BIOMEDICINE & PHARMACOTHERAPY
·
2023
·
IF 7.5
Xinhao Song,Mengjuan Lin,Tian Fang,Jiahao Gong,Junqi Wang,Shasha Gao,Xiaolin Xu,Xin Lv,Xiuge Gao,Junren Zhang,Shanxiang Jiang,Dawei Guo
Canine mammary tumors (CMT) can severely compromise the life quality of the affected dogs through local recurrence, distant metastases and ultimately succumb to death. Recently, more attention has been given to the potential antimetastatic effect of maduramicin (MAD) on breast cancer. However, its poor aqueous solubility and toxicity to normal tissues limit its clinical application. Therefore, to address the drawbacks of MAD and enhance its anticancer and antimetastatic effects, MAD-loaded TPGS polymeric micelles (MAD-TPGS) were prepared by a thin-film hydration technique. The optimized MAD-TPGS exhibited excellent size distribution, stability and improved water solubility. Cellular uptake assays showed that TPGS polymer micelles could enhance drug internalization. Moreover, TPGS synergistically improved the cytotoxicity of MAD by targeting mitochondrial organelles, improving reactive oxygen species levels and reducing the mitochondrial transmembrane potential. More importantly, MAD-TPGS significantly impeded the metastasis of tumor cells. In vivo results further confirmed that, in addition to exhibiting excellent biocompatibility, MAD-TPGS exhibited greater antitumor efficacy than free MAD. Interestingly, MAD-TPGS displayed superior suppression of CMT metastasis via tail vein injection compared to oral administration, indicating its suitability for intravenous delivery. Overall, MAD-TPGS could be applied as a potential antimetastatic cancer agent for CMT.
研究领域:
药学
·
癌症研究
·
纳米技术
·
兽医学
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产品关联
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2025
·
IF 4.5
Shuang Yang,Beibei He,Cuiping He,Fengye Zhao,Ran Li,Minfei Shi,Bin Zheng
As a potential drug, antisense oligonucleotides (AO) have considerable application prospects in the field of tumor treatment. However, the main problem to be solved is the lack of an efficient and safe carrier that contributes to reaching the target cancer cells and utilizing the antitumor effect of AO. Here, we designed and developed a novel AO delivery system, which was based on a modified polyethylenimine (PEI) named TPGS-SS-PEI by connecting tocopherol polyethylene glycol succinate (TPGS) to PEI through the disulfide bond (SS) and the biomimetic red blood cell membrane vesicles (RVs). R-TSP/AO was composed of an AO-loaded micelle (TSP/AO) as the “core” prepared by TPGS-SS-PEI, and RVs as the “shell”. The formulations and properties of R-TSP/AO were optimized and characterized. The mean particle size and zeta potential of R-TSP/AO were 109.7 nm and −24.10 mV, respectively. In vitro studies indicated that R-TSP/AO was sensitive to highly reducing conditions and exhibited excellent stability and high security. In addition, R-TSP showed higher AO transfection efficiency and excellent gene silencing efficiency compared with unmodified PEI (P < 0.001). R-TSP/AO exhibited potent tumor inhibition (55.65%) in 4T1 tumor-bearing mice without inducing systemic toxicity. These findings suggested that R-TSP/AO was safe and efficient in enhancing the antitumor efficacy and R-TSP had the potential to be further researched as a carrier for nucleic acid drugs delivery.
研究领域:
药剂学
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纳米技术
·
分子治疗学
·
生物医学工程
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2022
·
IF 5.062
Wan Liu,Meng Cheng,Fangying Yuan,Jiaying He,Yulin Feng,Yi Jin,Jianfang Feng,Shilin Yang,Liangxing Tu
Nanocrystal technology is a common strategy to enhance the oral bioavailability of poorly-soluble drugs, and how to enlarge the enhancing ability on oral absorption via nanocrystals has become a pharmaceutical research field. In this study, we selected andrographolide (ADR), a typical poorly-soluble drug, as the model drug, and employed sodium dodecyl sulfate and D-ɑ-Tocopherol polyethylene glycol 1000 succinate copolymer (SDS-TPGS) to construct novel SDS-TPGS modified andrographolide nanocrystals (S-TANs). We found that the particle sizes of SDS/TPGS physical mixture modified nanocrystals (STANs) were about 553.4 ± 4.1 nm , while that of SDS-TPGS modified nanocrystals (S-TANs) were 604.6 ± 5.7 nm. During the production process of nanocrystals, the crystallinity of ADR was slightly decreased. Nanocrystals enhanced the saturation solubility of ADR, and improved oral absorption, C max and AUC 0-∞ of S-TANs was about 2.10 and 1.24 fold increased, STAN about 2.63, 2.97 fold. In a Real-time distribution study, we found the distribution time of andrographolide, SDS and TPGS in SDS/TPGS physical mixture modified nanocrystals system varies widely, while the distribution times of these materials were similar in SDS-TPGS copolymer modified nanocrystals system. These results indicated that modified with functional stabilizer was an efficient strategy to enlarge the enhancing ability on oral absorption of nanocrystals, and synthesized copolymer containing different functional stabilizers showed higher ability on enhancing oral bioavailability than physical mixtures.
研究领域:
药学
·
纳米技术
·
药物递送系统
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2014
·
IF 3.785
Xin-Jiang Tang,Min Han,Bo Yang,You-Qing Shen,Zhong-Gui He,Dong-Hang Xu,Jian-Qing Gao
Camptothecin (CPT) nanosuspension was prepared by anti-solvent precipitation with TPGS as stabilizer to improve the solubility, stability and antitumor activity of CPT. And an increased solubility, stability and dissolution rate was achieved after nanosuspension being prepared. While, enhanced intracellular accumulation and cellular cytotoxicity was also observed for CPT nanosuspension than that of CPT solution.In addition, nanosuspension could increase bioavailability and intratumor accumulation of CPT in vivo after intravenous administration, and then produced a much higher antitumor effect and biocompatibility than that of CPT solution. Meanwhile, an enhanced cellular CPT uptake in hypoxic or acid conditions could also be observed for nanosuspension. As a result, nanosuspension represents a potentially feasible formation for insoluble drug in antitumor research.
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
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2020
·
IF 4.845
Tian'e Chen,Liangxing Tu,Ge Wang,Na Qi,Wei Wu,Wei Zhang,Jianfang Feng
Chitosan is widely used as a permeation enhancer for oral drug delivery, although its drawbacks include a limited enhancement of drug bioavailability and an inability to form micelles. In this study, we designed a novel chitosan derivative (GA-CS-TPGS copolymer) and constructed paclitaxel micelles (PTX-Micelles) designed to have multiple functions associated with the GA-CS-TPGS copolymer (enhanced bioadhesion, inhibited P-gp efflux and drug metabolism in liver) and the micelles (enhanced solubility and permeability) to enhance the bioavailability and anti-tumor efficacy of PTX. The results showed that the PTX-Micelles system could alter the in vivo pharmacokinetic performance and therapeutic effect of PTX via its predesigned functions. The bioavailability of PTX was enhanced approximately 3.80-fold by the PTX-Micelles, and an enhanced anti-lung tumor efficacy of PTX-Micelles was observed when compared to Taxol®. The results of this study indicate that constructing micelles with a multifunctional chitosan derivative may be a promising approach to enhance the oral bioavailability and anti-tumor efficacy of poorly soluble drugs.
研究领域:
药剂学
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药物递送系统
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药理学
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2023
·
IF 9.5
Ping Shen,Xinyi Zhang,Ni Ding,Yinhua Zhou,Changquan Wu,Chengyuan Xing,Ling Zeng,Lixin Du,Jianpeng Yuan,Yang Kang
Conventional chemotherapy usually fails to achieve its intended effect because of the poor water solubility, poor tumor selectivity, and low tumor accumulation of chemotherapy drugs. The systemic toxicity of chemotherapy agents is also a problem that cannot be ignored. It is expected that smart nano-drug delivery systems that are able to respond to tumor microenvironments will provide better therapeutic outcomes with decreased side effects of chemotherapeutics. Nano-drug delivery systems capable of breaking the redox balance can also increase the sensitivity of tumor cells to chemotherapeutics. In this study, using polymer-containing disulfide bonds, ester bonds, and d-α-tocopherol polyethylene glycol succinate (TPGS), which can amplify reactive oxygen species (ROS) in tumor cells, we have successfully prepared a smart glutathione (GSH) and esterase dual-responsive nano-drug delivery system (DTX@PAMBE-SS-TPGS NPs) with the ability to deplete GSH as well as amplify ROS and effectively release an encapsulated chemotherapy drug (DTX) in tumor cells. The potential of DTX@PAMBE-SS-TPGS NPs for enhanced antitumor effects was thoroughly evaluated using in vitro as well as in vivo experiments. Our research offers a promising strategy for maximizing the efficacy of tumor therapy.
研究领域:
药理学
·
纳米技术
·
肿瘤学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2018
·Vol. 6
·期 21
·3586-3599
·
IF 4.776
Xiaoqin Chen,Jing Sun,Huan Zhao,Ke Yang,Yuda Zhu,Hongrong Luo,Kui Yu,Hongsong Fan,Xingdong Zhang
For synchronous theranostic systems, there are two areas of focus. These are: excellent in vivo imaging and a multi-drug resistance (MDR) reversing ability for chemotherapy. Upconversion nanoparticles (UCNPs) exhibiting bright red emission in the “optical window in biological tissue (600–1100 nm)” could be a very useful candidate, although there have only been a few reports on UCNP-based conjugates with a MDR reversal ability explored for chemotherapy. Herein, we report an innovative theranostic system (D-UNT) via binding of an antitumor drug (DOX) and a MDR reversal agent (TPGS) to NaY(Mn)F4:Yb/Er UCNPs (UN) with synthetic optimized red emission and properties. The in vitro study demonstrated that the D-UNT was uptaken into drug-resistant MCF-7/ADR cells via caveolin dependent endocytosis and overcame P-gp mediated efflux. The cytotoxicity was significantly promoted to be much higher than that of free DOX. Accordingly, our D-UNT illustrates an enhanced reversal ability for chemotherapy. Our in vivo study further indicated that the D-UNT had excellent therapeutic efficacy against MDR tumors with minimal organ toxicity detected. In vivo deep-tissue imaging showed that the D-UNT accurately diagnosed MDR tumors at a 1.5 cm depth with high-contrast luminescent signals. Thus, the D-UNT is an effective theranostic system for the diagnosis and therapeutic treatment of MDR tumors. The present work opens new pathways to engineering powerful theranostic agents to simultaneously target, image and kill deep-tissue MDR tumor cells.
研究领域:
纳米技术
·
癌症研究
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药学科学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Bio Materials
·
2020
·
IF 0
Zhicheng Le,Zhijia Liu,Lilong Sun,Lixin Liu,Yongming Chen
Dysregulated inflammation is considered as an essential pathological process in inflammation-associated diseases, which would be aggravated by high levels of reactive oxygen species (ROS) generation inducing oxidative stress. Currently, extensive attention has been paid to polyphenolic compounds owing to their broad spectrum biological activities, such as antioxidant and anti-inflammatory effects, while their therapeutic potential has been compromised by the poor stability, short plasma half-life, and low bioavailability. Given that polyphenols have a wide range of structural characteristics and various physicochemical properties, there remains a real challenge toward green, mass production of universal nanocarriers for effective entrapment of these active pharmaceutical ingredients. In this study, we adopted a flash nanocomplexation (FNC) platform to prepare nanocomplexes comprising polyphenols and d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) enabled by hydrogen bonding. We confirmed that the molecular structure of polyphenols has a great influence on their complexation with TPGS, and stable nanocomplexes were formed when the number of phenolic hydroxyl groups of polyphenols was above the value of 8. These hydrogen-bonded nanocomplexes produced by an FNC apparatus exhibited well-controlled quality with uniform size, good colloidal stability, and high batch-to-batch repeatability, thus improving the druggability as potent nanotherapeutics for antioxidant and anti-inflammatory applications. In vivo experiments indicated that the optimal nanocomplex (EGCG-NC) can be applied to ameliorate acute lung injury in a mice model after nasal administration. These results proved that polyphenols formulated with TPGS for nanocomplex formation through hydrogen-bonding complexation could augment their therapeutic potential for modulating hyperactive inflammation in the treatment of acute lung inflammation.
研究领域:
药理学
·
纳米技术
·
炎症
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
Biomaterials Advances
·
2024
·
IF 5.5
Rongli Chen,Ergang Liu,Yuefei Fang,Nan Gao,Meng Zhang,Xiaoru Zhang,Wanying Chen,Chuxin Liang,Yu Zhang,Yongzhuo Huang
The marketed paclitaxel (PTX) formulation Taxol relies on the application of Cremophor EL as a solubilizer. The major drawback of Taxol is its hypersensitivity reactions and a pretreatment of anti-allergic drugs is a necessity. Therefore, developing an efficient and safe delivery vehicle is a solution to increase PTX treatment outcomes with minimal adverse effects. In this work, we prepared the amphiphilic peptides (termed AmP) from soybean proteins using a facile two-step method. AmP could efficiently solubilize PTX by self-assembling into mixed micelles with D-α-tocopherol polyethylene glycol succinate (TPGS), a common pharmaceutical expedient (PTX@TPGS-AmP). The intravenously administrated PTX@TPGS-AmP exhibited a slow clearance (0.24 mL·(min·kg) −1 ) and an enhanced AUC (41.4 μg.h/mL), manifesting a 3.6-fold increase compared to Taxol. In a murine 4T1 tumor model, PTX@TPGS-AmP displayed a superior antitumor effect o v er Taxol. Importantly, safety assessment showed a high biocompatibility of AmP and an i.v. dose up to 2500 mg/kg led to no observable abnormalities in the mice. In summary, the AmP presents a new green and easily-prepared amphiphilic biomaterial, with promising potential as a pharmaceutical excipient for drug delivery.
研究领域:
药学
·
肿瘤学
·
药物递送系统
·
生物技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MATERIALS & DESIGN
·
2024
·
IF 7.6
Biao Li,Weicheng Zhou,Xinmin Wang,Wanyi Zhong,Qin Zheng,Yingchong Chen,Pengfei Yue
Mucus clearance, epithelium mucosal barrier and P-glycoprotein (P-gp) efflux are the main gastrointestinal barriers that limit the oral delivery of nanoparticles. Inspired by tunable particles surface properties-dependent trans -mucus and trans -mucosal abilities, novel bilayer-functionalized mesoporous silica nanoparticles (MSN) containing D- α -tocopheryl polyethylene glycol succinate (TPGS) and sulfobetaine 12 (SB12) were designed by layer-to-layer assembly. The amino-grafted MSN (MSN-NH 2 ) was firstly functionalized with TPGS as hydrophobic layer (MSN-TPGS), and then SB12 was self-assembled on the hydrophobic surface of MSN-TPGS to generate a neutral and hydrophilic MSN (MSN-TPGS@SB12). Compared with MSN-NH 2 , MSN-TPGS, and MSN-TPGS@P123, the MSN-TPGS@SB12 possessed “one stone three birds” functions that enhanced mucus penetration, increased trans -mucosal absorption, as well as suppressed P-gp efflux. The pharmacokinetics study demonstrated that the MSN-TPGS@SB12 loading puerarin (MSN-TPGS@SB12-PUE) exhibited much higher bioavailability compared to other PUE-loaded formulations. Furthermore, the MSN-TPGS@SB12-PUE could significantly enhance the anti-inflammatory efficacy of PUE in vitro and in vivo . In summary, bilayer-functionalized MSN-TPGS@SB12 is a promising vehicle for overcoming the multiple gastrointestinal barriers (mucus clearance, intestinal epithelium barrier and P-gp efflux). Meanwhile, this study also provides a better understanding of the importance of tunable surface property of MSN on oral delivery of drugs.
研究领域:
纳米技术
·
药学
·
生物医学工程
✓ 已验证
DOI
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2022
·
IF 5.062
Dickson Pius Wande,Yue Qiu,Shijie Chen,Lan Yao,Yanghui Xu,Jing Yao,Hui Xiong
Oxaliplatin (OXA) and rapamycin (RAPA) combination therapy have shown the advantages of synergistically inhibiting the growth of cancer cells by enhancing apoptosis in cancerous cell lines. However, drug resistance and the lack of an orally administered formulation which exhibited the best clinical dosing compliance limited the clinical application of this regimen. Here, we report a nanogel-polymersomes drug delivery system (i.e.TMOR-CDAN) based on modified chitosan, chitosan diacetate (CDA), methoxy-poly-(ethylene glycol)-b-poly (lactide) (MPP), and D-alpha-tocopheryl polyethylene glycol succinate (TPGS) with permeation-glycoprotein (P-gp) inhibition capability for enhancing the oral chemotherapy efficacy of erroneously soluble RAPA and its synergistic chemotherapy with OXA. Hydrophilic OXA and hydrophobic RAPA were co-loaded using MPP and TPGS-based polymer capsules (i.e. TMOR), which were further coated by chitosan-modified gel to form TMOR-CDAN. The TMOR-CDAN displayed higher stability in both acidic and basic pH than free OXA and RAPA and could withstand the harsh gastric environmental conditions, preventing the burst drugs release while releasing the co-loaded drugs in a sustained and controlled manner. The dual-drug-loaded TMOR-CDAN provides a bifunctional platform for synergistic tumor therapy. Compared with the single drug OXA, RAPA, or the OXA and RAPA mixtures (OR), the TMOR-CDAN showed more outstanding in vitro cytotoxicity and in vivo antitumor chemotherapeutic efficacy, endowing the TMOR-CDAN with a prodigious potential for futuristic cancer chemotherapy .
研究领域:
药学
·
纳米技术
·
癌症研究
·
药物递送系统
✓ 已验证
产品关联
DOI
高影响因子
International Journal of Nanomedicine
·
2023
·
IF 8
Hao Wu,Qingxiang Zhong,Rongling Zhong,Houcai Huang,Zhi Xia,Zhongcheng Ke,Zhenhai Zhang,Jie Song,Xiaobin Jia
Oleanolic acid (OA) is a triterpenoid found in various fruits and vegetables and used in traditional Chinese medicine. OA plays a crucial role in the treatment of several cancers, but poor water solubility, low permeability, and significant efflux have limited its widespread clinical use. Vitamin E-d-α-tocopheryl polyethylene glycol succinate (vitamin E-TPGS) and Pluronic P105 were used to improve the solubility and permeability and to decrease the efflux of OA. OA-loaded mixed micelles were prepared by ethanol thin-film hydration. The physicochemical properties of the micelles, including zeta potential, morphology, particle size, solubility, drug loading, and drug entrapment efficiency were characterized. OA release from micelles was slower than that from the free drug system. OA uptake by A549 non-small-cell lung cancer (NSCLC) cells was enhanced by the micelles. A tumor model was established by injecting A549 cells into nude mice. In vivo imaging showed that OA-micelles could accumulate in the tumors of nude mice. Additionally, smaller tumor size and increased expression of pro-apoptotic proteins were observed in OA-micelle-treated mice, indicating that OA-micelles are more effective than free OA in treating cancer. In vitro experiments were performed using two NSCLC cell lines (A549 and PC-9). Cytotoxicity evaluations showed that the half-maximal inhibitory concentrations of free OA and OA-micelles were 36.8±4.8 and 20.9±3.7 μM, respectively, in A549 cells and 82.7±7.8 and 56.7±4.7 μM, respectively, in PC-9 cells. Apoptosis assays revealed that the apoptotic rate of OA-micelle-treated A549 and PC-9 cells was higher than that of cells treated with the same concentration of free OA. Wound healing and transwell assays showed that migration and invasion were significantly suppressed in OA-micelle-treated cells. Immunofluorescence and Western blot analyses confirmed that the epithelial–mesenchymal transition was reversed in OA-micelle-treated cells. Mixed micelles are a promising nano-drug delivery system for lung cancer treatment.
研究领域:
药学
·
癌症研究
·
药物递送系统
·
纳米技术
·
细胞生物学
✓ 已验证
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）