ACS Applied Nano Materials
·
2024
·
IF 5.3
Qiuxiang Li,Guowei Zhao,Fengling Wu,Xilan Tang,Zhenggen Liao,Xinli Liang,Wei Dong
Imperatorin (IMP) has demonstrated potential in reversing drug resistance in various tumor cells; however, its limited clinical application and development are attributed to its poor water solubility and low bioavailability. The current work is intended to enhance the oral bioavailability of IMP and its efficacy in overcoming tamoxifen (TAM) resistance in breast cancer cells. We employed mPEG–PLLA and Cremophor RH60 (RH60) to prepare imperatorin nanomicelles (IMP-RH60/mPEG–PLLA). The freeze-dried powder of IMP-RH60/mPEG–PLLA demonstrated a porous structure, and upon reconstitution, the resulting solution exhibited clarity and transparency. The particle size was measured to be 25.48 ± 0.92 nm, with a zeta potential of −5.50 ± 1.06 mV. The encapsulation efficiency was determined to be 85.78 ± 0.84%, while the drug loading was found to be 2.66 ± 0.03%. In comparison to the active pharmaceutical ingredients (APIs) of IMP, IMP-RH60/mPEG–PLLA exhibited a significant increase in in vitro release, improved bioavailability in rats, and enhanced uptake by MCF-7/TAM cells. The coadministration of IMP-RH60/mPEG–PLLA and TAM effectively inhibited the proliferation, colony formation, migration, and invasion of MCF-7/TAM cells. This outcome could potentially be attributed to the downregulation of GST-π and MDR1 drug resistance genes, consequently augmenting the susceptibility of MCF-7/TAM cells to TAM. An experimental model of BALB/c nude xenograft, consisting of human breast cancer cells resistant to tamoxifen (TAM), was established in order to assess the potential in vivo reversal of TAM resistance through the use of IMP-RH60/mPEG–PLLA. The growth of xenografts was inhibited by IMP-RH60/mPEG–PLLA, and it induced apoptosis in tumor tissues through the downregulation of Ki-67, GST-π, and MDR1 gene expression. The findings indicated that the utilization of IMP-RH60/mPEG–PLLA micelles resulted in an enhancement of IMP’s bioavailability and its efficacy in overcoming TAM resistance.
研究领域:
药学
·
肿瘤学
·
纳米技术
·
药理学
✓ 已验证
产品关联
DOI
高影响因子
REACTIVE & FUNCTIONAL POLYMERS
·
2019
·
IF 3.074
Chuang Zhou,Ziming Yang,Li Zhang,Enming Dong,Zuyu He,Xianwu Liu,Chao Wang,Yan Yang,Jing Jiao,Yunhao Liu,Yu Chen,Puwang Li
In this work, carboxymethyl chitosan-graft-eleostearic acid (CMCS-g-EA) was synthesized via the amide reaction between the amino groups of carboxymethyl chitosan and the carboxyl group of eleostearic acid, and then mPEG-NH 2 was grafted to CMCS-g-EA to prepare amphiphilic polymers (mPEG-CMCS-g-EA). The chemical structures of the above conjugates were characterized by FT-IR and 1 H NMR. Both CMCS-g-EA and mPEG-CMCS-g-EA based nano-vesicles were prepared by ultrasonic self-assembly method and they exhibited a low critical aggregation concentration (CAC) of 14.97 μg/mL, 16.82 μg/mL, respectively. The spinosad-loaded mPEG-CMCS-g-EA nano-vesicles (SSD@mPEG-CMCS-g-EA NVs) were spherical in shape with an average diameter of 502.8 nm and the zeta potential of −25.60 mV. The encapsulation efficiency (EE) and drug loading content (LC) of SSD@mPEG-CMCS-g-EA nano-vesicles were 42.00%, 23.07%, respectively. In vitro release revealed that the SSD@mPEG-CMCS-g-EA nano-vesicles exhibited a sustained and pH-responsive drug release property, and could significantly enhance the photostability of spinosad . Furthermore, the toxicological tests demonstrated that the SSD@mPEG-CMCS-g-EA nano-vesicles could efficiently inhibit the growth and development of Helicoverpa armigera . These results indicated that the SSD@mPEG-CMCS-g-EA nano-vesicles were highly potential for the treatment of Helicoverpa armigera .
研究领域:
农药科学
·
生物材料学
·
昆虫学
✓ 已验证
DOI
高影响因子
Nanoscale Research Letters
·
2021
·Vol. 16
·期 1
·1-16
·
IF 4.703
Zhou Lin,Huang Zhi,Yang Shanyi,Wei Jiarui,Xu Yan,Hu Lin,Guo Xinrong,Yuan Limin,Yuan Zexuan,Yang Xiaoping,Tao Xiaojun,Zhang Qiufang
Hydrophilic polyethylene glycol monomethyl ether (mPEG) was grafted onto Icariin (ICA) by succinic anhydride to form a polyethylene glycol-Icariin (mPEG-ICA) polymer. The structure of the polymer was characterized by Fourier transform infrared spectroscopy (FT-IR) and nuclear magnetic resonance spectroscopy (NMR). mPEG-ICA nanoparticles loaded with ICA were prepared by physical embedding of ICA by dialysis. The particle size was determined to be (220 ± 13.7) nm, and the ζ potential was (2.30 ± 1.33) mV by dynamic light scattering (DLS). Under a transmission electron microscope (TEM), the nanoparticles were spherical, and the morphology was regular. In the medium with pH 7.4, the drug release rate of mPEG-ICA nanoparticles reached (52.80 ± 1.70)% within 72 h. At pH 6.8, the cumulative drug release of nanoparticles reached (75.66 ± 0.17)% within 48 h. Treatment of the nanoparticles with LPS-treated H9c2 cells maintained cell viability, reduced LDH release and exerted antiapoptotic effects. Moreover, ICA-loaded mPEG-ICA nanoparticles significantly decreased the mRNA expression of the myocardial inflammatory cytokines TNF-α, IL-1β and IL-6M. In conclusion, ICA-loaded mPEG-ICA nanoparticles protected against LPS-induced H9c2 cell injury.
研究领域:
药学
·
纳米技术
·
细胞生物学
·
炎症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF BIOMATERIALS APPLICATIONS
·
2017
·
IF 2.31
Hailiang Li,Chaoping Fu,Xiangwan Miao,Quanming Li,Juan Zhang,Huikang Yang,Tao Liu,Xi Chen,Minqiang Xie
The gene and drug co-delivery system has become one of the primary strategies to overcome cancers. Here, we designed a multifunctional magnetic co-delivery system for nasopharyngeal carcinoma-targeted therapy and MR imaging. Aldehyde sodium alginate (ASA) was used to decorate the oxide iron and load cisplain through coordinate bond to form a core complex. The polymer shell poly(l-lysine)-methoxy-polyethylene glycol-folate was used to coat the core complex through electric interaction to give this nano-medicine a target ability. And this polymer could also give the nano-medicine abilities to adhere and protect DNA, and enhance its solubleness in water. After being transfected with this nano-medicine, the plasmids which contain cancer suppressor gene TFPI2 could enter and express in HNE-1 cells. It caused a higher death and apoptosis rate, inhibited nasopharyngeal carcinoma cells’ migration and cloning by the synergic effect together with cisplain. Besides, clear images of this nano-medicine could be got under T2 MR imaging. This magnetic co-delivery system demonstrates a potential as a powerful multifunctional vector for drug delivery and gene vector applications in nasopharyngeal carcinoma.
研究领域:
癌症治疗
·
分子生物学
·
医学影像
·
纳米医学
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2022
·
IF 5.988
Xi Chen,Di Wang,Xuejun Guo,Xiaoming Li,Wenjing Ye,Yang Qi,Wen Gu
The present study was aim to prepare curcumin-loaded methoxypolyethylene-glycols-poly (lactic-co-glycolic acid) nanoparticles (Cur-mPEG-PLGA-NPs) and investigate curcumin's effect on reversing corticosteroid resistance induced by cigarette smoke extract (CSE) in rat tracheal epithelial (RTE) cells. The Cur-mPEG-PLGA-NPs were spherical, regular in shape with smooth surfaces, and well distributed and Cur-mPEG-PLGA-NP suspensions had good water solubility and presented prolonged release. Furthermore, we found that Cur-mPEG-PLGA-NPs were internalized more than curcumin into the cells and significantly alleviated apoptosis in RTE cells. In addition, 10% CSE reduced the maximal inhibition percentage and increased the half-inhibitory concentration of budesonide (BUD) on IL-8 secretion, and curcumin restored the efficacy of BUD inhibition. BUD in combination with Cur-mPEG-PLGA-NPs showed higher inhibitory rates for LPS- and CSE-induced IL-8 secretion than that in combination with curcumin. Moverover, the relative expression levels of HDAC2 was reduced after CSE exposure and curcumin could improve HDAC2 expression and reverse CSE-induced corticosteroid resistance. Curcumin in high concentration and Cur-mPEG-PLGA-NPs restored HDAC2 levels in RTE cells and thus Cur-mPEG-PCL-NPs have higher biological activity than curcumin.
研究领域:
药理学
·
纳米技术
·
呼吸医学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
AAPS PHARMSCITECH
·
2022
·Vol. 23
·期 7
·1-13
·
IF 4.026
Cao Xia,He Qing,Adu-Frimpong Michael,Shen Xinyi,Rong Wanjing,Li Xiaoxiao,Zhang Jian,Xia Xiaoli,Shi Feng,Ji Hao,Toreniyazov Elmurat,Wang Qilong,Yu Jiangnan,Xu Ximing
Pinocembrin (PCB) is 5,7-dihydroxyl flavanone and has multiple pharmacological activities, namely, anti-inflammation, anti-osteoporotic, and so on. However, low water solubility and bioavailability have hindered its application. Herein, we aimed to increase its bioavailability through preparation of F127/MPEG-PDLLA polymer micelles (PCB-M). We characterized the micelles through appropriate attributes such as analysis of particle size (PS), polydispersity (PDI), transmission electron microscopic (TEM) image, stability test, and evaluation of in vitro release of drug. After physical characterization, the respective PS, PDI, and entrapment efficiency (EE) of PCB-M were estimated to be 27.63 ± 0.17 nm, 0.055 ± 0.02, and 90.53 ± 0.01%. Fluorescence probe method was employed to measure critical micelle concentration (CMC) of PCB-M, we observed CMC was low, thereby suggesting that PCB-M had good stability. In vitro release analysis indicated that the rate of cumulative PCB release from PCB-M was greater than 90% in each medium compared with free PCB, which was less than 40%, thus pointing to a significantly improved solubility of PCB. In vivo pharmacokinetic results showed that oral biological availability of PCB-M increased 5.3 folds comparable to free PCB. The effects of PCB on osteoblasts and ALP activities were investigated; subsequently, zebrafish osteoporotic model was established with prednisolone to study the anti-osteoporotic effects of PCB and PCB-M. The results showed that PCB improved osteoporosis with PCB-M being more effective than free PCB. Finally, PCB-M can be used as a promising method to improve the solubility of PCB, while the bioavailability and anti-osteoporotic effect of PCB could be improved, thus laying a foundation for clinical use in the future. Graphical Abstract
研究领域:
药学
·
药理学
·
材料科学
·
生物医学工程
·
骨骼研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF MEDICINAL CHEMISTRY
·
2025
·
IF 6.8
Yunhai Wei,Wenjing Hu,Huancen Guo,Jinyu Zhang,Jingrui Cao,Chu Shen,Zhongxin Wu,Lei Yin,Yuhai Gao
Immune checkpoint inhibitors (ICIs) show effectiveness in gastric cancer (GC) treatment, yet enhancing their efficacy remains challenging. We encapsulated the anticancer compound Heterophyllin B (HB) in mPEG–PLGA-NH2 nanoparticles (NPs), modified with αPDL1, forming mPEG–PLGA-NH2@HB-αPDL1 NPs. These NPs displayed low toxicity to GES-1 cells and good blood compatibility. They effectively inhibited GC cell malignant phenotypes and downregulated PD-L1 expression via the PI3K/AKT pathway. In GC allograft mice, the HB and αPDL1 combination therapy outperformed monotherapy, with the NPs showing better efficacy than free drugs. Additionally, the NPs improved the tumor immune microenvironment. H&E staining confirmed no significant toxicity to major mouse organs. Thus, mPEG–PLGA-NH2@HB-αPDL1 offers a promising strategy for optimizing ICI therapy in GC treatment.
研究领域:
纳米医学
·
肿瘤学
·
免疫治疗
·
药物递送系统
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2020
·
IF 7.182
Renliang Lyu,Ting Xia,Cheng Liang,Cheng Zhang,Zeqin Li,Lichun Wang,Yi Wang,Ming Wu,Xiaogang Luo,Jiayu Ma,Cunwen Wang,Caili Xu
Three kinds of novel environmentally benign and high-efficiency crude oil demulsifiers were prepared using methoxy polyethylene glycol (MPEG) to modify alkylated carboxymethyl chitosan (ACMC). Structures of the demulsifiers were confirmed using FT-IR and 1 H NMR, and the relationship between surface tension and concentration was tested. Demulsification performance was investigated using the bottle test method with oil-in-water (O/W) emulsions that were prepared in lab conditions. The demulsification efficiency was as high as 79.1 %–84.9 %, and the possible mechanism of the demulsification process is discussed. Results show that MPEG-grafted ACMC (MPEG-ACMC) has a promising application as a demulsifier for dealing with emulsified O/W crude oil.
研究领域:
化学工程
·
环境科学
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF APPLIED POLYMER SCIENCE
·
2017
·Vol. 135
·期 7
·45867
·
IF 1.86
Guangtan Fan,Renliang Lyu,Xiao Gao,Cheng Liang,Cunwen Wang
Four novel environmentally friendly and highly branched crude oil demulsifiers were prepared by using different molecular weight ( M n = 350, 750, 1000, 1900 g/mol) of methoxy poly(ethylene glycol) to modify quaternized N,O-carboxymethyl chitosan. Fourier transform infrared and 1 H-nuclear magnetic resonance were employed to confirm the structure of the demulsifiers. The surface tension of demulsifies was determined and hydrophile–lipophile balance value was calculated at the critical micelle concentration. The demulsification performance was evaluated by the bottle test method against water-in-oil emulsions simulated in the laboratory and it was found that the dehydration rate of four demulsifiers can come to 74.2%–80.4%, which have better demulsification performance than the commercial demulsifier JL-1. Demulsification mechanism was discussed, and it was encouraging to find that the tiny water droplets in the emulsion coalesced to form the water phase and separated with the water from the polarization microscope. Results show that methoxy poly(ethylene glycol) grafted quaternized carboxymethyl chitosan has a promising application as a demulsifiers for dealing with W/O crude oil emulsions. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135 , 45867.
研究领域:
化学工程
·
材料科学
·
环境科学
✓ 已验证
产品关联
DOI
高影响因子
ChemistrySelect
·
2023
·Vol. 8
·期 29
·e202301647
·
IF 2.1
Fen Zheng,Jianghuan Shi,Shanming Zhang,Kaige Liu,Long Xu
Graphical A novel containing cinnamaldehyde pH-sensitive biodegradable linear copolymer carrier mPEG- b -poly(Schiff base-acetal) was designed and synthesized, which could co-delivery of cinnamaldehyde and gemcitabine to same tumor cells and pH-responsive release cinnamaldehyde and gemcitabine for double drug synergistic antitumor therapy. Due to significant pH difference among the healthy tissue, tumor tissue as well as intracellular endo/lysosome, constructing pH-responsive biodegradable nanodrug delivery systems has received more and more attention. Herein, double-end alkenylated acetal monomer (based on cinnamaldehyde (CA)) and double-end sulfhydrylation Schiff base monomer were designed and synthesized, and three pH-responsive biodegradable block copolymer mPEG- b -poly(Schiff base-acetal) (P1), mPEG- b -poly(acetal) (P2), and mPEG- b -poly(Schiff base) (P3) were obtained by Michael addition reaction. All these polymers could be self-assembled with gemcitabine (GEM) to form GEM-loaded micelles. Proton nuclear magnetic resonance ( 1 H NMR) and dynamic light scattering (DLS) experiments proved that these polymer micelles have good pH responsiveness. The size and morphology of both blank and GEM-loaded micelles were characterized by DLS and scanning electron microscope (SEM). The GEM/P1, GEM/P2, and GEM/P3 micelles exhibited pH-sensitive drug release properties and the GEM/P1 micelles has the relatively fastest drug release rate. Containing multiple acetal and Schiff base moieties GEM/P1 micelles showed fastest cellular internalized rate and best in vitro antitumor activity among all GEM-loaded micelles.
研究领域:
药学
·
材料科学
·
肿瘤学
✓ 已验证
产品关联
DOI
高影响因子
RSC Advances
·
2015
·Vol. 5
·期 27
·20890-20899
·
IF 3.84
Minghui Xu,Junmin Qian,Aili Suo,Weijun Xu,Rongrong Liu,Hongjie Wang
Combination of chemotherapy and small interfering RNA (siRNA)-based therapy has emerged as a promising approach for cancer treatment with the synergistic effect. In this study, a novel terpolymer methoxy poly(ethylene glycol)-block-poly(N,N-dimethylaminopropyl methacrylamide)-block-poly(acrylhydrazine) (mPEG-b-PDMAPMA-b-PAH) with a disulfide linkage between mPEG and PDMAPMA blocks was developed for the intracellular targeted co-delivery of adriamycin and P-gp siRNA. The terpolymer was synthesized by sequential reversible addition–fragmentation chain transfer (RAFT) polymerization of N,N-dimethylaminopropyl methacrylamide and N-tert-butoxycarbonyl-N′-acryl hydrazine (Boc-acrylhydrazine) in the presence of a PEGylated macro-RAFT agent, followed by Boc-deprotection. The terpolymer could chemically conjugate adriamycin via an acid-cleavable hydrazone bond and simultaneously condense the negatively charged siRNA through electrostatic interactions at an N/P ratio of 2. The resultant adriamycin-conjugated nanoparticles/siRNA complexes (ADR-NPs/siRNA complexes) showed a spherical morphology and had an average diameter of 186 nm. The release profiles of the two payloads from the ADR-NPs/siRNA complexes exhibited a pH/reduction dual-dependent sustained release behavior. The ADR-NPs/siRNA complexes could simultaneously deliver adriamycin and siRNA efficiently into MCF-7/ADR cells and significantly inhibit their growth in a synergistic fashion. All the results indicated that the terpolymer mPEG-b-PDMAPMA-b-PAH could serve as a potential vehicle for the combination of chemotherapy and gene therapy.
研究领域:
药学
·
纳米技术
·
癌症研究
·
聚合物化学
·
药物递送系统
✓ 已验证
产品关联
DOI
高影响因子
DRUG DELIVERY
·
2022
·
IF 6.819
Yanhai Xi,Weiheng Wang,Liang Ma,Ning Xu,Changgui Shi,Guohua Xu,Hailong He,Wenming Pan
Astragaloside (AS) has an anti-osteoporotic effect, but its poor water solubility and low bioavailability limit its application. In this study, a novel nano-carrier with bone targeting was prepared by modifying mPEG-PLGA with alendronate (AL) before incorporation into astragaloside nano-micelles (AS-AL-mPEG-PLGA) to enhance the oral bioavailability, bone targeting and anti-osteoporosis effect of AS. The release behavior of AS-AL-mPEG-PLGA in vitro was investigated via dialysis. The pharmacokinetics of AS-AL-mPEG-PLGA was studied in Sprague-Dawley (SD) rats. The cytotoxicity of AS-AL-mPEG-PLGA in vitro (via MTT method), coupled with bone targeting ability in vitro and in vivo were evaluated. The therapeutic effects of free AS and AS-AL-mPEG-PLGA (ELISA, micro-CT, H&E staining) were compared in osteoporotic rats. AS-AL-mPEG-PLGA with smaller particle size (45.3 ± 3.8 nm) and high absolute zeta potential (−23.02 ± 0.51 mV) were successfully prepared, wherein it demonstrated higher entrapment efficiency (96.16 ± 0.18%), a significant sustained-release effect for 96 h and acceptable safety within 10–200 μg/mL. AS-AL-mPEG-PLGA could enhance the hydroxyapatite affinity and bone tissue concentration of AS. The relative bioavailability of AS-AL-mPEG-PLGA was 233.90% compared with free AS. In addition, the effect of AS in reducing serum levels of bone metabolism-related indicators, restoring the bone microarchitecture and improving bone injury could be enhanced by AS-AL-mPEG-PLGA. AS-AL-mPEG-PLGA with small particle size, good stability, remarkable sustained-release effect, safety and bone targeting was successfully constructed in this experiment to potentially improve the oral bioavailability and anti-osteoporosis effect of AS. Thus, AS-AL-mPEG-PLGA may be a promising strategy to prevent and treat osteoporosis.
研究领域:
药剂学
·
药理学
·
纳米技术
·
骨生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）