IF 4.035
Yuling Chen,Zilin Chen
Novel covalent organic framework-1 modified magnetic nanoparticles (M-COF-1) were prepared for extraction of paclitaxel from rat plasma samples. Paclitaxel is an important anti-cancer drug in clinical chemotherapy. COF-1 was immobilized on the surface of magnetic nanoparticles by bio-inspired polydopamine functionalization method because polydopamine can supply catechol groups for supporting the immobilization of COF-1. The formation of M-COF-1 has been confirmed by Fourier transform infrared spectroscopy and transmission electron microscopy . A M-COF-1-based extraction method was developed for selective extraction of paclitaxel in aqueous solutions. Extraction conditions were investigated, including sample pH value, acetonitrile content, extraction time and sample volume. By combining with HPLC, this method showed a good linear range of 0.1–200 ng/mL with a low limit of detection of 0.02 ng/mL. The method was also applied for the pretreatment of paclitaxel in rat plasma samples, which showed effective enrichment efficiency and good clean-up capacity. Recoveries were calculated to be 99.4–103.7% with relative standard deviations less than 2.3%.
研究领域:
药物分析
·
纳米技术
·
临床医学
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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）