查找使用阿拉丁产品的科研文献

Synthesis, fabrication and properties research of CS-mPEG-AN nanocomposite

KangRui Wang,Hong Tang,Hongjie Chen,Xiaorong Huang,Ying Fang,Rongrong Men,Jie Gao,Yue Wang,Yang Wang,ChengHong Huang

Smart drug carrier based on polyurethane material for enhanced and controlled DOX release triggered by redox stimulus

Chao Yu,Xing Tan,Zhenzhu Xu,Guodian Zhu,Wenqi Teng,Qingzhen Zhao,Zhong Liang,Zhimin Wu,Di Xiong

A series of amphiphilic polymer mPEG-PUSS-mPEG were developed by a combination of ring opening polymerization (ROP) and polyaddition reaction and its self-assembled micelles were developed for hydrophobic anticancer drugs delivery. Polymeric critical micellar concentration (CMC) values in aqueous solution were about 2.8–5.5 mg/L. And the partition equilibrium constant ( K v ) of pyrene in micellar solutions ranged from 1.52 × 10 5 to 2.20 × 10 5 . The average sizes of the self-assembled blank and DOX-loaded micelles were 160–180 nm determined by dynamic light scattering (DLS). The morphology of the DOX-loaded micelles was spherical by transmission electron microscopy (TEM) and scanning electron microscopy (SEM).The in vitro drug release behaviors of DOX and PTX from mPEG-PUSS-mPEG micelles were investigated at different simulated conditions. We found that the PTX release was significantly accelerated by redox stimuli compared with DOX-loaded reduction-sensitive PU micelles. The change of the size of this system under different conditions was further evaluated by DLS. DOX-loaded mPEG-PUSS-mPEG micelles in 50% fetal bovine serum (FBS) were evaluated the hemocompatibility. In addition, the self-assembly process of polymers mPEG-PUSS-mPEG in aqueous solution for micellar formation was also investigated by means of dissipative particle dynamics (DPD) simulations.AndCCK-8 assays revealed that the mPEG-PUSS-mPEG materials had low toxicity, but the DOX-loaded micelles showed a high cytotoxicity against HepG2 tumor cells. All results demonstrate that mPEG-PUSS-mPEG self-assembled micelles are a very promising for hydrophobic anticancer drugs delivery.

Linolenic acid-modified MPEG-PEI micelles for encapsulation of amphotericin B

Hongmei Xu,Fangfang Teng,Feilong Zhou,Li Zhu,Yi Wen,Runliang Feng,Zhimei Song

Aim: To encapsulate amphotericin B (AmB) with reduced toxicity and comparable activity. Results & methodology: The α-linolenic acid (ALA)-modified monomethoxy polyethylene glycol-g-PEI-g-ALA conjugate was employed to prepare AmB-loaded micelles (AmB-M). In vitro activity and release behavior of AmB-M were investigated. AmB-M enhanced AmB's water-solubility to 1.2 mg/ml, showing good storage stability. AmB-M could achieve a sustained and slow release of AmB, low hemolysis activity and negligible kidney toxicity when compared with commercial AmB injection. Antifungal activity and biofilm inhibition experiments confirmed that the antifungal activity of AmB-M against Candida albicans was similar to that of AmB injection. Conclusion: Monomethoxy polyethylene glycol-g-PEI-g-ALA micelles could be a preferable choice to treat systemic fungal infections as an efficient drug delivery system.

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.

Glucose-Responsive Microspheres as a Smart Drug Delivery System for Controlled Release of Insulin

Yu Jiaojiao,Wang Qiongyan,Liu Haofan,Shan Xiaosong,Pang Ziyan,Song Pengjin,Niu Feng,Hu Liandong

Background and Objectives Diabetes mellitus, a disease of glucose regulation, has become one of the most common medical problems in the world. At present, alternative therapy for diabetes has, to a large extent, been widely concerned with the improvement of treatment efficacy. The aims of this study were to characterize and evaluate the surface morphology of the novel glucose-responsive injectable microspheres containing insulin, along with their in vitro release and in vivo efficacy. Methods In this study, glucose-responsive microspheres as an emerging smart drug delivery system for controlled release of insulin were developed by an improved water-in-oil-in-water (W/O/W) double emulsion preparation method. Here, methoxypolyethylene glycol-hydrazone-4-methoxypolyethylene glycol benzoate (mPEG-Hz-mPEG4AB) was synthesized as a pH-responsive carrier. Results The microspheres had a good spherical structure with a particle size of 5 ~ 10 μm. Approximately 61% of insulin was released in 15 h under a high glucose environment but was barely released within the normal glucose range in in vitro studies. After a subcutaneous injection of insulin microspheres in rats, blood glucose levels rapidly decreased within 2 h and could be maintained for 2 days in the normal range. Histopathological evaluation indicated that the microspheres were almost non-irritating. Conclusions The pH-responsive mPEG-Hz-mPEG4AB could be used as an efficient insulin microsphere carrier, and the optimized microspheres had good morphology and sustained hypoglycemic effect.

Antibacterial efficacy and pharmacokinetics of a poly(mPEG-b-PCEA)–trimethoprim conjugate

Ming Niu,Zhenghua Zhang,Rourou Wang,Yaxin Zhou,Jing Zhou,Lumei Pu,Weibing Xu

Research into antimicrobials is crucial for the sustainable development of the livestock industry. Trimethoprim (TMP) is one of the most widely used antimicrobial agents in the world. However, its efficacy is often limited by poor water solubility and dose-limiting properties. In this work, amphiphilic block polymer carriers are prepared using the oxygen-induced reversible addition–fragmentation chain transfer polymerization reaction. TMP is linked to carriers in different ratios to form poly(mPEG-b-PCEA)–TPM conjugates. The conjugates are characterized using various methods including 1H NMR, FT-IR, XRD and SEM. The results of in vitro antimicrobial experiments show that poly(mPEG-b-PCEA)–TMP with different ratios has more prominent antimicrobial effects than the same dosage of pure TMP. poly(mPEG-b-PCEA)–TMP80 shows the most significant results, inhibiting E. coli by 87.19% and S. aureus by 97.02%, with a hemolysis rate of <5% and good biocompatibility. In vivo pharmacokinetics show an increase in Cmax from 4.81 μg mL−1 to 6.57 μg mL−1 and AUC0–48 from 78.55 h μg mL−1 to 89.11 h μg mL−1 for poly(mPEG-b-PCEA)–TMP80 compared to commercially available TMP tablets. This strategy can effectively improve the antibacterial activity and pharmacokinetics and increase the bioavailability of TMP.

ICG/MnO2-HFn-mPEG-DSPE-Lip enhances the anticancer activity of ICG phototherapy

Ma Dan,Lu Huixiang,Zhang Hai,Liao Anru,Peng Qianrong,Yang Min

Hypoxia poses a significant challenge to the efficacy of photodynamic therapy (PDT) for cancer treatment. This study aims to design and synthesize PEGylated liposomes encapsulating MnO₂, indocyanine green (ICG), and H-chain ferritin (HFn) to potentially address hypoxia and enhance the therapeutic outcomes of PDT. PEGylated liposomes (ICG/MnO₂-HFn-mPEG-DSPE-Lip) were constructed with a rod-like structure, incorporating MnO₂ as a hypoxia-modulating agent and ICG as a photosensitizer. The drug loading capacity, stability and safety of liposomes were characterized. Singlet oxygen quantum yield (Φ Δ ) was measured under simulated tumor microenvironment conditions. In vitro phototoxicity was evaluated using A549 human lung adenocarcinoma cells. Liposomes have a high drug loading capacity, good biocompatibility and good long-term stability. Under tumor-simulated conditions, Φ Δ was significantly improved, increasing from 0.210 for free ICG to 0.507. The liposomes demonstrated remarkable phototoxic effects on A549 cells (90.5% cell death under combined PDT/PTT vs. 15% for free ICG). This nanoplatform proposes a novel strategy to overcome hypoxia-induced PDT resistance, and the enhanced efficacy may be attributed to the increased oxygen supply mediated by MnO 2 carried by HFn. These findings provide important insights for the development of next-generation therapeutic systems targeting tumor hypoxia.

Injectable supramolecular hydrogels via inclusion complexation of mPEG-grafted copolyglutamate with α-cyclodextrin

Wu Lian-ying,Yu Lei,Fu Xiao-hui,Li Zhi-bo

A series of monomethoxy poly(ethylene glycol) (mPEG) grafted copolyglutamates (PmPEGs) were synthesized through ring-opening polymerization (ROP) followed by click chemistry. Supramolecular hydrogels based on polymer inclusion complexes (ICs) between PmPEG and α -cyclodextrin ( α -CD) were prepared in aqueous solution. The rheological measurements indicated their gelation properties were affected by several factors including the mPEG length, graft density and the sample concentration. These hydrogels displayed thermo-sensitive gel-sol transition under appropriate conditions due to the reversible mPEG and α -CD inclusion complexation. These hydrogels also showed pH-sensitive behavior due to the deprotonate of carboxylic acid side groups. The ICs formation of a channel-type crystalline structure induced gelation mechanism was verified by various techniques. In vitro cytotoxicity assays demonstrated that the supramolecular hydrogels are nontoxic and cytocompatible.

Immunosafety and chronic toxicity evaluation of monomethoxypoly(ethylene glycol)-b-poly(lactic acid) polymer micelles for paclitaxel delivery

Chang Li,Yan Shen,Chunmeng Sun,Nihad Cheraga,Jiasheng Tu

To investigate the physicochemical properties, immunosafety and chronic toxicity of monomethoxypoly(ethylene glycol)-b-poly(lactic acid) (mPEG-PLA), a copolymer used as a carrier for paclitaxel (PTX) delivery. The H-Nuclear Magnetic Resonance (H-NMR), dynamic light scattering and fluorescence probe technique were conducted to determine the physicochemical properties of mPEG-PLA copolymer. PTX-loaded polymeric micelles were characterized regarding their particle size, entrapment efficiency (EE), drug loading (DL), in vitro drug release and hemolysis rate. The complement activation in human serum and mast cells degranulation were performed by ELISA and RBL-2H3 cell line in vitro, respectively. The chronic toxicity study was carried out on beagle dogs. The optimized PTX-loaded mPEG-PLA (40/60) micelles showed a particle size of 37 nm and EE of 98.0% with a DL of 17.0% w/w. Transmission electron microscopy (TEM) analyses showed that mPEG-PLA (40/60) micelles have spherical shape with dense core. In vitro release study showed a sustained release for 24 h, and the hemolysis study revealed that mPEG-PLA (40/60) was a safe nanocarrier for intravenous administration. mPEG-PLA (40/60) showed a lower complement activation ability compared to mPEG-PLA (50/50) and Cremophor® EL (Cr EL). Furthermore, the chronic toxicity of PTX-loaded mPEG-PLA (40/60) micelles was significantly lower than those of mPEG-PLA (50/50) and Cr EL.

Synthesis and Characterization of a One-Dimensional Malleable Spin-Crossover Polymer Complex Modified by Methoxy Polyethylene Glycol

Di Wang,Ren Zhang,Jin Liu,Bibi Ji,Wenping Wang,Mengyuan Peng,Chen Huang,Lizhuoran Cheng,Yi Ding

A novel one-dimensional malleable spin-crossover (SCO) complex {[Fe(MPEG-trz)3](BF4)2} has been successfully synthesized by molecular self-assembly between 4-amino-1,2,4-triazoles (MPEG-trz) grafted with a long flexible chain methoxy polyethylene glycol (MPEG) and metallic complex Fe(BF4)2•6H2O. The detailed structure information was illustrated by using FT-IR and1H NMR measurements, while the physical behaviors of the malleable SCO complexes were systematically investigated by using magnetic susceptibility measurements using superconductivity quantum interference device (SQUID) and differential scanning calorimetry (DSC). This new metallopolymer exhibits a remarkable spin crossover transition behavior, between two spin quantum states (Fe2+ions): high spin (HS) state (quintet state) and low spin (LS) state (singlet state), at a specific critical temperature with a slender hysteresis loop of 1 K. DFT computations revealed the partial rules of HOMO-LUMO energy levels and spin density distributions of different four-position substituted [Fe(1,2,4-triazole)3]2+derivatives with different length of repeat units in polymer complexes. This can go a step further to depict the spin and magnetic transition behaviors of SCO polymer complexes. Furthermore, the coordination polymers possess an excellent processability due to an outstanding malleability, which can be easily shaped into a polymer film with spin magnetic switching properties.Keywords:spin crossover (SCO) complex;malleable;magnetic transition polymer;modification;MPEG films

Polymeric nanoparticles responsive to intracellular ROS for anticancer drug delivery

Long Xu,Mingying Zhao,Wenxia Gao,Yidi Yang,Jianfeng Zhang,Yuji Pu,Bin He

Thioketal and thioether are moieties used to fabricate reactive oxygen species (ROS)-responsive polymers for drug delivery. In this paper, three amphiphilic copolymers of mPEG-poly(ester-thioether), mPEG-poly(thioketal-ester) and mPEG-poly(thioketal-ester-thioether) were synthesized. The ROS-responsive behaviors of the three copolymers nanoparticles as drug carriers were investigated. The ROS-sensitivity was demonstrated by NMR, DLS, and SEM. mPEG-poly(ester-thioether) nanoparticles exhibited the fastest drug release rate, which possessed the best ROS sensitivity. The in vitro anticancer activity of the DOX-loaded nanoparticles was studied, the results revealed that the mPEG-poly(ester-thioether) nanoparticles showed the most efficient anticancer activity. Notably, all the three ROS-responsive copolymers nanoparticles showed enhanced cellular uptake and anticancer efficacy comparing to the control mPEG- b -PCL nanoparticles.

Self-assembly of polyion complex nanocarriers from ammonium glycyrrhizinate and monomethoxy poly(ethylene glycol)-b-poly(γ-amino-ε-caprolactone)

Yan Zhang,Jianjing Liu,Yutong Fu,Ke Tan,Zhaoyang Ye,Meidong Lang

A novel polyion complex (PIC) drug carrier was developed via electrostatic self-assembly in aqueous media based on our previous copolymer methoxy poly(ethylene glycol)-b-poly(γ-amino-ε-caprolactone) (mPEG-b-PACL) and anti-hepatotoxic drug ammonium glycyrrhizinate (AMG). The formation and the physicochemical properties of the polyion complex nanoparticles in aqueous solution were investigated by various methods. The results demonstrated that AMG was encapsulated successfully and the nanoparticles had a core–shell or tri-layer spherical structure based on the length of the PACL. The AMG/PACL PIC also displayed a high loading capacity and encapsulation efficiency of up to 41.8% and 91.7%, respectively. Furthermore, the nanoparticles enabled a continuous and sustained in vitro AMG release and the release half time was about 3 times that of the free AMG's. Results obtained by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, flow cytometry and fluorescence microscopy revealed that AMG loaded nanoparticles demonstrated greater prevention of liver cell apoptosis induced by lipopolysaccharide (LPS). These findings indicated that methoxy poly(ethylene glycol) (mPEG)-b-poly(γ-amino-ε-caprolactone) could be an efficient AMG carrier and could even be used as a delivery template for some other negatively charged water-soluble drugs or gene delivery systems.