COLLOIDS AND SURFACES B-BIOINTERFACES
·
2024
·
IF 5.4
Na Liang,Yingxue Xu,Wei Zhao,Zhenrong Liu,Gang Li,Shaoping Sun
In this study, an amphiphilic polymer FA-CS-DBA-CHO with aggregation-induced emission (AIE) feature was prepared by introducing 4-(diphenylamino)benzaldehyde derivative (DBA-CHO), imine bond and folic acid (FA) to the molecular structure of chitosan (CS). The amphiphilicity drove the polymer to self-assemble into micelles, and paclitaxel (PTX) could be solubilized in the hydrophobic core. Due to the excellent AIE effect, FA-CS-DBA-CHO exhibited strong cellular imaging capability. The pH-sensitive imine bond in the polymer allowed for accurate drug release in acidic environment. Both in vitro and in vivo studies demonstrated that the PTX-loaded FA-CS-DBA-CHO micelles could significantly inhibit the growth of tumor cells but without any notable toxicity. This micellar system was excellent carrier for bioimaging and chemotherapeutic drug delivery.
研究领域:
材料科学
·
生物学
·
医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOPARTICLE RESEARCH
·
2024
·Vol. 27
·期 1
·1-14
·
IF 2.1
Li Tingyuan,Li Jiaying,Wang Qilong,Gong Mingjie,Wang Xiaowen,Jiang Xia,Hua Qinyang,Ji Hao,Toreniyazov Elmurat,Yu Jiangnan,Cao Xia,Adu-Frimpong Michael,Xu Ximing
Isorhamnetin (ISO) is a kind of flavonoid widely found in sea buckthorn, ginkgo biloba, and other plants. It has many pharmacological activities, but poor solubility in aqueous media has limited its clinical application. In order to increase the bioavailability of ISO, we employed a thin film dispersion method to prepare ISO-loaded Soluplus-TPGS mixed polymer micelle (ISO-STM) and subsequently conducted appropriate characterizations. The micelles prepared in this work were spherical nanoparticles with uniform distribution with respective particle size (PS) and dispersion coefficient (PDI) of 81.62 ± 1.23 nm and 0.115 ± 0.020. Meanwhile, the encapsulation rate (EE) was 91.37% ± 0.82%, whereas the drug loading (DL) was 5.91% ± 0.06%. Compared to free ISO, the dissolution rate of mixed micelles (MM) significantly increased in three media. After oral administration, the oral bioavailability of MM was nearly 3 times higher than free ISO’s. In addition, the results of the zebrafish experiment showed that the anti-aging of zebrafish in the administration group was significantly better than that in the model control group. In summary, ISO-STM is a promising method with the potential to improve the solubility, and bioavailability and enhance the clinical application value of ISO.
研究领域:
药剂学
·
药理学
✓ 已验证
产品关联
DOI
高影响因子
Polymers
·
2024
·Vol. 16
·期 24
·3485
·
IF 4.7
Meizhen Yin,Xinying Zhang,Tongguang Zhang,Zhiqiang Bao,Zhihui He
The present study aimed to explore an ideal delivery system for triptolide (TPL) by utilizing the thin-film hydration method to prepare drug-loaded, folate-modified mixed pluronic micelles (FA–F-127/F-68–TPL). Scanning electron microscopy and atomic force microscopy showed that the drug-loaded micelles had a spherical shape with a small particle size, with an average of 30.7 nm. Cell viability experiments showed that FA–F-127/F-68–TPL significantly reduced HepG2 cell viability, exhibiting strong cytotoxicity. Its cytotoxicity was markedly enhanced compared with bare TPL. Nile red (Nr) was used as a model drug to prepare FA–F-127/F-68–Nr to further validate its tumor-targeting and cellular uptake capability. After coincubation with HepG2 cells, a multifunctional microplate reader showed that intracellular fluorescence intensity significantly increased, indicating that FA–F-127/F-68–Nr could more effectively enter the cells. A nude mouse model of subcutaneous hepatocellular carcinoma was constructed. Following tail vein injection of FA–F-127/F-68–Nr, the fluorescence imaging system showed that FA–F127/F-68–Nr could significantly target tumor tissue, and even if entering the small-sized tumor was challenging, it could be excreted through urine. Nude mice with subcutaneous hepatocellular carcinoma were treated with tail vein injections of FA–F-127/F-68–TPL (45 µg/kg) every other day for 21 days. The results showed that the growth of the transplanted tumors was significantly slowed, with no significant difference compared with bare TPL. In summary, the FA–F-127/F-68–TPL exhibits the advantages of low cost, excellent biological properties, active/passive targeting capabilities, notable cytotoxicity against liver cancer cells, and significant inhibition of transplanted hepatocellular carcinoma growth. Significantly, the FA–F-127/F-68–TPL, despite challenges in targeting tumors with an insignificant EPR effect, can be efficiently excreted via the kidneys, thereby preventing the release of the drug during prolonged circulation and potential damage to normal tissues. Therefore, FA–F-127/F-68–TPL represents a promising antitumor drug delivery system.
研究领域:
药剂学
·
肿瘤学
·
生物材料
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2024
·
IF 9.4
Linhan Ni,Min Li,Jia Xie,Ke Chen,Yue Yang,Yuqun Zhou,Zhigao Zhu,Junwen Qi,Jiansheng Li
The desalination performance of thin film nanocomposite (TFN) membranes is significantly influenced by the nature of nanofillers and the structure of the polyamide (PA) layer. Herein, a micelles regulated interfacial polymerization (MRIP) strategy is reported for the preparation of TFN membranes with enhanced nanofiltration (NF) performance. Specially, stable and ultrafine micelles, synthesized from the poly(ethylene oxide)- b -poly(4-vinyl pyridine)- b -polystyrene (PEO-PVP-PS) triblock copolymers, were utilized as regulators in the aqueous phase during the interfacial polymerization (IP) process. TFN membranes were fabricated with varying concentrations of micelles to improve their properties and performances. The structure of the PA layer was further regulated by modulating the content of trimesoyl chloride (TMC), which significantly enhances the performance of the TFN membrane with micelles. Attributable to the homogeneously dispersed micelles and the modified PA layer, the optimized membrane denoted as TFN-2–0.3 exhibits an improved separation performance of 20.7 L m -2 h −1 bar −1 and 99.3 % Na 2 SO 4 rejection, demonstrating nearly twice the permeance and 2.7 % higher rejection than that of the original control membrane, respectively. The mechanism of this MRIP strategy was investigated through the diffusion experiments of piperazine (PIP) and interfacial tension tests. The incorporated micelles effectively lower the interfacial tension, promote the diffusion of PIP and accelerate the IP reaction, resulting in a denser and thinner PA layer. Collectively, these findings demonstrate that TFN membranes with micelles exhibit increased roughness, enhanced hydrophilicity, superior rejection to divalent salts, and better acid-base resistance, highlighting their potential applications in the design of TFN membranes.
研究领域:
材料科学
·
环境工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
·
2021
·
IF 4.539
Maosong Xuan,Ju Liang,Junbo Li,Wenlan Wu
Curcumin (CUR) is a kind of natural polyphenol with low aqueous solubility, poor bioavailability and favorable antitumor activity. In order to enhance anti-tumor activity and efficient delivery of CUR, an amphiphilic lipopeptide (C 18 H 5 R 7 RGDS, LP) containing H 5 R 7 RGDS heads and stearic acid (C 18 ) tails was prepared by solid-phase peptide synthesis. Spherical LP micelles of ∼50 nm were self-assembled in PBS (pH 7.0) with good dispersion and significantly improved the aqueous solubility of CUR by 5400 times more than that of free CUR. The sequence of H 5 in LP endowed the CUR-loaded LP micelles with good pH-responsive drug release behavior. In the case of pH 5.0, the electrostatic repulsion interaction among the ionized H 5 fraction destroyed the structure of micelles, leading to significantly accelerated CUR release behavior. Hemolysis assay and proliferation inhibition test of normal cells confirmed apparently the excellent biocompatibility of LP. CUR-loaded LP micelles showed much higher cell growth inhibition on HepG2 cells and lower cytotoxicity on L02 cells than free CUR. With integrin-targeting sequence (RGD) and cell penetrating peptide (R 8 ), LP micelles can more specifically and efficiently deliver CUR into integrin-overexpressed HepG2 cells than C 18 KR 8 (LP-R 1 ) and C 18 KRGDS (LP-R 2 ) micelles. Combined with the enhanced drug solubility, distinctive pH-sensitive property and good tumor targeting, such LP micelles may have the clinical potential for tumor-targeting delivery.
研究领域:
药学
·
生物技术
·
纳米技术
·
肿瘤学
✓ 已验证
产品关联
DOI
高影响因子
REACTIVE & FUNCTIONAL POLYMERS
·
2021
·
IF 3.975
Yong Gao,Amin Deng,Xionghui Wu,Changsheng Sun,Chenze Qi
Injectable multi-responsive hydrogels are very important and exhibit many potential applications in biologically relevant fields. In this work, the preparation of injectable multi-responsive hydrogels at near-physiological conditions and their applications as durg carriers were demonstrated. Diol-capped poly( N, N -dimethylacrylamide)- b -poly( N -isopropylacrylamide) ((OH) 2 -PDMA- b -PNIPAM) diblock copolymers containing a disulfide linkage on the backbone and N, N -dimethylacrylamide- stat -(2-acrylamidophenylboronic acid) (DMA- stat -2APBA) copolymers were separatedly synthesized. Hydrogels were then prepared by a solution-based mixing of DMA- stat -2APBA with (OH) 2 -PDMA- b -PNIPAM diblock copolymers in PBS (pH 7.4) solution at a given temperature, i.e. 37 °C. Above the lower critical solution temperature (LCST) of diblock copolymers at around 32 °C, (OH) 2 -PDMA- b -PNIPAM copolymers self-assembled into core-shell structured macromolecular micelles with numerous diol groups on hydrophilic cornoas. Subsequent complexiation of diols with lateral PBA groups of DMA- stat -2APBA copolymers led to the formation of hydrogels. Due to the integration of a library of responsive units including boronate ester and disulfide DCBs together with thermal responsive PNIPAM blocks within the same system, the as-prepared hydrogels indicated multiple stimuli-responsiveness to pH, temperature, glucose and redox reaction as well as the mechanical field. Such multi-responsive hydrogels could be applied as potential drug carriers. The encapsulation and the stimuli-responsive release of a model drug of Rh B were demonstrated.
研究领域:
生物材料学
·
药剂学
✓ 已验证
产品关联
DOI
高影响因子
FOOD HYDROCOLLOIDS
·
2020
·
IF 7.053
Qing Liu,Fang Li,Na Ji,Lei Dai,Liu Xiong,Qingjie Sun
Natural amphiphilic polymer micelles are of great interest as a carrier of hydrophobic functional ingredients due to their relatively easy synthesis, biocompatibility, and extensive sources. This study modified debranched starch (DBS) with acetic anhydride to introduce the hydrophobic acetyl group, and micelles were then obtained through the self-assembly of acetylated debranched starch (ADBS). The degree of substitution (DS) and the structural and thermal properties of ADBS were systematically investigated; the maximum DS value was 0.17. Proton nuclear magnetic resonance spectra of ADBS confirmed the presence of acetyl methyl protons, and Fourier transform infrared spectra exhibited a new absorption band of carbonyl C = O vibration at 1730 cm −1 due to the introduction of acetyl. The developed micelles were mostly spherical, and the particle size was about 50–100 nm. The critical micelle concentration was 0.45 mg/mL. Curcumin was incorporated into the micelles successfully, and the curcumin-loaded micelles exhibited sustained release properties in simulated gastric and intestinal fluids.
研究领域:
食品科学与工程
·
生物材料学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION
·
2015
·
IF 1.648
Ju Liang,Wenlan Wu,Danyu Lai,Junbo Li,Cailin Fang
A lipopeptide (LP)-containing KKGRGDS as the hydrophilic heads and lauric acid (C12) as the hydrophobic tails has been designed and prepared by standard solid-phase peptide synthesis technique. LP can self-assemble into spherical micelles with the size of ~30 nm in PBS (phosphate buffer saline) (pH 7.4). Curcumin-loaded LP micelles were prepared in order to increase the water solubility, sustain the releasing rate, and improve the tumor targeted delivery of curcumin. Water solubility, cytotoxicity, in vitro release behavior, and intracellular uptake of curcumin-loaded LP micelles were investigated. The results showed that LP micelles can increase the water solubility of curcumin 1.1 × 103 times and sustain the release of curcumin in a low rate. Curcumin-loaded LP micelles showed much higher cell inhibition than free curcumin on human cervix carcinoma (HeLa) and HepG2 cells. When incubating these curcumin-loaded micelles with HeLa and COS7 cells, due to the over-expression of integrins on cancer cells, the micelles can efficiently use the tumor-targeting function of RGD (functionalized peptide sequences: Arg-Gly-Asp) sequence to deliver the drug into HeLa cells, and better efficiency of the self-assembled LP micelles for curcumin delivery than crude curcumin was also confirmed by LCSM (laser confocal scanning microscope) assays. Combined with the enhanced solubility and higher cell inhibition, LP micelles reported in this study may be promising in clinical application for targeted curcumin delivery.
研究领域:
药剂学
·
肿瘤学
·
生物材料
✓ 已验证
产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2017
·Vol. 7
·期 73
·45978-45986
·
IF 3.108
Na Wen,Chunmei Gao,Shaoyu Lü,Xiubin Xu,Xiao Bai,Can Wu,Piao Ning,Shaofei Zhang,Mingzhu Liu
The high pKa (8.26 to 8.6) of PBA has restricted its glucose-responsiveness in physiological conditions, and the high cytotoxicity of polymers is also a limiting problem in their potential application for insulin delivery. Novel amphiphilic glucose-sensitive dialdehyde starch polymers containing 3-aminophenylboronic acid (APBA) as a glucose-responsive group and mPEGylated dialdehyde starch (mPEG-DAS) with hydrophobic 7-hydroxycoumarin-4-acetic acid (Cou) were synthesized. This dialdehyde starch derivative can self-assemble into mPEG-DAS–APBA–Cou micelles with “shell–core” structures in phosphate-buffered saline solution (PBS). In addition, the drug-loaded micelles can release insulin rapidly in response to hyperglycemia in a physiological environment. The results demonstrated that the mPEG-DAS–APBA–Cou micelles showed notable glucose responsive behavior near the physiological range. The insulin release from the nanocarriers is sensitive to different concentrations of glucose, releasing insulin rapidly under the conditions of 3 mg mL−1 glucose while demonstrating comparatively inert release at 1 mg mL−1 glucose (pH 7.4). MTT assays and hemolysis studies both confirmed that the mPEG-DAS–APBA–Cou micelles have low cytotoxic activity to A549 cells and low blood toxicity. These results suggest that the glucose-sensitive dialdehyde starch micelles (mPEG-DAS–APBA–Cou) have potential applications as a glucose-responsive material for insulin delivery.
研究领域:
药学
·
纳米技术
·
生物材料
·
药物递送系统
✓ 已验证
产品关联
DOI
高影响因子
ChemPlusChem
·
2016
·Vol. 81
·期 11
·1237-1244
·
IF 2.836
Pei Zhang,Wenxiu He,Huiyuan Zhang,Chunzhi Huang,Dujuan Zhao,Yuxia Luan
Graphical Critical micelles concentrate on cancer : Mixed micelles made of a disulfide-linked drug–polymer conjugate and a polymer–folate conjugate were tested as a targeted, redox-sensitive delivery system (PEG–PBLG-SS-DTX/PEG–FA) for the anticancer drug docetaxel (DTX). The results showed improved anticancer efficiency of DTX delivered by these micelles to folate-receptor-expressing MCF-7 cancer cells. The objective of this study was to build mixed micelles based on two functional co-polymers, including the redox-sensitive polymer–drug conjugate methoxy poly(ethylene glycol)–poly(γ-benzyl l -glutamate)-disulfide-docetaxel (PEG–PBLG-SS-DTX) and the actively targeting methoxy poly(ethylene glycol)–folic acid (PEG–FA), for enhanced target specificity and improved anticancer efficiency of docetaxel (DTX). The spherical PEG–PBLG-SS-DTX/PEG–FA mixed micelles prepared by the dialysis method revealed a narrowly distributed size at 129.7±2.1 nm with low polydispersity of 0.10±0.02. Furthermore, the critical micelle concentration of the mixed micelles was 5.08 μg mL −1 , indicating excellent self-assembly ability in water and stability against dilution in blood circulation. The in vitro release study revealed that the conjugated DTX was rapidly released in response to dl -dithiothreitol (DTT), a reducing agent. Only 12.3 % of DTX was released from the mixed micelles after 120 h in the absence of DTT. However, the accumulative release of DTX dramatically accelerated and reached more than 40 % in 120 h after addition of DTT. The in vitro cytotoxicity, cellular uptake and cell apoptosis experiments on the mixed micelles were performed using MTT assay, fluorescence inverted microscopy and flow cytometric analysis, and 4′,6-diamidino-2-phenylindole (DAPI) staining, respectively, on folate receptor (FR)-negative A549 and FR-positive MCF-7 cells. The mixed micelles could be taken up efficiently by MCF-7 cells by FR-mediated endocytosis compared with PEG–PBLG-SS-DTX micelles. Furthermore, remarkable cytotoxicity and cell apoptosis were identified for the mixed micelles against MCF-7 cells, which was consistent with the results of the cellular uptake study. On the basis of these results, the redox-sensitive PEG–PBLG-SS-DTX/PEG–FA mixed micelles using FA as a targeting ligand revealed prominent antitumor efficiency and might be a latent drug carrier for cancer chemotherapy.
研究领域:
药学
·
癌症研究
·
纳米技术
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Scientific Reports
·
2016
·Vol. 6
·期 1
·1-10
·
IF 5.228
Zhang Lan,Tan LiWei,Chen LiJuan,Chen XiaoXin,Long ChaoFeng,Peng JinRong,Qian ZhiYong
Self-assembled polymeric micelles have been widely applied in drug delivery systems. In this study, we found that pH value of micellar system solution was the decisive factor of physical stability. Furthermore, the weak basic solution could maintain the solution clarification for a relative long time. To investigate the stability of polymeric micelles in different pH solutions, the micellar particle size and the docetaxel content remaining in solution were detected at predetermined time points. The crystallographic assay of freeze-drying powder was characterized by an X-ray diffractometer. In vitro release results indicated that the PBS had little influence on the sustained-release effect of docetaxel-loaded polymeric micelles (DPM). Besides, the safety of micellar formulation was determined by an MTT assay on HEK293 cells, and the anti-tumor activity was tested on MCF-7 cells. The results demonstrated that DPM adjusted with PBS (DPM (PBS)) was of low toxicity and maintained the effectiveness of docetaxel. In vivo antitumor results indicated that DPM (PBS) had better antitumor efficacy than common docetaxel injection (DTX). Thus it was concluded that regulation of micellar solution PH by PBS is a safe and effective method to improve the physical stability of DPM. It might promote the application of micellar formulation in clinical applications.
研究领域:
药剂学
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF MATERIALS CHEMISTRY
·
2012
·Vol. 22
·期 33
·16865-16871
·
IF 5.968
Gong-Yan Liu,Chao-Jian Chen,Dan-Dan Li,Shan-Shan Wang,Jian Ji
Near-infrared light-sensitive polymeric micelles were prepared for the enhanced intracellular delivery of doxorubicin (DOX). The micelles were prepared from dextran-graft-(2-diazo-1,2-naphthoquinone) (Dex-DNQ) amphiphilic copolymers which were synthesized by modification of hydrophilic dextran with hydrophobic DNQ molecules. The hydrophobic DNQ molecule is an attractive photo-trigger group because its UV/NIR-induced Wolff rearrangement can result in a drastic change into a hydrophilic 3-indenecarboxylic acid (3-IC) molecule with pKa of 4.5. Thus, under UV or NIR irradiation, Dex-DNQ micelles will rapidly release encapsulated drugs due to the micelle dissociation. DOX was chosen as an anticancer drug to be encapsulated into the Dex-DNQ micelle with the loading efficiency and content of 60% and 24%, respectively. In vitro cell viability studies, the micelles exhibited higher intracellular DOX release under NIR irradiation at 808 nm, which resulted in significant growth inhibition of HepG2 cancer cells. Fluorescence microscopy and flow cytometry further proved the enhanced intracellular drug release behaviour of DOX-loaded Dex-DNQ micelles under NIR irradiation. We are convinced that this smart drug nanocarrier is potentially useful for cancer chemotherapy.
研究领域:
药剂学
·
肿瘤学
·
生物材料学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）