查找使用阿拉丁产品的科研文献

Stable, Bioresponsive, and Macrophage-Evading Polyurethane Micelles Containing an Anionic Tripeptide Chain Extender

Danxuan Fang,Menghan Pi,Zhicheng Pan,Nijia Song,Xueling He,Jiehua Li,Feng Luo,Hong Tan,Zhen Li

Polymeric nanocarriers have been extensively used in medicinal applications for drug delivery. However, intravenous nanocarriers circulating in the blood will be rapidly cleared from the mononuclear macrophage system. The surface physicochemical characterizations of nanocarriers are the primary factors to determine their fate in vivo, such as evading the reticuloendothelial system, exhibiting long blood circulation times, and accumulating in the targeted site. In this work, we develop a series of polyurethane micelles containing segments of an anionic tripeptide, hydrophilic mPEG, and disulfide bonds. It is found that the long hydrophilic mPEG can shield the micellar surface and have a synergistic effect with the negatively charged tripeptide to minimize macrophage phagocytosis. Meanwhile, the disulfide bond can rapidly respond to the intracellular reduction environment, leading to the acceleration of drug release and improvement of the therapeutic effect. Our results verify that these anionic polyurethane micelles hold great potential in the development of the stealth immune system and controllable intracellular drug transporters.

Exploring structure influence of mPEG-PLGA nanocarriers on their interaction with physiopathological barriers in the lung and anti-lung cancer effect

Qiaoyu Liu,Juanjuan Chai,Xinrui Zhang,Jingwen Xue,Lu Qin,Jian Guan,Xin Zhang,Bingjie Ma,Shirui Mao

Inhalable nanomedicines hold great promise for lung cancer therapy, yet how carrier structure dictates their pulmonary fate remains insufficiently understood. From a fundamental research perspective, this study aims to investigate how structurally distinct nanocarriers interact with physiopathological barriers in the lungs, with the goal of providing a theoretical foundation for inhalation therapy. By keeping the composition and material properties of the carriers comparable, different structured paclitaxel-loaded mPEG-PLGA nanocarriers, including nanoparticles, polymersomes, and micelles, were prepared by selecting different hydrophobic chain mPEG-PLGA diblock copolymers. It was found that nanoparticles with solid structure showed the slowest drug release rate, and the strongest cellular uptake but are difficult to overcome the barriers in the lung mucus with limited tumor permeability. In contrast, polymersomes with a less rigid structure have a better capacity to overcome the mucus and tumor barrier and therefore have the best lung retention but the weakest cellular uptake. The micelles with the smallest particle size have the strongest tumor permeability and the most prominent lymphatic distribution but the fastest drug release rate thus the most prominent extrapulmonary distribution. Remarkably, despite these divergent behaviors, their overall antitumor efficacy converged, revealing a compensatory balance among structural advantages and limitations. By bridging mechanistic insights with therapeutic outcomes, this study establishes a structure–function framework for pulmonary delivery. These findings advance fundamental understanding of how nanocarrier structure shapes drug fate and efficacy and provide generalizable principles to guide the rational design and clinical translation of inhalable nanomedicines for lung cancer and other pulmonary diseases.

Dual thermoresponsive mPEG-b-poly(O-benzyl-l-threonine acid) hydrogel based on β-sheet nano-structural disassembly and PEG dehydration

Hongyu Zhu,Yu Liu,Dongxu Gu,Zikun Rao,Yang Li,Jianyuan Hao

It is a challenging work to design novel responsive materials by controlling the secondary structure of polypeptide , especially β-sheet. We designed and synthesized a novel dual responsive diblock copolymer of methyl poly (ethylene glycol)- b -poly (O-benzyl- l -threonine) (mPEG- b -PBnLT). The copolymer solutions exhibited unusual and reversible gel-to-sol-to-gel transition behavior with temperature, and the transition temperature window could be easily adjusted by changing copolymer concentration or PBnLT block length . It was confirmed that low temperature gel-to-sol transition was due to the disassembly of the preliminary β-sheet layered nano-assemblies that induced the transformation of self-organized morphology from nanosized fibrils to spherical aggregates, while the high temperature sol-to-gel transition was ascribed to the dehydration of PEG segments. The disassembly of β-sheet structures was caused by the change in the polarity of the pendant benzyl ether bond of PBnLT block in water with temperature. This stimuli-responsiveness of secondary self-assembled nanostructures and the corresponding change in macroscopic phase transition inspires a brand-new strategy for structural design and functional control of polypeptide materials.

Enhancement of oral bioavailability and anti-colitis effect of luteolin-loaded polymer micelles with RA (rosmarinic acid)-SS-mPEG as carrier

Zhaomin Lu,Juan Liu,Liangjian Zhao,Chenli Wang,Feng Shi,Zhengqi Li,Xuesong Liu,Zhiwei Miao

Objective Polymer micelles were prepared (L-RSPMs) with luteolin and synthetic RA-SS-mPEG polymeric material before evaluation of their anti-inflammatory effect on 2, 4, 6-trinitro-benzene-sulfonic acid (TNBS)-induced ulcerative colitis (UC) model in rats.Methods The synthetic RA-SS-mPEG was characterized with NMR spectroscopy, before preparation of luteolin-coated RA-SS-mPEG polymer micelles. The in vitro characterization and evaluation of the formulation were accomplished, couple with its pharmacokinetic parameters. The levels of PEG2, MDA, CRP and GSH, as well as concentrations of TNF-α, IL1-β, IL-6 and IL-10 in serum and colon tissue were detected via ELISA kit. The degree of colon injury and inflammation was evaluated via histopathologic examination.Results L-RSPMs displayed small average droplet size (133.40 ± 4.52 nm), uniformly dispersed (PDI: 0.163 ± 0.011), good stability, slow release and enhanced solubility. We observed 353.28% increase in the relative bioavailability of L-RSPMs compared to free luteolin, while the half-life of the micelle was extended by 6.16h. Compared to model (M) group, luteolin (low and high doses) and L-RSPMs (low and high doses) significantly reduced levels of MDA, PEG2, CRP, TNF-α, IL-6 and IL-1β in colon tissue and serum of colitic rats but dose dependently increased IL-10 and SOD levels (p < 0.01). Histopathologic examination of colon showed that luteolin (low and high doses) and L-RSPMs (low and high doses) improved colonic inflammation in colitic rats to varying degrees compared to M group.Conclusion L-RSPMs could improve TNBS-induced colon inflammation by enhancing bioavailability, promoting antioxidant effects and regulating cytokine release, which may become a potential agent for UC treatment in clinical settings.

Ionically crosslinked alginate-based nanohydrogels for tumor-specific intracellular triggered release: Effect of chemical modification

Tingting Zhou,Jiagen Li,Peng Liu

A facile one-pot approach has been developed to prepare novel pH-responsive ionic nanohydrogels with high drug-loading capacity and desirable size for tumor-specific intracellular triggered release of anticancer drug DOX , in which the ionic crosslinking of alginate (AL) or its derivatives (oxidized alginate (OAL) or PEGylated OAL (mPEG-OAL)) and the DOX-loading ocurred simultaneously. It was found that the modification was benificial to the formation of the DOX-loaded ionic nanohydrogels with smaller diameter and narrower size distribution, even with similar DOX loading capacity. Especially for the mPEG-OAL, the resultant mPEG-OAL/DOX ionic nanohydrogels showed a hydrodynamic diameter of 135 nm with very narrow size distribution. All the three DOX-loaded ionic nanohydrogels (AL/DOX, OAL/DOX, and mPEG-OAL/DOX) showed the pH-responsive characteristic, and the last one exhibited the best capacity for controlled release, in a sustained release mode.

A tumor targeted nano micelle carrying astragaloside IV for combination treatment of bladder cancer

Kong Chenfan,Sun Jianrong,Hu Xinzi,Li Guangzhi,Wu Song

Immune checkpoint inhibitors (ICIs) are effective agents for tumor immunotherapy. However, their clinical effectiveness is unsatisfactory due to off-target effects and a suppressive immune microenvironment. This study developed a nanodrug delivery system for bladder cancer (BCa) using PCL-MPEG and PCL-PEG-CHO to synthesize internal hydrophobic and external hydrophilic micelles (PP) that encapsulated water-insoluble astragaloside IV (PPA). The aldehyde group on the surface of PPA reacted with the amino group of aPD-L1, allowing the decoration of this antibody on the surface of the micelles. The resultingPPA@aPD-L1effectively piggybacked astragaloside IV and aPD-L1 antibody. These findings suggest that PPA@aPD-L1 is relatively stable in circulation and efficiently binds to BCa cells with the aid of aPD-L1. Additionally, this strategy prolongs the drug’s retention time in tumors. Compared to PBS, PP, and PPA with PPA + aPD-L1 groups, PPA@aPD-L1significantly prolonged the survival of mice with BCa and reduced tumor volume. Mechanistic studies showed that PPA inhibited the NF-κB and STAT3 signaling pathways in tumor cells. Additionally, PPA@aPD-L1increased IFN-γ and decreased IL-10 expression in bladder tumors, affecting the number and type of intratumorally infiltrating T cells. Our study presents a simple and effective drug delivery system that combines herbal monomers with ICIs. It has demonstrated a potent ability to suppress tumor growth and holds potential for future applications.

Micelles-Encapsulated with Azithromycin and Ibuprofen for Synergistic Antibacterial at Different pH

Feng Runliang,Chen Shiyu,Zhao Yingshun,Wang Mingzhu,Li Yuli,Jia Yunjing,Song Zhimei

Purpose To improve azithromycin’s antibacterial activity at different pH through combination therapy. Method Azithromycin- and ibuprofen-loaded micelles were fabricated by the self-assembly of MPEG-PVL copolymer, respectively. Results The drug-loaded micelles had controlled drug release property with water-solubility improvement. Notably, at pH 7.4 or 6.0, the in vitro antibacterial experiments demonstrated that there was no synergistic effect for the two native drugs against S. aureus , but a significant synergy was observed when the two preparations were used in combination. In vitro PI fluorescence staining experiment demonstrated that the introduction of ibuprofen-loaded micelles obviously increased cellular uptake under low concentration of azithromycin-loaded micelles. Through SEM and spectral evaluation experiments, it was found that ibuprofen-loaded micelles could increase the cell permeability by interacting with proteins and phospholipids in the cell membrane, which was conducive to promoting azithromycin-loaded micelles to enter the cells and play a drug effect. Conclusion The azithromycin- and ibuprofen-loaded micelles with synergistically enhanced antibacterial activity are potential candidates for effective bacterial combination therapy. Graphical Abstract

Design, Synthesis, and Characterization of Schiff Base Bond-Linked pH-Responsive Doxorubicin Prodrug Based on Functionalized mPEG-PCL for Targeted Cancer Therapy

Yinglei Zhai,Xing Zhou,Zhiqiang Zhang,Lei Zhang,Dianyu Wang,Xinhui Wang,Wei Sun

The side effects of doxorubicin (DOX) extremely limit its application in the treatment of malignant tumors. Nano-sized polymeric drugs based on the acidic microenvironment of tissular- or intra- tumor have attracted ample attention because of their potential in reducing side effects. In this research, an amphiphilic diblock copolymer based on poly (ethylene glycol) (PEG) and functionalized polycaprolactone (PCL) was synthesized and utilized as the drug carrier. DOX was chemically conjugated with the polymer via acid-cleavable imine bonds to obtain a novel pH-sensitive DOX prodrug (mPEG-PCL-Imi-DOX). mPEG-PCL-Imi-DOX (24.2 wt % DOX content) formed micelles with an average diameter of 125 nm through a simple solvent evaporation method. The in vitro release profile demonstrated that DOX release of the prodrug micelles was pH-responsive and able to be accelerated with the decrease of pH. In vitro cytotoxicity assay tests revealed that the pH-sensitive DOX prodrug micelles exhibited relatively lower toxicity and similar antitumor efficacy towards MCF-7 cells compared with free DOX. Hence, the DOX prodrug micelles with imine bonds can offer a carrier with great potential for chemo-therapeutics.Keywords:doxorubicin;pH-sensitive;prodrug;micelles;imine

Preparation of intravenous injection nanoformulation via co-assemble between cholesterylated gemcitabine and cholesterylated mPEG: enhanced cellular uptake and intracellular drug controlled release

Yanyun Xu,Xin Zhong,Xiongwen Zhang,Wei Lv,Jiahui Yu,Yi Xiao,Shiyuan Liu,Jin Huang

Baicalein Loaded Crown Ether-mPEG-PLGA Micelle Drug Delivery System for Increased Breast Cancer Treatment: Preparation, Characterization, In-Vitro and In-Vivo Evaluations

Ji Shun-Li,Zhang Chun-Yan,Yin Xiao-Qin,Wang Jing,Wang Jia-Peng,Xu Xin

Due to low aqueous solubility and poor bioavailability of the flavone baicalein (BIC), a nano-micelle of delivery system was developed. Preparation of BIC-loaded crown ether-mPEG-PLGA micelle (BCPP-M) was performed via thin-film hydration method. Characterization of micellar excipients was accomplished with 1H NMR, while evaluation of the optimal BCPP-M formulation was appropriately carried out through zeta potential (ZP), size of particles (PS), efficiency of encapsulation (EE) and capacity of drug loading (DL). We evaluated BIC release In-Vitro and profile of In-Vivo pharmacokinetics. Evaluation of the anti-breast cancer property of BCPP-M using MCP-7 cells cytotoxicity and mice model was performed. Particles of BCPP-M were homogenously and spherically shaped with smaller average PS, coupled with higher EE and DL, good stability and polydispersity index (PDI). The accumulative release of BCPP-M was obviously higher than free-BIC. Significantly, oral biological availability of BCPP-M was improved comparable to free BIC. Besides, half maximum inhibitory concentration (IC50) of BCPP-M in MCP-7 cells was lower than free-BIC. Animal experiments also showed targeting, long circulation and antitumor potential of BCPP-M. Successful incorporation of BIC into long-acting and targeting micellar system could have enhanced solubility in aqueous media, oral In-Vivo availability and antitumor property of BIC.

AgFeS2 nanoparticles as a novel photothermal platform for effective artery stenosis therapy

Xuan Peng,Junchao Liu,Chen Ming,Bo Li,Zhen Zhao,Kaichuang Ye,Min Zeng,Rujia Zou,Xinwu Lu,Junqing Hu

Ternary I–III–VI2 semiconductors usually have narrow band gaps and large absorption coefficients arising from the unique characteristics of their outer-d valence electrons, which are intimately connected with the photothermal conversion properties. AgFeS2 is known as one such material that has the potential to absorb near-infrared light. In this work, we utilized density functional theory (DFT) calculations to evaluate the electronic structure and optical absorption properties of AgFeS2. Strong absorptions were predicted over a wide Vis-NIR region due to the localized 3d electron of Fe atoms, which agree quite well with the UV-Vis-NIR spectra measured by experiment. The as-prepared AgFeS2 nanoparticles were then modified with mPEG-DSPE, an efficient photothermal agent for artery stenosis therapy. Its photothermal conversion effect has been systematically studied, indicating the potential for causing the hyperthermia of macrophages, an essential part of the artery inflammation response. More importantly, both in vitro cell experiments and in vivo mouse-model studies show that the induction of hyperthermia in artery stenosis by using AgFeS2 nanoparticles is safe and effective when injected at a very low concentration. This study provides a novel photothermal platform derived from the inheritability of bandgap structure and also promotes the process of artery inflammation and stenosis therapy.

20(S)-Ginsenoside Rg3-loaded electrospun membranes to prevent postoperative peritoneal adhesion

Qiu Renna,Li Jian,Sun Denghua,Li Hongjun,Qian Feng,Wang Lizhe

Postoperative peritoneal adhesions are one of the most common surgical complications. In this study, we developed a 20(S)-ginsenoside Rg3-loaded methoxy poly (ethylene glycol)-block-poly(L-lactide-co-glycolide) (mPEG- b -PLGA) electrospun membrane (PEM/Rg3) that could not only serve as a physical barrier, but also as a drug delivery system that releases 20(S)-ginsenoside Rg3 constantly to prevent postoperative peritoneal adhesions. The characteristics of PEM/Rg3, including scanning electron microscopy, water contact angle, and mechanical analyses, were assessed. Degradation and drug release assays of PEM/Rg3 were performed. The anti-adhesion efficacy of PEM/Rg3 was evaluated in an abdomen-cecum mouse model. The adhesion scores, adhesion areas, hematoxylin and eosin (H&E) staining, immunofluorescence, and western blotting were assessed. The 20(S)-ginsenoside Rg3 loaded mPEG- b -PLGA electrospun fibers were successfully fabricated. The fibers were smooth, with no obvious drug crystals. PEM/Rg3 membranes were biodegradable and could be degraded gradually to release 20(S)-Ginsenoside Rg3 constantly from the membranes. The animal study showed that PEM/Rg3 exhibited an excellent adhesion prevention ability when compared with the control group, the PEM group, and polylactic acid (PLA) commercial membrane (Surgiwrap™) group. Immunofluorescence and western blotting studies showed that PEM/Rg3 inhibited the expressions of interleukin 1 (IL-1), interleukin 6 (IL-6), and reactive oxygen species modulator-1 (ROMO1). The 20(S)-ginsenoside Rg3-loaded mPEG- b -PLGA electrospun membranes exhibited satisfactory anti-adhesion efficacy by inhibiting inflammatory responses and oxidative stress. This composite represents a promising strategy to prevent postoperative peritoneal adhesions.