查找使用阿拉丁产品的科研文献

Preparation, characterization and in vitro study of bellidifolin nano-micelles

Fan Gao,Ziyue Chen,Li Zhou,Xuefeng Xiao,Lin Wang,Xingchao Liu,Chenggang Wang,Qiuhong Guo

Bellidifolin (BEL), a xanthone compound, has significant therapeutic effectiveness in cardiac diseases such as arrhythmias. However, BEL is limited in clinical applications by its hydrophobicity. In this work, we used BEL as the active pharmaceutical ingredient (API), and polyethylene glycol 15-hydroxy stearate (Kolliphor HS15) as the carrier to prepare BEL nano-micelles by a solvent-volatilization method. According to an analysis by differential scanning calorimetry (DSC), BEL was successfully encapsulated in HS15 as BEL nano-micelles with a 90% encapsulation rate, and particle size was 12.60 ± 0.074 nm in the shape of a sphere and electric potential was −4.76 ± 4.47 mV with good stability and sustained release characteristics. In addition, compared with free drugs, these nano-micelles can increase cellular uptake capacity, inhibit the proliferation of human cardiac fibroblasts, and down-regulate the expression of Smad-2, α-SMA, Collagen I, and Collagen III proteins in myocardial cells to improve myocardial fibrosis. In conclusion, the BEL nano-micelles can provide a new way for the theoretical basis for the clinical application of anti-cardiac fibrosis.

Multilamellar spherical micelles of alkali lignin: dissipative particle dynamics simulations

Zhu Guodian,Shang Jingqi,Wen Weihong,Li Yuanyuan,Yin Guoqiang

Context Lignin has an immense potential for the production of lignin-based functional materials. In this work, effect of 2-chloro-ethyltrimethyl ammonium chloride (AC)-grafted alkali lignin (AL) on the morphologies in water was investigated by dissipative particle dynamics (DPD) simulations. The results showed that AL molecules formed spherical micelles, but the corresponding phenylpropane units of AL were randomly distributed in spherical micelles. However, AC-grafted modification of phenolic hydroxyl groups in AL led to the formation of multilamellar spherical micelles. The formation of multilamellar spherical micelles of AL mainly went through four stages: small clusters, larger aggregates with a core-shell structure, trilaminar, and multilamellar spherical micelles. AL molecules resulted in dimethomorph molecules being randomly distributed in the spherical micelle, while the dimethomorph molecules were perfectly entrapped into the spherical micelles of AC-grafted AL. Various molecular weights of AL had no effect on the formation and size of multilamellar spherical micelles. With increasing the content of AC-grafted AL, small clusters, multilamellar spherical micelles, tube-like, and lamellar aggregates were observed successively. This work highlights the potential of lignin to prepare monodispersed lignin-based functional colloidal spheres. Methods Coarse-grained beads were performed energy minimization, geometric optimization, NPT ensemble (298 K and 1.0 bar), and NVT ensemble (298 K) calculations. DPD simulations were carried out at 300,000 steps in a 30×30×30 Rc 3 cubic box with Materials Studio 7.0 program.

Glucosamine-Modified Reduction-Responsive Polymeric Micelles for Liver Cancer Therapy

Lei Meng,Fangshu Liu,Chenchen Du,Jiaying Zhu,Qian Xiong,Jing Li,Weitong Sun

In this work, glucose transporter-1 (GLUT-1) and glutathione (GSH) over-expression in liver cancer was utilized to design a reduction-responsive and active targeting drug delivery system AG-PEG-SS-PCL (APSP) for the delivery of sorafenib (SF). The SF-APSP micelles were prepared using the thin film hydration method and characterized by various techniques. In vitro release experiments showed that the cumulative release of SF-APSP micelles in the simulated tumor microenvironment (pH 7.4 with GSH) reached 94.76 ± 1.78% at 48 h, while it was only 20.32 ± 1.67% in the normal physiological environment (pH 7.4 without GSH). The in vitro study revealed that glucosamine (AG) enhanced the antitumor effects of SF, and SF-APSP micelles inhibited proliferation by targeting HepG2 cells and suppressing cyclin D1 expression. The in vivo antitumor efficacy study further confirmed that the SF-APSP micelles had excellent antitumor effects and better tolerance against nude mouse with HepG2 cells than other treatment groups. All in all, these results indicated that SF-APSP micelles could be a promising drug delivery system for anti-hepatoma treatment.Keywords:liver cancer;glucosamine;sorafenib;reduction-responsive;polymer micelles

Ultrasound-responsive copolymeric micelles prepared by RAFT polymerization using a difunctional spiropyran-based RAFT agent: Investigation of mechanochromism kinetics, responsivities, and enhanced spiropyran mechanoactivation within micelles

Lijun Wang,Yangyang Zhang,Yanfei Wang,Shiding Zhang,Fang Wang,Haixiang Song,Hanyi Duan

An in-depth investigation of the ultrasonic response of mechanophores containing weak covalent bonds within nanosized aggregates is vital for ultrasound imaging, drug delivery, and sensors. In this work, well-defined amphiphilic block SP-[poly(methyl methacrylate- b -N-isopropylacrylamide)] 2 SP-[p(MMA- b -NIPAM)] 2 ( P1 ) and amphiphilic random, SP-[poly(methyl methacrylate- r -N-isopropylacrylamide)] 2 SP-[p(MMA- r -NIPAM)] 2 ( P2 ) copolymers with SP mechanophore embedded at midpoint polymer chain are prepared by RAFT (reversible addition-fragmentation chain transfer) polymerization using a pre-synthesized novel functional bi (trithiocarbonate) and spiropyran (SP)-based RAFT reagent. Both P1 and P2 copolymers self-assemble in spherical micelles in AcCN/water mixed solvents, and several assemblies with different water contents are fabricated. The structural differentiation between block P1 and random P2 dominates the inverse influence of water content on the aggregate sizes of micelles. Under ultrasound irradiation , the SP mechanophore is activated within both micelles, and the amount of activated SP mechanophore increases progressively with prolonged sonication time. For P1 , the mechanochemical reaction (mechanochromism) kinetics in an aggregated state and a single chain state are different, while that of P2 micelles and liner are similar, inferred to be associated with the structure difference between both micelles. The mechanoactivation of SP mechanophore within micelles in AcCN/water mixed solvents is higher than in dissolved state due to the micellization of P1 and P2 , entangling the hydrophobic PMMA segments and partially swelling in the micellar core. Moreover, an increase in the medium's dielectric constant around the core's SP is also observed, promoting the SP mechanoactivation. This approach may provide a new strategy for preparing novel mechanophore-centered amphiphilic copolymers with colorful structures and high hydrophilicity . These can self-aggregate into nanoparticles in aqueous or mixed solutions, exhibiting effective effects of ultrasonic responsiveness. We expect this work to push forward the in-depth studies on the ultrasonic responsive mechanism of assembly and help open new research avenues into the mechanochemical reactions within nanosized aggregates.

Enhanced Oral Delivery of Insulin via Loading in Polysorbate-80 Micelles

Rujing Xu,Ying Lu,Mengxiao Liu,Yanzhao Yin,Junsheng Zhao,Lin Wu,Song Shen

Oral delivery of insulin exhibits low bioavailability due to the hydrolysis in acidic gastric juice, biodegradation of enzymes, and inefficient penetration through the intestinal mucus and epithelial cell layer. Here, we report a micelle platform to enhance the oral delivery of insulin. Insulin was precipitated by zinc ions to form hydrophobic nanoparticles and subsequently coated with a surfactant polysorbate-80 (Tween-80) to form nanosized micelles (TW-Zn-rhINS). Tween-80 protects the insulin from the degradation of enzymes, meanwhile facilitating the diffusion within mucus and the epithelial cell layer by opening the tight junctions. The micelles were then lyophilized and encapsulated in enteric capsules to overcome acidic hydrolysis in gastric juice. The micelles significantly increased transcellular insulin transport and uptake. The in vivo experiments demonstrated that oral TW-Zn-rhINS micelle capsules (30 IU/kg) decreased the blood glucose of diabetic mice by 58.74% after administration for 6 h, while the postprandial blood glucose dropped by 51.1%. Pharmacokinetics data indicated that the relative oral bioavailability of TW-Zn-rhINS was 7.88%, which was 7.73 times higher than that of insulin. The micelles present a promising platform to enhance the oral bioavailability of insulin, also indicating a potential for oral delivery of protein.

Branched Mesoporous TiO2 Mesocrystals by Epitaxial Assembly of Micelles for Photocatalysis

Pengfei Zhang,Zhangliu Tian,Chin-Te Hung,Yong Liu,Bingquan Jia,Kun Lan,Biao Kong,Fuqiang Huang,Liqiang Mai,Dongyuan Zhao

The understanding and control of the structural complexity of mesoporous semiconductors with single-crystal-like nature are both attractive and challenging. Here, we report a crystallization-driven epitaxial assembly from monomicelles to construct branched mesoporous TiO 2 mesocrystals (m-TiO 2 MCs) with coherent atomic domains. The star-shaped multipods are obtained by two-step evaporation with nanocrystal mediation, primarily consisting of arms along < 001 >, < 101 >, and < 111 > crystal directions. For each arm, ordered open mesochannels arrange in parallel along the growth direction. The m-TiO 2 MC multipods have a surface area of ∼116 m 2 /g and single-crystal-like frameworks and are good hydrogen evolution photocatalysts. Under full-spectrum irradiation, the branched m-TiO 2 MCs exhibit a hydrogen evolution rate of 8 mmol h −1 g −1 , which is more than four times higher than that of commercial TiO 2 P25. This crystallization-driven self-assembly approach may provide valuable insight into designing programmable mesoporous mesocrystals by controlling the oriented assembly of monomicelle building blocks.

mPEGylated solanesol micelles as redox-responsive nanocarriers with synergistic anticancer effect

Benkai Qin,Lei Liu,Xiaohe Wu,Fengguang Liang,Tian Hou,Yangyang Pan,Shiyong Song

We prepared an amphiphilic redox-responsive conjugate based on mPEGylated solanesol, solanesyl poly(ethylene glycol) dithiodipropionate (SPDP), along with its inert counterpart solanesyl poly(ethylene glycol) succinate (SPGS), which self-assembled in aqueous solution to form redox-responsive micelles . Used as efficient drug carriers for doxorubicin (DOX), the micelles acted as synergistic agents for cancer therapy. Dynamic light scattering (DLS) measurements showed that the SPDP micelles had average diameters of 111   nm, which decreased to 88   nm after the encapsulation of DOX. The mean diameters and size distribution of the disulfide-containing micelles changed obviously in the presence of the reducing agent glutathione (GSH), whereas no changes occurred in the case of redox-insensitive SPGS micelles. DOX could be loaded into both types of micelles, with drug loading content of about 4.0%. A significantly accelerated release of DOX was triggered by GSH for DOX-loaded SPDP micelles, compared with DOX-loaded SPGS micelles. Blank SPGS and SPDP micelles displayed higher inhibition of HeLa and MCF-7 cell proliferation but less cytotoxicity to normal L-02 cells at similar concentrations. Confocal microscopic observation indicated that a greater amount of DOX was delivered into the nuclei of cells following 9 or 12   h incubation with DOX-loaded micelles. In vivo studies on H22-bearing Swiss mice demonstrated the superior anticancer activity of DOX-loaded SPDP micelles over free DOX and DOX-loaded SPGS micelles. All of the data presented here suggested that these SPDP micelles may have a dual function, as they are preferentially toxic for tumor cells alone and are efficient and safe carriers for anticancer drugs. Statement of Significance Various nanoscale drug carriers were used to enhance therapeutic effect of many drugs. While, the metabolites of high quantities of carriers may cause additional short- or long-term toxicities. In this study, a new systems based on solanesol derivatives was developed for anticancer drug delivery. There are two features for this system. One is solanesol originated bioactivity of the carrier, which will synergistically facilitate therapeutic effect of the encapsulated drug. The other is the redox-responsive drug release behavior adaptable to the glutathione-rich atmosphere of tumor cell. All the hypothesis have been elucidated in this work through in vitro and in vivo studies. It was found that this drug delivery system may have a dual function, as they are preferentially toxic for tumor cells alone and are efficient and safe carriers for anticancer drugs.

From small deferiprone to macromolecular micelles: Self-assembly enhances iron chelation

Xiaoli Huang,Di Lu,Yongmin Ma,Limei Zhang,Lina Wang,Jian Deng,Zheng Wang,Yanjun Zhao

We report a self-assembly-based approach for improved iron chelation of small chelators. A model chelator, deferiprone (DFP) is covalently linked to amphiphilic poly(ethylene glycol)-polypeptide block copolymer that can assemble into micelles . The free DFP generally coordinates with iron in a ratiometric manner (3:1). However, the assembly induces DFP packing in the micelle cores, which restricts its conformational freedom. Hence DFP/iron coordination ratio in micelles is reduced (< 3:1), which leads to an enhanced chelation performance of DFP. In addition, the micellar nanocarrier usually exhibits an extended systemic circulation in contrast to the free DFP. The current work opens new avenues for developing novel nanomedicines for iron overload diseases.

Smart pH-responsive polymeric micelles for programmed oral delivery of insulin

Wen Yao Hu,Zhi Min Wu,Qian Qian Yang,Yue Jin Liu,Juan Li,Can Yang Zhang

The development of intelligent oral drug delivery carrier aiming at efficiently bring insulin to intestine is of great significance for diabetes mellitus therapy. In the present study, a series of amphiphilic pH-sensitive block copolymer poly(methyl methacrylate- co -methacrylicacid)- b -poly(2-amino ethyl methacrylate) [P(MMA- co -MAA)- b -PAEMA] was synthesized via activators regenerated by electron transfer atom transfer radical polymerization (ARGET ATRP) and further self-assembled into pH-responsive cationic polymeric micelles (PCPMs) for oral insulin delivery. The structure and molecular weight were confirmed by proton nuclear magnetic resonance ( 1 H-NMR), Fourier transforming infrared spectrum (FT-IR) and gel permeation chromatography (GPC), respectively. The critical micelle concentration (CMC) values of these copolymers were measured by fluorescent probe method at pH 1.2 (8–15 μg/mL) and pH 7.4 (22–42 μg/mL), respectively, demonstrating high stability at acidic environment. A decrease in the particle size of PCPMs was associated with an increased pH at beginning, which reached around 200 nm at neutral pH, while the particle size increased obviously with pH increase, indicating the pH-sensitivity of PCPMs. The insulin was entrapped into the core of PCPMs (Ins-loaded PCPMs) with high loading efficiency via diafiltration method. The in vitro experiments show Ins-loaded PCPMs have low toxicity and exhibit pH-triggered release profile with remitted initial burst release. The results indicate that the PCPMs self-assembled from P(MMA- co -MAA)- b -PAEMA may be potential carriers for efficient oral delivery of insulin with controlled release property.

RETRACTED ARTICLE: Bicomponent polymeric micelles for pH-controlled delivery of doxorubicin

Chunyun Wang,Peilan Qi,Yan Lu,Lei Liu,Yanan Zhang,Qianli Sheng,Tianshun Wang,Mengying Zhang,Rui Wang,Shiyong Song

The Editors and Publisher of the journal Drug Delivery, have retracted the following article:Chunyun Wang, Peilan Qi, Yan Lu, Lei Liu, Yanan Zhang, Qianli Sheng, Tianshun Wang, Mengying Zhang, Rui Wang & Shiyong Song (2020) Bicomponent polymeric micelles for pH-controlled delivery of doxorubicin, Drug Delivery, 27:1, 344–357, DOI: 10.1080/10717544.2020.1726526Since publication, concerns have been raised about the integrity of the data in the article. When approached for an explanation, the authors have been unable to fully address the concerns raised. As verifying the validity of published work is core to the integrity of the scholarly record, we are therefore retracting the article. All authors listed in this publication have been informed.We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines.The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as ‘Retracted’.

Physical characterization and antioxidant activity of thymol solubilized Tween 80 micelles

Deng Ling-Li,Taxipalati Maierhaba,Que Fei,Zhang Hui

Attempts were made to solubilize thymol in Tween 80 micelle to study the solubilization mechanism of thymol and the effect of solubilization on its antioxidant activity. The maximum solubilized concentration of thymol in a 2.0% (w/v) Tween 80 micelle solution is 0.2 wt%. There was no significant difference in Z-average diameter between the empty micelles and thymol solubilized micelles. 1 H NMR spectra indicated that 3-H and 4-H on the benzene ring of thymol interacted with the ester group between the hydrophilic head group and the hydrophobic tail group of Tween 80 by Van der Waals’ force. Ferric reducing antioxidant potential (FRAP) and cupric ion reducing antioxidant capacity (CUPRAC) assays showed that the reducing antioxidant activity of free thymol did not change after solubilized in Tween 80 micelles. Compared to free thymol, the solubilized thymol showed higher activities to scavenge DPPH (2,2-diphenyl-1-picrylhydrazyl) and hydroxyl radicals. The present study suggested a possible preparation of thymol-carrying micelles with enhanced antioxidant activities that could be applied in food beverages.

Specific Disassembly of Lamellar Crystalline Micelles of Block Copolymer into Cylinders

Xiang-Yue Wang,Rui-Yang Wang,Bin Fan,Jun-Ting Xu,Bin-Yang Du,Zhi-Qiang Fan