MOLECULAR PHARMACEUTICS
·
2024
·
IF 4.5
Yue Wang,Ping Wang,Haiyan Li,Xiaoran Han,Haibin Zhu,Xiangqun Jin
To improve the oral absorption and anticancer efficacy of the BCS-IV drug etoposide (ETO), oral nanocrystal-loaded lipid carriers (Lipo@NCs) were developed in this study by modifying the BCS-IV drug nanocrystal with the lipid bilayer. The ETO-Lipo@NCs were prepared by the thin film hydration high-pressure homogenization method, and the core of positively charged ETO nanocrystals was prepared by the sonoprecipitation-high pressure homogenization method. The optimized ETO-Lipo@NCs were spherical particles with an average particle size of 220.3 ± 14.2 nm and a zeta potential of −9.95 ± 0.81 mV, respectively. The successful coating of a lipid bilayer on the surface of nanocrystals in ETO-Lipo@NCs was confirmed by several characterization methods. Compared to nanocrystals, the release rate and degree of Lipo@NCs in SIF were significantly decreased, indicating that the lipid bilayer can effectively prevent the rapid dissolution of core nanocrystals. ETO-Lipo@NCs demonstrated a significant improvement in the intestinal permeability and absorption of ETO in a single intestinal perfusion experiment. In the cells, ETO-Lipo@NCs showed enhanced cellular uptake and transepithelial transport compared with ETO nanocrystals. Pharmacokinetic analysis indicated that ETO-Lipo@NCs had a longer plasma half-life than ETO solution, and the oral bioavailability of ETO-Lipo@NCs was 1.96- and 10.92-fold higher than that of ETO nanocrystals and ETO coarse crystals, respectively. Moreover, the ETO-Lipo@NCs orally dosed at 10 mg/kg exhibited an excellent inhibitory effect against tumors in a subcutaneous Lewis lung carcinoma (LLC) xenograft model compared with other preparations. These results indicate that the Lipo@NCs formulation has an oral absorption-promoting effect of the BCS-IV drug ETO, which could warrant further application in the oral delivery of other poorly bioavailable drugs.
研究领域:
药剂学
·
肿瘤学
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMEDICAL CHROMATOGRAPHY
·
2018
·Vol. 32
·期 6
·e4192
·
IF 1.688
Dan Li,Gang Zhao,Weipeng Ai,Gao Li,Luqin Si,Jiangeng Huang,Yunzhou Chen,Sanlan Wu
In this study, a liquid chromatography–tandem mass spectrometry (LC-MS/MS) method was developed and validated to simultaneously determine the anticancer drugs etoposide and paclitaxel in mouse plasma and tissues including liver, kidney, lung, heart, spleen and brain. The analytes were extracted from the matrices of interest by liquid–liquid extraction using methyl tert -butyl ether–dichloromethane (1:1, v/v). Chromatographic separation was achieved on an Ultimate XB-C 18 column (100 × 2.1 mm, 3 μm) at 40°C and the total run time was 4 min under a gradient elution. Ionization was conducted using electrospray ionization in the positive mode. Stable isotope etoposide-d3 and docetaxel were used as the internal standards. The lower limit of quantitation (LLOQ) of etoposide was 1 ng/g tissue for all tissues and 0.5 ng/mL for plasma. The LLOQ of paclitaxel was 0.4 ng/g tissue and 0.2 ng/mL for all tissues and plasma, respectively. The coefficients of correlation for all of the analytes in the tissues and plasma were >0.99. Both intra- and inter-day accuracy and precision were satisfactory. This method was successfully applied to measure plasma and tissue drug concentrations in mice treated with etoposide and paclitaxel-loaded self-microemulsifying drug-delivery systems.
研究领域:
药物分析
·
肿瘤学
·
药代动力学
✓ 已验证
DOI
PubMed
高影响因子
ChemistrySelect
·
2024
·Vol. 9
·期 48
·e202404117
·
IF 1.9
Subbulakshmi Ganesan,Vijay J. Upadhye,Nutan Sharma,Arpit Arora,Arunachalam Chinnathambi,Sulaiman Ali Alharbi,Samer Hasan Hussein-Al-Ali,Suha Mujahed Abudoleh,Indumathi Thangavelu
Graphical Liver cancer is the most important global health problem. The development of new anticancer drugs for its treatment is a challenge. Herein, we present a sorafenib tosylate (ST) and etoposide (ETP) encapsulated liposomes for precision liver cancer therapy and its apoptosis induction. Nanotechnology is an effective tool in fighting against cancer, playing a crucial role in investigating and fabricating novel anticancer drugs. Recognizing the worldwide prevalence of cancer, we combined sorafenib tosylate (ST) and etoposide (ETP) within liposomes. We assessed their ability to kill human umbilical vein endothelial cells (HUVECs) and HepG2 liver cancer cells. The liposomes effectively contained ST and ETP, exhibiting a particle size distribution below 180 nm, a polydisperse index (PDI) below 0.2, a spherical shape, a strong negatively charged zeta potential, and encapsulation efficiencies of 59% for ST, 88% for ETP, and 57% for ST combined with 87% for ETP. The FTIR analysis indicates that the drugs were incorporated within liposomes. Encapsulation of the drugs in liposomes resulted in a more significant cytotoxic impact on HepG2 cells and a reduced cytotoxic impact on HUVECs. The morphological assessment of the HepG2 liver cancer cells was investigated using AO-EB and Hoechst 33258 staining methods. Apoptosis mechanisms of HepG2 cells were examined by Annexin V and PI dual staining. Furthermore, the coadministration of ST and ETP, which were enclosed in liposomes, resulted in a synergistic impact on the drugs, leading to cell death by apoptosis.
研究领域:
药学
·
肿瘤学
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
Oncotarget
·
2016
·
IF 5.008
Lian Chen,Hengmin Cui,Jing Fang,Huidan Deng,Ping Kuang,Hongrui Guo,Xun Wang,Ling Zhao
Glutamine provides cancer cells with the energy required to synthesize macromolecules. Methods which block glutamine metabolism in treatment of breast cancer inhibit oncogenic transformation and tumor growth. We investigated whether inhibiting glutamine metabolism produces effects that are synergistic with those produced by drugs which damage DNA in triple-negative breast cancer cells. HCC1937 and BT-549 breast cancer cells were co-treated with either cisplatin or etoposide in combination with BPTES (a specific inhibitor of glutaminase 1) or exposure to a glutamine-free medium, and the cell proliferation and cell apoptosis were measured by flow cytometry, immunoblotting studies, and CCK-8 assays. The results showed that both glutamine deprivation and BPTES pretreatments increased the toxic effects of cisplatin and etoposide on HCC1937 cells, as demonstrated by their reduced proliferation, increased expression of apoptosis-related proteins (cleaved-PARP, cleaved-caspase 9, and cleaved-caspase 3) and decreased Bcl-2/BAX ratio. However, in BT-549 cells, glutamine deprivation and BPTES treatment increased etoposide-induced apoptosis only when used with higher concentrations of etoposide, and the effect on cisplatin-induced apoptosis was minimal. These results suggest that the anti-cancer effects produced by a combined approach of inhibiting glutamine metabolism and administering common chemotherapeutic agents correlate with the tumor cell type and specific drugs being administered.
研究领域:
肿瘤学
·
药理学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PROCESS BIOCHEMISTRY
·
2023
·
IF 4.4
Zhihua Wang,Ye Wang,Hailiang Li,Yuanxiang Lan,Zhong Zeng,Jian Yao,Mei Li,Hechun Xia
Recent research has shown that etoposide (ETP), an immunomodulatory medication, can have cytotoxic effects. When accompanied by nano-drug delivery, this possibility can lead to a more effective treatment for cancer. This study involved the delivery of ETP via PDA@SPIONs (termed as ETP-PDA@SPIONs), which are superparamagnetic iron oxide nanoparticles (SPIONs) that have been coated with polydopamine (PDA) and utilized to treat C6 and U87 glioma cancer cell lines. The particle diameter, polydispersive index (PDI), zeta potential , and shape of nanoparticles were determined. The fabricated nanoparticles had a mean particle size of 164 ± 7 nm and a − 37 ± 3 mv zeta potential. Cell lines were tested for sensitivity to PDA@SPIONs, free-ETP, and ETP-PDA@SPIONs. On the cell lines, we tested the proliferation of PDA@SPIONs, free-ETP, and PDA@SPIONs loaded with ETP. The cytotoxicity of ETP-PDA@SPIONs was substantially higher than that of free-ETP-treated cells. The cells' morphological changes were examined by dual staining (acridine orange/ethidium bromide, AO/EB) and nuclear staining methods. Interestingly, this inhibitory impact was not ascribed to the known cellular membrane destruction, cell membrane damage, and reactive oxygen species (ROS). Further tests demonstrated that the nanoparticles substantially impacted mitochondrial functioning, resulting in an aberrant mitochondrial shape, and reduced mitochondrial membrane potential (MMP). Future studies into glioma cancer therapy may want to investigate using the proposed ETP-loaded nanoparticles.
研究领域:
肿瘤学
·
纳米医学
·
药理学
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2015
·
IF 3.65
Lijuan Chen,Liwei Tan,Xiaoning Zhang,Jun Li,Zhiyong Qian,Mingli Xiang,Yuquan Wei
In this paper, we systemly compared the two kinds of VP16 (etoposide) loaded polymers micelles , monomethyl poly (ethylene glycol)-poly (lactic acid) (MPEG-PDLLA) and monomethyl poly (ethylene glycol)-poly (ϵ-caprolactone) (MPEG-PCL) in vitro and in vivo . Molecular modeling study was used as a novel means to compare the two formulations. In vitro , the micelle samples were fully characterized by TEM, XRD, drug loading (DL), Encapsulation efficiency (EE), stability and MTT. The stability study revealed that MPEG-PDLLA-VP16 had the significant advantage of 100% drug retention within 48 h compared to MPEG-PCL-VP16 with 40%, conform to the computer simulation model results. Cellular uptake figured that MPEG-PDLLA-VP16 had a 7 times larger uptake rate in the H460 cell line. In vivo , pharmacodynamics results showed MPEG-PDLLA-VP16 perform no significant difference with VP16 clinical formulations (10, 20 mg/kg). However, MPEG-PCL-VP16 had no difference between different dosages on anticancer activities. Plasma pharmacokinetics results showed that the two micelle formulations prolong the half-life of VP16 twice than that of VP16 clinical formulations. In conclusion, micelle were better choice for cancer treatment on reducing drug toxic. In this study, the results also indicated that MPEG-PDLLA was more suitable for VP16 than MPEG-PCL as a more promising formulation for clinical cancer treatment.
研究领域:
药剂学
·
肿瘤学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
AAPS PHARMSCITECH
·
2022
·Vol. 23
·期 6
·1-13
·
IF 4.026
Ma Xiaojing,Wang Tong,Yu Zequan,Shao Junqian,Chu Jun,Zhu Huixia,Yao Risheng
Etoposide (ETO), a traditional anticancer chemotherapeutic agent, is commercialized in oral soft gelatin capsules and non-aqueous parenteral solutions form. Novel formulation application and new excipients exploration are needed to improve the water-solubility and comfort of the drug administration. In the present study, novel etoposide-loaded submicron emulsions (ESE) with the biosurfactants of acidic sophorolipid (ASL) and lactonic sophorolipid (LSL) instead of the chemical surfactant of Tween-80 were prepared and characterized. Firstly, parameters of medium-chain triglyceride: long-chain triglyceride (MCT:LCT), lecithin concentration, homogenization pressure and cycle, and type and concentration of surfactants were investigated to optimize the formation of ESEs. Then the physicochemical properties, antitumor activity, stability, and security of ESEs were compared. The results showed that ASL performed the best properties and activities than Tween-80 and LSL in ESE formation. ASL-ESE showed higher drug loading capacity, slower release rate, and significantly increased antitumor activity against ovarian cancer cell line A2780 via apoptosis than Tween-ESE and commercial ETO injection. Besides, both ASL-ESE and Tween-ESE caused no hemolysis, and the safe dose of ASL was 2.14-fold that of Tween-80 in the hemolysis test, making ASL more reliable for drug delivery applications. Furthermore, ASL-ESE exhibited equivalent long-term and autoclaving stability to Tween-ESE. These results thus suggested the excellent competences of ASL in ESE formation, efficacy enhancement, and safety improvement. Graphical abstract
研究领域:
药剂学
·
药物递送系统
·
癌症研究
·
生物技术
✓ 已验证
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
·
药学
·
纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2019
·
IF 8.355
Haixia Liu,Qingzhu Yang,Wei Guo,Huiming Lin,Feng Zhang,Jingxiang Zhao,Tianyue Ma,Le Zhao,Na Xu,Ruiwen Wang,Jingyao Yu,Fengyu Qu
Although phototherapy has received widespread attention in recent years due to its high efficiency, low invasiveness, and minor side effects, there are still few studies on the relationship between phototherapy and immunotherapy. Therefore, non-stoichiometric CoWO 4-x nanoparticles (NPs) were strategically designed and prepared, as these can simultaneously generate hyperthermia and reactive oxygen species (ROS) under near-infrared laser irradiation, illustrating that they can be used to realize photothermal therapy (PTT) and photodynamic therapy (PDT) on tumors. CoWO 4-x NPs not only have strong near-infrared absorption, outstanding biocompatibility, and excellent photothermal stability but they also can be used as photoacoustic (PA) and Computer Tomography (CT) contrast agents for working with tumors. In particular, the relationships between phototherapy, immunogenic cell death (ICD) and immunoresistance are here discussed in depth, and enhanced phototherapy was achieved for the first time by injecting etoposide and ML385, which are two typical inhibitors for HSP60 and NRF2, respectively. Furthermore, the biocompatibility of materials in vivo was demonstrated through a variety of cell experiments, changes in mouse body weight, and histological analyses. Our work highlights the great potentials of non-stoichiometric CoWO 4-x NPs as a kind of multifunctional therapeutic agent for implementing enhanced phototherapy in breast cancer by reducing the immunoresistance of HSP60 and NRF2 toward PTT and PDT.
研究领域:
纳米技术
·
癌症治疗
·
免疫学
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2022
·
IF 6.51
Lijing Sun,Liyuan Chen,Ke Yang,Wei Feng Dai,Ye Yang,Xiuming Cui,Bo Yang,Chengxiao Wang
In the current times, achieving specific targeted and controllable drug delivery remains one of the major challenges in the treatment of hepatocellular carcinoma (HCC). The present study reported the development of a multiple functional indocyanine green (ICG)‐cyclodextrin (CD) system, wherein loaded etoposide (EPS) was used as the model chemotherapeutic drug. In the developed system, ICG segment served as a photosensitizer for photothermal therapy (PTT) and the targeting moiety, which was primarily attributed to the specific retention properties in HCC tissues. The Ex vivo evaluation showed that ICG‐ [email protected] exhibited a laser‐triggered release profile with the photothermal efficiency and cytotoxicity towards HepG2 cells. In vivo evaluation suggested that ICG could navigate the systems to HCC tissues and retained at the site for 48 h, producing a drug accumulation in HCC. Further, laser irradiation boosted EPS release and local hyperthermia effects in HCC. Thus, the present study explored a novel and specific HCC targeting mechanism, and provided a feasible and controllable strategy for synergistic PTT and chemotherapy treatments for HCC.
研究领域:
癌症研究
·
药学
·
纳米技术
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMACROMOLECULES
·
2017
·
IF 5.246
Ding Qu,Lixiang Wang,Meng Liu,Shiyang Shen,Teng Li,Yuping Liu,Mengmeng Huang,Congyan Liu,Yan Chen,Ran Mo
The aim of this study is to demonstrate the enhanced therapeutic efficacy of anticancer drugs on drug-resistant breast cancer using multicomponent microemulsions (ECG-MEs) as an oral delivery system. The etoposide-loaded ECG-MEs were composed of coix seed oil and ginsenoside Rh2 (G-Rh2), both of which possess not only the synergistic antitumor effect with etoposide, but also have excipient-like properties. Orally administrated ECG-MEs were demonstrated to be able to accumulate at the tumor site following crossing the intestines as intact vehicles into the blood circulation. The spatiotemporal controlled release characteristics of ECG-MEs brought about the efficient P-gp inhibition by the initially released G-Rh2 and the increased intracellular accumulation of the sequentially released etoposide. The combination antitumor activity of etoposide, G-Rh2 and coix seed oil using ECG-MEs was verified on the xenograft drug-resistant breast tumor mouse models. In addition, the safety evaluation studies indicated that treatment with ECG-MEs did not cause any significant toxicity in vivo. These findings suggest that ECG-MEs as an oral formulation may offer a promising strategy to treat the drug-resistant breast cancer.
研究领域:
药学
·
肿瘤学
·
纳米技术
·
药物递送系统
✓ 已验证
DOI
PubMed
高影响因子
Applied Materials Today
·
2022
·
IF 8.663
Xiyou Du,Yu Zhang,Yanan Zhang,Shan Gao,Xiaoye Yang,Lei Ye,Guangxi Zhai
Tumor microenvironment (TME) featured by dense extracellular matrix (ECM), high interstitial pressure, hypoxia, and immunosuppression hinders the infiltration of nanoparticles (NPs) into tumors, impairing the efficacy of chemotherapy or phototherapy. To overcome these obstacles, we propose a novel biomimetic nano-carrier, B16F10 cell membrane camouflaged heparin-3-bromopyruvate conjugate modified graphene oxide (GO [email protected] , GBM), for the targeted delivery of etoposide (EPT). EPT/GBM accumulates in tumor tissue and is internalized into B16F10 cells relying on homologous targeting ability. GO-mediated hyperthermia could accelerate the release of EPT, destruct ECM, dilate blood vessels, increase oxygen supply, and induce immunogenic cell death (ICD). The acylhydrazone bond-conjugated 3BP is released in acidic environment, suppressing glycolysis for starvation therapy, and reducing lactate efflux to alleviate immunosuppression. The released EPT entered the cell nuclei to exert a chemotherapeutic effect and downregulated the expression of programmed death ligand 1 (PD-L1) by inhibiting epithelial-mesenchymal transition (EMT)/β-catenin/STT3/PD-L1 signaling. EPT/GBM plus near infrared (NIR) laser treatment activated T lymphocytes and downregulated M2 tumor-associated macrophage (TAM), showing significant efficacy against primary tumors, abscopal tumors and lung metastases. In summary, this study presented a novel combinational strategy that integrated PTT, chemotherapy, starvation therapy and immunotherapy in one system, providing a new perspective for targeted-therapy of melanoma.
研究领域:
纳米技术
·
肿瘤学
·
生物医学工程
·
药学
·
材料科学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）