EUROPEAN JOURNAL OF PHARMACOLOGY
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2022
·
IF 5.195
Bin Du,Mengmeng Zhao,Yuehua Wang,Lili Yu,Qingqing Jiao,Yimeng Bai,Genyang Cheng
The oxidative stress and activation of the fibrosis pathway are essential pathological mechanisms of acute kidney injury (AKI). In this article, we designed a drug delivery system that could effectively improve oxidative stress and relieve fibrosis by the combination of precise targeting, solubilization, and reducing the toxicity of nano-transport system to strengthen the efficacy of AKI. Folic acid (FA) was used as the targeting molecule, and curcumin (Cur) and resveratrol (Res), which are Chinese medicine monomers with anti-inflammatory and antioxidant effects, were used as model drugs. Here, the targeting nanosystem (Cur/ [email protected] /TPGS) co-loaded with Cur and Res was successfully synthesized. Finally, the comprehensive therapeutic effect of the nanosystem was evaluated through the targeted and pharmacodynamic researches on the AKI models induced by cisplatin (CDDP) in vitro and in vivo . The studies in vitro proved that the nanosystem could not only specifically target HK-2 cells and promote the effective accumulation of Cur and Res in the kidney, but also effectively improve oxidative stress by eliminating reactive oxygen species (ROS), stabilizing mitochondrial membrane potential (MMP), and reducing the expression of apoptosis-related proteins. The studies in vivo showed that the nanosystem could effectively play the role of anti-oxidation, anti-inflammatory and alleviate fibrosis to reduce the apoptosis and necrosis of renal tubular cells. The nanosystem could coordinately repair damaged HK-2 cells by improving oxidative stress, inhibiting inflammation and tissue fibrosis, which provided a new idea for the treatment of AKI.
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TOXICOLOGY AND APPLIED PHARMACOLOGY
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2022
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IF 4.46
Mengxue Pang,Songchao Duan,Mengmeng Zhao,Qingqing Jiao,Yimeng Bai,Lili Yu,Bin Du,Genyang Cheng
To treat acute kidney injury with high efficiency and low toxicity, a novel nanoplatform was developed to remove excess reactive oxygen species (ROS). Lutein (LU) and celastrol (Cel) were loaded into low molecular weight chitosan (CS) to prepare [email protected] nanomicelles . Renal tubular epithelial (HK−2) cell uptake experiments showed that the drugs could be internalized in renal tubular via the megalin receptor. In this study, the amide bond formed by the reaction of citraconic anhydride (CA) with an amino group of CS could be destroyed under acidic conditions. Therefore, the drugs were released in HK-2 cells due to the acidic environment of the lysosome . In vitro studies showed that the nanomicelles could reduce toxicity in non-target organs and enhance therapeutic efficacy in acute kidney injury (AKI). In addition, [email protected] micelles had alleviated kidney oxidative stress disorder and stabilized the mitochondrial membrane potential quickly. Next, in vivo studies proved that [email protected] micelles could inhibit the activation of the NF-κB p65 and p38 MAPK inflammatory signaling pathways. Therefore, the micelles further reduced the overexpression of related inflammatory factors. In conclusion, [email protected] nanomicelles could treat AKI with high efficiency and low toxicity, and inhibit renal fibrosis .
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COLLOIDS AND SURFACES B-BIOINTERFACES
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2021
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IF 5.268
Baohuan Wu,Sixiang Sai,Keke Li,Xingchen Sun,Jingtian Han,Baocheng Tian
Drugs that are topically applied on the eyes have low bioavailability, which has always been an important problem. In this study, maleimide functionalized, voriconazole (VCZ) loaded mixed micelles (Mal-VCZ-MM) were designed. Pluronic F127 and phospholipid were used as materials, and maleimide was used as an adhesive. The prepared Mal-VCZ-MM was nearly spherical with a particle size of 84.45 ± 1.39 nm and a zeta potential of − 20.3 ± 0.29 mV. The encapsulation efficiency of Mal-VCZ-MM was 95.33 ± 0.06%, and it had high stability with a critical micelle concentration value of 1.28 × 10 -4 mg/mL. CCK-8 assay showed that its cytotoxicity was lower than that of free VCZ solution (VCZ-Sol). Both quantitative and qualitative analyses of the HCE-T cellular uptake showed that the cellular internalization of Mal-C6-MM was significantly stronger than that of C6-MM. The endocytosis pathway was macropinocytosis-mediated, cavernous-mediated, and energy-dependent. In vitro results against Candida albicans showed that the diameters of the antifungal inhibition zones of VCZ-Sol, VCZ-MM, and Mal-VCZ-MM were 15.5 ± 0.50 mm, 24.0 ± 0.71 mm, and 31.5 ± 1.12 mm, respectively. The antifungal effect of Mal-VCZ-MM was significantly higher than that of VCZ-Sol and VCZ-MM ( P < 0.001). This study shows that Mal-VCZ-MM is a highly effective hydrophobic ophthalmic drug-delivery carrier that can improve the therapeutic effect of the drug.
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RSC Advances
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2016
·Vol. 6
·期 11
·9164-9174
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IF 3.289
Mingjia Chen,Chunmei Gao,Shaoyu Lü,Yuanmou Chen,Mingzhu Liu
At present, diselenide bonds have been considered as a novel dual redox-sensitive linkage. Nevertheless, few studies have focused on diselenide-linked polysaccharide as new biological materials. In this work, the diselenide-linked mPEGylated starch amphiphilic copolymers (mPEG-SeSe-St), which combined the biocompatibility of polysaccharide and the stimuli-responsiveness of diselenide linkages, were developed as a novel type of PEG-detachable drug vector for rapid drug release. The amphiphilic design of the mPEG-SeSe-St enabled the formation of self-assembled micelles with spherical core–shell structures in aqueous solution. The data of well-ordered appraisals demonstrated that mPEG-SeSe-St could be disrupted in the presence of a low concentration of hydrogen peroxide (H2O2, 0.1% (v/v)) or glutathione (GSH, 1 mM). The process of diselenide bonds' more rapid degradation than disulfide bonds led to a synergistically enhanced release of loaded anticancer drugs (DOX) in cellular environments. These results, combined with cell viability measurements and confocal laser scanning microscopy (CLSM), indicated that mPEG-SeSe-St micelles might have appeared as a refined platform for cancer therapy.
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RSC Advances
·
2012
·Vol. 2
·期 31
·11953-11962
·
IF 0
Dali Wang,Xiuying Huan,Lijuan Zhu,Jinyao Liu,Feng Qiu,Deyue Yan,Xinyuan Zhu
A new type of salt/pH dual-responsive micelles based on supramolecular amphiphilic brush copolymers, poly(2-hydroxyethyl metharylate)-g-(poly(ε-caprolactone)-adenine:uracil-poly(ethylene glycol)) (PHEMA-g-(PCL-A:U-PEG)) was developed for the anticancer drug delivery owing to the fact that the tumor tissues show low pH and high salt concentration. The supramolecular structure of brush copolymer was confirmed by variable-temperature 1H NMR and Fourier transform infrared spectroscopy (FTIR). Doxorubicin (DOX) as a model anticancer drug was efficiently loaded into the supramolecular micelles (up to 70%) due to the compact structure of brush polymer. The cumulative release profile of the DOX-loaded micelles showed a low level of drug release (about 20 wt% in 25 h) at pH 7.4 with a low salt concentration, and was significantly accelerated at a lower pH (5.0) and a high salt concentration (over 70 wt% in 6 h), exhibiting an salt/pH dual-responsive controlled drug release capability. Methyl tetrazolium (MTT) assay showed that DOX-loaded micelles had high anticancer efficacy against Hela cancer cells and blank micelles had a very low cytotoxicity. These supramolecular brush copolymer micelles possess many favorable traits, such as low cytotoxicity and excellent biodegradability, adequate drug loading capacity, and rapid drug release in response to the intracellular level of pH and salt concentration, which endow them as a promise candidate for delivering anticancer drugs.
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JOURNAL OF MICROENCAPSULATION
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2021
·
IF 3.142
Zhumei Ge,Qilong Wang,Qin Zhu,Mukhtar Yusif,Jiangnan Yu,Ximing Xu
Herein, a nano-micelle drug delivery system was developed to orally improved zingerone’s bioavailability and its antitumor effect. Indeed, zingerone-loaded d-α-tocopheryl polyethylene glycol succinate micelles (ZTMs) were effectively prepared, characterised and assessed. The ZTMs had diameter, polydispersity index, and zeta potential of 50.62 ± 0.25 nm, 0.168 ± 0.006, and −28.07 ± 0.33 mV, respectively, coupled with a high entrapment efficiency (m/m, %) were 94.71 ± 2.02. The release rate of ZTMs in three media was significantly greater than that of free zingerone. Intriguingly, results obtained from pharmacokinetic studies showed that the oral bioavailability of the ZTMs was enhanced by 5.10 times in comparison with the free zingerone. Further, the half inhibitory concentration (IC50) of ZTMs and free zingerone was 7.56 μg/ml and 14.30 μg/ml, respectively, on HepG2 cells. Hence, ZTMs may be used as a potential approach to enrich the solubility, bioavailability, and concomitant anti-proliferative effect of zingerone in vitro.
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高影响因子
MOLECULES
·
2019
·Vol. 24
·期 24
·4508
·
IF 3.06
Jing Wang,Xu Xu,Hao Chen,Shuai-Shuai Zhang,Yin-Xian Peng
Au nanoparticles (NPs) were prepared by UV light irradiation of a mixed solution of HAuCl4and sodium deoxycholate (NaDC) under alkaline condition, in which NaDC served as both reducing agent and capping agent. The reaction was monitored by circular dichroism (CD) spectra, and it was found that the formed gold NPs could catalyze the oxidation of NaDC. A CD signal at ~283 nm in the UV region was observed for the oxidation product of NaDC. The intensity of the CD signal of the oxidation product was enhanced gradually with the reaction time. Electrospray ionization (ESI) mass spectra and nuclear magnetic resonance (NMR) spectra were carried out to determine the chemical composition of the oxidation product, revealing that NaDC was selectively oxidized to sodium 3-keto-12-hydroxy-cholanate (3-KHC). The chiral discrimination abilities of the micelles of NaDC and its oxidation product, 3-KHC, were investigated by using chiral model moleculesR,S-1,1′-Binaphthyl-2,2′-diyl hydrogenphosphate (R,S-BNDHP). Compared with NaDC, the micelles of 3-KHC displayed higher binding ability to the chiral model molecules. In addition, the difference in binding affinity of 3-KHC micelles towardsR,S-isomer was observed, andS-isomer was shown to preferentially bind to the micelles.Keywords:noble metal nanoparticles;catalytical oxidation;chiral recognition;bile salts;supramolecular chemistry
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BIOMATERIALS
·
2014
·
IF 8.312
Wantong Song,Zhaohui Tang,Dawei Zhang,Ying Zhang,Haiyang Yu,Mingqiang Li,Shixian Lv,Hai Sun,Mingxiao Deng,Xuesi Chen
There are two important obstacles for the currently applied anti-cancer drug delivery systems. One is the conflict between long-circulation and cellular uptake while the other one is the achievement of ideal anti-cancer efficacy. To solve these problems, we designed a polypeptide-based micelle system that combined the advantages of receptor mediated endocytosis and multi-drug delivery. Firstly, an amphiphilic PLG- g -Ve/PEG graft copolymer was prepared by grafting α-tocopherol (Ve) and polyethylene glycol (PEG) to poly( l -glutamic acid) (PLG). Then docetaxel (DTX) and cisplatin (CDDP) were co-loaded into the PLG- g -Ve/PEG micelles via hydrophobic and chelation effect. After that, the surface of the dual-drug-loaded micelles was decorated with an α v β 3 integrin targeting peptide c(RGDfK). The targeted dual-drug-loaded micelles showed synergistic cytotoxicity and enhanced internalization rate in mouse melanoma (B16F1) cells. In vivo tests demonstrated that remarkable long circulation, anti-tumor and anti-metastasis efficacy could be achieved using this drug delivery system. This work revealed a strategy for the design and preparation of anti-cancer drug delivery systems with reduced side effect, enhanced anti-tumor and anti-metastasis efficacy.
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JOURNAL OF NANOPARTICLE RESEARCH
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2022
·Vol. 24
·期 6
·1-16
·
IF 2.533
Yang Yuhang,Zhu Zhongan,Adu-Frimpong Michael,Liu Jing,Wang Yaping,Chen Lin,Toreniyazov Elmurat,Ji Hao,Cao Xia,Shi Feng,Wang Qilong,Yu Jiangnan,Xu Ximing
Licorice chalcone A (LCA) possesses a variety of pharmacological activities amid poor solubility in water which consequently restricts its clinical application. In this study, LCA micelles (LCA-M) and LCA micelles modified with TPGS (LCA-M-T) were prepared, wherein in vitro, in vivo, and hepatoprotection potential of the formulations were evaluated. LCA-M-T and LCA-M were prepared by thin-film dispersion method and characterized by a transmission electron microscope (TEM). The encapsulation efficiency, in vitro release, and stability of LCA-M-T and LCA-M were detected by HPLC and UV, respectively. The pharmacokinetics, tissue distribution studies, and pharmacodynamics research were also carried out after oral administration. The sizes of micellar particles were 34.02 ± 0.29 nm (LCA-M) and 62.46 ± 0.51 nm (LCA-M-T) with 0.223 ± 0.021 (LCA-M) and 0.343 ± 0.006 (LCA-M-T) polydispersities, − 35.06 ± 2.27 mV (LCA-M) and − 38.58 ± 1.69 mV (LCA-M-T) zeta potentials, and 95.2 ± 0.27% (LCA-M) and 90.34 ± 0.31% (LCA-M-T) encapsulation efficiencies. The drug loadings were 8.56 ± 0.27% (LCA-M) and 8.04 ± 0.19% (LCA-M-T). The two preparations released quickly and reached over 95% in the four-dissolution media (pH = 1.2 pH = 6.8 pH = 7 pH = 7.4). The preparations of LCA showed significant elevation of cumulative release compared with the free LCA and more importantly 119% (LCA-M) and 285% (LCA-M-T) increments in the relative oral bioavailability of the drug. Preparations of LCA may act as a promising approach to improve solubility and enhance bioavailability and liver protective activity of LCA.
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JOURNAL OF APPLIED POLYMER SCIENCE
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2026
·
IF 2.8
Menglu An,Jingbo Li,Shaokui Cao,Yingliang Liu,Jingguo Li,Jun Shi
Casein-based nanocarriers have demonstrated significant potential in drug delivery due to their excellent biocompatibility, amphiphilic nature, and pH responsiveness. However, casein-based drug carriers suffer from the problems of single intelligent response and poor controllability of drug release. In this study, casein was combined with hollow copper sulfide (CuS) nanoparticles with near-infrared (NIR) responsiveness through electrostatic self-assembly interaction to generate CuS@casein micelles (CuS@CM) with sustained and pH/NIR dual-responsive drug release properties. The strong negative charge of casein and the hollow structure of CuS ensure a high doxorubicin (DOX) loading efficiency (96.84%) of CuS@CM. Ca 2+ is bound with casein to form inter-casein calcium bridges, thereby providing significant sustained release properties for CuS@CM. The charge inversion property of casein at different pH values and excellent NIR responsiveness of hollow CuS nanoparticles endows CuS@CM with superior pH/NIR dual-responsive drug release performance. In vitro cell viability results demonstrated that the pH/NIR dual-responsiveness of CuS@CM-DOX, as well as its excellent tumor cellular uptake capability, could effectively induce tumor cell death. Overall, this study generates a novel casein-based nanocarrier with sustained and pH/NIR dual-responsive drug delivery properties, which has potential application in the field of tumor-targeted drug delivery.
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产品关联
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高影响因子
International Journal of Pharmaceutics-X
·
2026
·
IF 6.4
Xu Luo,Ziqiong Yang,Jianqiu Chen,Mengqi Shen,Kun Wang,Qian Du
Colorectal cancer chemotherapy faces challenges with low intratumoral drug accumulation and off-target toxicity. Micellar liposome complex carriers are a promising anti-cancer platform due to their high encapsulation efficiency, responsive release, and multi-targeting capabilities. This study explores a novel tumor-targeted chemotherapy approach by encapsulating GSH/NQO1-responsive SN38 prodrug micelles into cholesterol-replacement multifunctional liposomes. Timosaponin AIII (TAIII), a steroid saponin with anticancer activity, substitutes cholesterol to stabilize liposomes, benefiting from its steroidal aglycone structure. Additionally, TAIII mimics PEGylation via its glucose moiety, enhancing tumor targeting via the overexpression of glucose transporter 1 (GLUT1) on cancer cells. Molecular docking studies with AutoDock revealed that GLUT1 residues stabilize TAIII in the binding pocket through hydrogen bonding, hydrophobic, and polar interactions, promoting its transmembrane transport. A specific amphiphilic SN38 prodrug, PEG-SS-SN38-QPA (PSSQ), was synthesized and self-assembled into micelles via a solvent injection-dialysis method for GSH/NQO1-responsive controlled drug release in the tumor microenvironment. PSSQ micelles were integrated into the hydrophilic cavity of TAIII-based liposomes (TLP, prepared by the thin-film hydration method) through passive encapsulation to form PSSQ@TLP. In vitro release study exhibiting GSH/NQO1-triggered release under simulated tumor microenvironment. In vitro cytotoxicity evaluation was performed using the MTT assay on HCT116, LOVO, CT26.WT cell lines. Following in vivo evaluations of biodistribution, anti-tumor efficacy, and biosafety in CT26.WT xenograft tumor-bearing mice, PSSQ@TLP demonstrated enhanced intratumoral accumulation, robust tumor suppression, and minimized systemic toxicity, underscoring its promise as a targeted therapeutic strategy for colorectal cancer.
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高影响因子
Frontiers in Bioengineering and Biotechnology
·
2021
·
IF 5.89
Yu Juan,Xu Chaoqun,Lu Chuanwei,Liu Qian,Wang Jifu,Chu Fuxiang
Preparation and application of sustainable polymers derived from renewable resources are of great significance. The aim of this study is to synthesize a kind of sustainable polymeric micelles from rosin and vegetable oils via atom transfer radical polymerization (ATRP) and to investigate the doxorubicin delivery properties of these micelles. Dehydroabietic acid–based poly lauryl methacrylate (DA-PLMA) with narrow PDI of 1.13 was prepared in a well-controlled process using rosin as an ATRP initiator. Thereafter, carboxylic groups were introduced to form poly methacrylic acid (PMAA) moieties in DA-PLMA polymer via acid hydrolysis. The resulted DA-PLMA-PMAA could self-assemble in water to form pH-dependent polymeric micelles with a diameter of ∼65 nm and PDI as low as 0.105. Owing to the existence of rosin, DA-PLMA-PMAA micelles also showed self-fluorescence properties. In addition, Dox-loaded micelles were prepared in aqueous solution with the drug-loading capacity as high as 16.0% and showed sustained-release characteristics. These results demonstrate great promise for designing polymeric micellar from rosin and vegetable oils.
研究领域:
材料科学
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生物医学工程
·
药剂学
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