INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2021
·
IF 5.875
Siyu Sun,Xiyou Du,Manfei Fu,Abdur Rauf Khan,Jianbo Ji,Weidong Liu,Guangxi Zhai
In this study, galactosamine-modified poly(ethylene glycol)-poly(lactide) (Gal-PEG-PLA) polymers were synthesized and Gal-PEG-PLA/D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) micelles named as GPP micelles were designed to promote the oral absorption of a hydrophobic drug, curcumin (CUR). CUR-loaded Gal-PEG-PLA/TPGS micelles (CUR@GPP micelles) were fabricated using the thin-film dispersion method. CUR@GPP micelles had a size of about 100 nm, a near-neutral zeta potential , drug loading (DL) of 14.6%, and sustained release properties. GPP micelles with high Gal density (GPP3 micelles) were superior in facilitating uptake in epithelial cells and improving intestinal permeation. In situ intestinal absorption studies suggested that the jejunum and ileum were the best absorption segments in the intestinal tract. Additionally, biodistribution results revealed that GPP3 micelles could be remarkably taken up by the jejunum and ileum. Pharmacokinetics revealed that the maximum plasma concentration (C max ) and the area under the plasma concentration-time curve from 0 to 24 h (AUC 0–24 ) for CUR@GPP3 micelles were both significantly increased, and that the relative bioavailability of CUR@GPP3 micelles to CUR-loaded mPEG-PLA/TPGS micelles (CUR@PP micelles) was 258.8%. Furthermore, CUR-loaded micelles could reduce damage to the liver and intestinal tissues. This study highlights the importance of Gal content in the design of targeting nanocarrier Gal-modified micelles, which have broad prospects for oral delivery of hydrophobic drugs. Therefore, they could serve as a promising candidate for targeted delivery to the liver.
研究领域:
药剂学
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生物医学工程
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DOI
高影响因子
JOURNAL OF DRUG TARGETING
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2025
·
IF 3.9
Hong Chen,Michael Adu-Frimpong,Lili Yuan,Yaping Yang,Jollibekov Berdiyar,Jiangnan Yu,Xia Cao,Qilong Wang,Ximing Xu
Astragaloside, a natural flavonol glycoside isolated from plants, exhibits significant tumour-suppressive activity. However, its low solubility and poor bioavailability have hindered its practical application. To improve its bioavailability and therapeutic efficacy, this study prepared Ast-loaded Soluplus/TPGS/Gas hybrid polymer micelles (Ast-STG-M) via the thin-film hydration method. The resulting Ast-STG-M nanoparticles were spherical and uniformly dispersed, characterised by a small particle size (50.92 ± 0.13 nm) and a high encapsulation efficiency (95.24 ± 0.53%). In vitro release profiles demonstrated that the cumulative release rate of Ast from Ast-STG-M was higher than that of free Ast under various pH conditions. After oral administration, compared with free Ast, Ast-STG-M exhibited delayed in vivo elimination and significantly increased bioavailability. Furthermore, results from in vitro and in vivo anti-tumour studies indicated that Ast-STG-M could significantly inhibit the viability of TPC-1 cells, thereby effectively suppressing the growth of solid tumours. In conclusion, Ast-STG-M holds substantial potential as a delivery system for Ast to tumour sites, which not only enhances the oral bioavailability of Ast but also strengthens its anti-cancer activity.
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PubMed
高影响因子
ACS Omega
·
2024
·
IF 3.7
Hui-Qin Liu,Xi-Dong Wu,Xue-Wen Fang,Yun-Song An,Meng Xia,Xiao-Hua Luo,Jun-Zheng Li,Guan-Hai Wang,Tao Liu
Nasopharyngeal carcinoma (NPC) is prevalent in Southern China. Unfortunately, current treatments encounter multidrug resistance (MDR). Overexpression of P-glycoprotein (P-gp), resulting in the efflux of chemotherapy drugs, is one of the significant mechanisms causing MDR. d-α-Tocopheryl poly(ethylene glycol) 1000 succinate (TPGS) has been demonstrated to effectively inhibit P-gp expression. The objectives of this study are to improve tumor MRI imaging, optimize docetaxel (DOC) administration, and target P-gp to overcome NPC resistance. Multifunctional micelles of TPGS (MM@DOC), loaded with magnetic nanoparticles, were synthesized for the targeted delivery of the first-line anticancer drug. MM@DOC exhibited greater toxicity and induced higher levels of apoptosis in DOC-resistant NPC cells (C666–1/DOC) compared to DOC. MM@DOC loaded with magnetic nanoparticles improved the quality of tumor MRI imaging. MM@DOC also demonstrated significant antitumor effects in nude mice with C666–1/DOC NPC. In conclusion, MM@DOC exhibited promising inhibitory effects on resistant tumors both in vitro and in vivo, optimized tumor MRI imaging, and showed great potential in drug delivery and overcoming resistance.
研究领域:
肿瘤学
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医学影像学
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药物递送系统
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DOI
PubMed
高影响因子
NANOTECHNOLOGY
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2017
·Vol. 28
·期 19
·195602
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IF 3.44
Altansukh Tsend-Ayush,Xiumei Zhu,Yu Ding,Jianxu Yao,Lifang Yin,Jianping Zhou,Jing Yao
Many effective anti-cancer drugs have limited use in hepatocellular carcinoma (HCC) therapy due to the drug resistance mechanisms in liver cells. In recent years, tumor-targeted drug delivery and the inhibition of drug-resistance-related mechanisms has become an integrated strategy for effectively combating chemo-resistant cancer. Herein, lactobionic acid-conjugated d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS-LA conjugate) has been developed as a potential asialoglycoprotein receptor (ASGPR)-targeted nanocarrier and an efficient inhibitor of P-glycoprotein (P-gp) to enhance etoposide (ETO) efficacy against HCC. The main properties of ETO-loaded TPGS-LA nanoparticles (NPs) were tested through in vitro and in vivo studies after being prepared using the nanoprecipitation method and characterized by dynamic light scattering (DLS). According to the results, smaller (∼141.43 nm), positively charged ETO-loaded TPGS-LA NPs were more suitable for providing efficient delivery to hepatoma cells by avoiding the clearance mechanisms. It was found that ETO-loaded TPGS-LA NPs were noticeably able to enhance the cytotoxicity of ETO in HepG2 cells. Besides this, markedly higher internalization by the ASGPR-overexpressed HepG2 cells and efficient accumulation at the tumor site in vivo were revealed in the TPGS-LA NP group. More importantly, animal studies confirmed that ETO-loaded TPGS-LA NPs achieved the highest therapeutic efficacy against HCC. Interestingly, ETO-loaded TPGS-LA NPs also exhibited a great inhibitory effect on P-gp compared to the ETO-loaded TPGS NPs. These results suggest that TPGS-LA NPs could be used as a potential ETO delivery system against HCC.
研究领域:
药学
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纳米技术
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肿瘤学
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药物递送系统
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DOI
PubMed
高影响因子
Nanomedicine-Nanotechnology Biology and Medicine
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2016
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IF 5.671
Xin Jin,Mengying Li,Lifang Yin,Jianping Zhou,Zhenhai Zhang,Huixia Lv
Tyroservatide (YSV) is a tripeptide that has been approved for clinical testing, as a new anticancer drug . In the current study, YSV-stearic acid (YSV-SA) was inserted into the surface of d -alpha-tocopheryl polyethylene glycol 1000 succinate monoester (TPGS)-modified paclitaxel (PTX) liposomes (TP-Lip) to form YSV-conjugated TP-Lip (TYP-Lip). Both in vivo imaging and in vitro cell uptake analysis indicated that these modifications could increase tumor-targeting and cell uptake of the liposomes. Optimal antitumor effects were achieved via tail vein injections of TYP-Lip in MB-231 tumor-bearing nude mice . Overall, the formed TYP-Lip not only achieved a synergistic anticancer effect through YSV and PTX, but also improved tumor-targeting and exhibited further antitumor capabilities. These results indicated that combining biological (YSV) and chemotherapeutic (PTX) agents is an efficient combinatorial delivery strategy for enhanced tumor targeting and synergistic antitumor effects.
研究领域:
药学
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肿瘤学
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药物递送系统
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DOI
PubMed
高影响因子
Nature Communications
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2022
·Vol. 13
·期 1
·1-17
·
IF 17.694
Wang Xiaojuan,Xu Xiaoling,Zhang Shaojun,Chen Na,Sun Yunfeng,Ma Kuifen,Hong Dongsheng,Li Lu,Du Yongzhong,Lu Xiaoyang,Jiang Saiping
Tigecycline is regarded as the last line of defense to combat multidrug-resistant Klebsiella pneumoniae . However, increasing utilization has led to rising drug resistance and treatment failure. Here, we design a D-alpha tocopheryl polyethylene glycol succinate-modified and S-thanatin peptide-functionalized nanorods based on calcium phosphate nanoparticles for tigecycline delivery and pneumonia therapy caused by tigecycline-resistant Klebsiella pneumoniae . After incubation with bacteria, the fabricated nanorods can enhance tigecycline accumulation in bacteria via the inhibitory effect on efflux pumps exerted by D-alpha tocopheryl polyethylene glycol succinate and the targeting capacity of S-thanatin to bacteria. The synergistic antibacterial capacity between S-thanatin and tigecycline further enhances the antibacterial activity of nanorods, thus overcoming the tigecycline resistance of Klebsiella pneumoniae . After intravenous injection, nanorods significantly reduces the counts of white blood cells and neutrophils, decreases bacterial colonies, and ameliorates neutrophil infiltration events, thereby largely increasing the survival rate of mice with pneumonia. These findings may provide a therapeutic strategy for infections caused by drug-resistant bacteria.
研究领域:
药学
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纳米技术
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传染病学
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生物医学工程
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PubMed
高影响因子
Frontiers in Pharmacology
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2018
·
IF 3.831
Tsai Hsiang-I,Jiang Lijuan,Zeng Xiaowei,Chen Hongbo,Li Zihuang,Cheng Wei,Zhang Jinxie,Pan Jie,Wan Dong,Gao Li,Xie Zhenhua,Huang Laiqiang,Mei Lin,Liu Gan
The clinical applications of platinum-based antitumor agents are still largely limited by severe side effects as well as multidrug resistance (MDR). To solve these problems, we developed an 1,2-diaminocyclohexane-platinum(II) (DACHPt)-loaded nanoparticle (NP-TPGS-Pt) by self-assembly of poly(amidoamine)-polyglutamic acid-b-D-α-tocopheryl polyethylene glycol 1000 succinate (PAM-PGlu-b-TPGS) and DACHPt. NP-TPGS-Pt showed robust stability and pH-responsive DACHPt release profile in vitro similar to the PEG-containing nanoparticle (NP-PEG-Pt). Meanwhile, in contrast with NP-PEG-Pt, NP-TPGS-Pt exhibited efficient nanoparticle-based cellular uptake by the Pt-resistant A549/DDP human lung cancer cells and caused much more cytotoxicity than free Oxaliplatin and NP-PEG-Pt. Finally, this NP-TPGS-Pt was proved to perform outstanding inhibition of Pt-resistant tumor growth, much superior than free Oxaliplatin and NP-PEG-Pt. Thus, this NP-TPGS-Pt provides a novel powerful nanomedicine platform for combatting multidrug resistant cancer.
研究领域:
药学
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肿瘤学
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纳米医学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2019
·
IF 4.213
Zhonghui Xie,Zhenhai Zhang,Huixia Lv
Rapamycin as a novel macrolide immunosuppressive agent has been commonly used in organ transplantation owing to its stronger immunosuppressive effect, non-nephrotoxicity and lower side effect. However its drawbacks of low bioavailability and big individual difference remain to be improved in clinical application. Here rapamycin loaded TPGS-Lecithins-Zein nanoparticles (RTLZ-NPs) with core-shell structure were prepared by the phase separation method. The RTLZ-NPs were approximately 190.3 nm in size, with PDI and zeta potential about 0.256 and −19.71 mV respectively. Drug entrapment and loading achieved were about 86.64 and 25.73% respectively. Meanwhile RTLZ-NPs exhibited favorable enzymolysis resistance abilities in gastrointestinal environments and enhanced uptake in Caco-2 cells. The optimum absorption sites of rapamycin in the intestine were duodenum and jejunum as single-pass intestinal perfusion assay. Upon also considering the results of Caco-2 cell assay, it could be speculated that the transport of rapamycin in vivo involved active transport as well as P-glycoprotein (P-gp) based efflux. Finally, the relative oral bioavailability of RTLZ-NPS was 4.33 fold higher than free rapamycin in SD rat . Altogether the designed nanoparticles can be an efficient oral delivery strategy for rapamycin analogues to prevent the attacks from destructive enzymes, reduce cell efflux, increase cell uptake, and then enhance the oral bioavailability.
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PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2016
·
IF 7.441
Yuling Bao,Mingxing Yin,Xiaomeng Hu,Xiangting Zhuang,Yu Sun,Yuanyuan Guo,Songwei Tan,Zhiping Zhang
A pH-sensitive prodrug , TPGS-CH N -DOX, was introduced by conjugating anticancer drug , doxorubicin (DOX), onto d -α-tocopherol polyethylene glycol 1000 succinate (TPGS) via a cleavable Schiff base linkage. The prodrug was mixed with a PEGylated lipid to form a simple but multifunctional hybrid micelle system, which can realize high drug loading capability and biocompatibility , extended blood circulation time, inhibited drug resistance in cancer cells, improved therapeutic response, reduced side effects, and easy functionalities for targeting delivery. The hybrid micelles exhibited in vitro pH-sensitive drug release, enhanced cellular uptake and strengthened cytotoxicity on both drug-sensitive human breast cancer MCF-7 and resistant MCF-7/ADR cells. P-glycoprotein functional inhibition and mitochondria-associated cell apoptosis induced by TPGS were thought to play an important role in overcoming the multidrug resistance . As a result, the hybrid micelles demonstrated good anticancer efficacy in MCF-7/ADR xenograft model. Additionally, after modifying with a tumor-specific targeting peptic ligand, cRGD, the tumor growth/metastasis inhibition was further evidenced in integrin receptor overexpressed melanoma cancer B16F10 and even murine hepatocarcinoma H22 models. This TPGS-based pH-sensitive prodrug provides a safe and “Molecular economical” way in the rational design of prodrugs for overcoming multidrug resistance and targeting delivery, which can improve the potency for clinical use.
研究领域:
药学
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肿瘤学
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生物医学工程
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DOI
PubMed
高影响因子
Asian Journal of Pharmaceutical Sciences
·
2021
·
IF 6.598
Haoshi Gao,Yan Su,Wei Wang,Wei Xiong,Xiyang Sun,Yuanhui Ji,Hua Yu,Haifeng Li,Defang Ouyang
Current formulation development strongly relies on trial-and-error experiments in the laboratory by pharmaceutical scientists, which is time-consuming, high cost and waste materials. This research aims to integrate various computational tools, including machine learning, molecular dynamic simulation and physiologically based absorption modeling (PBAM), to enhance andrographolide (AG) /cyclodextrins (CDs) formulation design. The lightGBM prediction model we built before was utilized to predict AG/CDs inclusion's binding free energy. AG/γ-CD inclusion complexes showed the strongest binding affinity, which was experimentally validated by the phase solubility study. The molecular dynamic simulation was used to investigate the inclusion mechanism between AG and γ-CD, which was experimentally characterized by DSC, FTIR and NMR techniques. PBAM was applied to simulate the in vivo behavior of the formulations, which were validated by cell and animal experiments. Cell experiments revealed that the presence of D-α-Tocopherol polyethylene glycol succinate (TPGS) significantly increased the intracellular uptake of AG in MDCK-MDR1 cells and the absorptive transport of AG in MDCK-MDR1 monolayers. The relative bioavailability of the AG-CD-TPGS ternary system in rats was increased to 2.6-fold and 1.59-fold compared with crude AG and commercial dropping pills, respectively. In conclusion, this is the first time to integrate various computational tools to develop a new AG-CD-TPGS ternary formulation with significant improvement of aqueous solubility, dissolution rate and bioavailability. The integrated computational tool is a novel and robust methodology to facilitate pharmaceutical formulation design.
研究领域:
药剂学
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计算生物学
·
药物化学
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产品关联
DOI
PubMed
高影响因子
REACTIVE & FUNCTIONAL POLYMERS
·
2022
·
IF 4.966
Guoguang Chen,Qiqi Zheng,Jie Dai,Jia Liu,Jun Yin,Xiaoqing Xu,Aiping Chen,Lili Ren
Currently, the drawbacks of the chemotherapy drugs are still demonstrated poor water solubility, systemic toxicity and even multidrug resistance (MDR) in clinical applications. To address these problems, an amphiphilic block polymer self-assembled reduction sensitive micelle , mPEG-SS-PzLL/TPGS/DOX, was synthesized for efficient anticancer therapy. The polymer had a biodegradable backbone and disulfide bond can be cleaved by reduced glutathione (GHS) in tumor cells, which led to fast release of the DOX . TPGS was designed for an increaseing drug accumulation and a reduction in drug efflux. In follow-up research, we found that mPEG-SS-PzLL/TPGS/DOX micelles achieved a high encapsulation efficiency of 96.1%. Photomicrographs gotten by TEM showed homogeneous and spherical-shaped particles with the particl size of 83.7 ± 3.2 nm. The in vitro release in high reducing conditions reached 96% within 48 h. Furthermore, the mPEG-SS-PzLL/TPGS/DOX micelles caused stronger cytotoxicity to 4 T1 cells and promising therapeutic efficacy for BALB/c mice bearing 4 T1 tumors. Therefore, an excellent drug delivery system was created by combing restore sensitivity with multidrug resistance strategy while maximize drug accumulation in tumor cells. Alternatively, this study offers a bright perspective for cancer therapy with chemotherapeutics.
研究领域:
药学
·
肿瘤学
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DOI
高影响因子
International Journal of Nanomedicine
·
2023
·
IF 8
Xin Jin,Qing Yang,Youwen Zhang
To develop an alternative treatment for lung cancer, a combination of two potent chemotherapeutic agents – liposomal apigenin and tyroservatide – was developed. The therapeutic potential of this combination was investigated using A549 cells. Apigenin and tocopherol derivative-containing D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) liposomes might improve the delivery of apigenin to tumor cells, both in vitro and in vivo. Importantly, compared to either agent alone, the combination of apigenin TPGS liposomes and tyroservatide exhibited superior cytotoxicity, induced stronger G2 arrest, and suppressed A549 cancer cell invasion at a lower dose. The proapoptotic synergistic effects were also observed in A549 cells using terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling, flow cytometry, and Western blot analysis. More importantly, in vivo results showed that the combination of apigenin TPGS liposomes and tyroservatide exhibited tumor-growth inhibitory effects in A549 cell-bearing mice. In conclusion, our study showed that this combination therapy could serve as a promising synergistic therapeutic approach to improve outcomes in patients with lung cancer.
研究领域:
肿瘤学
·
药学
·
分子生物学
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DOI
PubMed
高影响因子
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