Asian Journal of Pharmaceutical Sciences
·
2023
·
IF 10.2
Ka Hong Wong,Zhaopei Guo,Di Jiang,Xingzhi Zhou,Lizhu Lin,Denggao Zhao,Meiwan Chen
Nano drug delivery systems have made significant progress in delivering anticancer drugs camptothecin (CPT). However, many challenges for CPT delivery remain, including low drug loading efficiency, premature drug leakage, and poor cellular internalization. Herein, we report a novel dual-sensitive polypeptide-based micelle with remarkably high drug loading of CPT for cancer therapy. This self-assembled micelle possesses the following essential components for CPT: (1) pH-sensitive PEG (OHC-PEG-CHO) for prolonging blood circulation and allowing biocompatibility by shielding the cationic micelles, which can be detached under the tumor acidic microenvironment and facilitates the cellular uptake; (2) polypeptide polylysine-polyphenylalanine (PKF) synthesized via ring-opening polymerization for micelle formation and CPT analogue loading; (3) dimeric CPT (DCPT) with redox-sensitive linker for increasing CPT loading and ensuring drug release at tumor sites. Interestingly, the linear-like morphology of PEG-PKF/DCPT micelles was able to enhance their cellular internalization when compared with the spherical blank PKF micelles. Also, the anticancer efficacy of DCPT against lung cancer cells was significantly improved by the micelle formation. In conclusion, this work provides a promising strategy facilitating the safety and effective application of CPT in cancer therapy.
研究领域:
纳米医学
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癌症研究
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药剂学
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聚合物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2025
·
IF 4.9
Zhijie Liang,Jinzhuai Li,Hai Huang,Hongmian Jiang,Lifeng Luo,Shaorong Li,Huali Huang,Fangdi Hu
Pancreatic ductal adenocarcinoma (PDAC) poses significant therapeutic challenges due to its unique tumor microenvironment, which is characterized by collapsed blood vessels and elevated intratumoral pressure, severely hindering drug penetration and distribution. Consequently, we synthesized glucose-modified PEG-PLA (polyethylene-polylactice acid) nanoparticles as a drug delivery system for doxorubicin (DOX). We successfully enhanced the permeability and targeting capability of the nanoparticles in pancreatic cancer cells using glycosylation modification, significantly increasing drug accumulation within the tumor microenvironment. Our study demonstrated excellent cellular uptake of the nanoparticles in vitro and their improved penetration in 3D tumor spheroid models. Additionally, in vivo experiments revealed a notable increase in nanoparticle accumulation at the tumor site, along with favorable drug release characteristics. Hence, glucose-modified PEG-PLA nanoparticles hold substantial potential for clinical application in PDAC treatment, effectively enhancing the therapeutic efficacy of chemotherapeutic agents.
研究领域:
药剂学
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肿瘤学
✓ 已验证
产品关联
DOI
高影响因子
OPTICAL MATERIALS
·
2018
·
IF 2.32
Honghan Bu,Chen Xu,Guoyue Xu,Chuyang Liu,Shujuan Tan,Tengchao Guo,Shanshan Xiang
BCG/CaCl 2 /PEG-g-CDA composites with different mass ratios of BCG and CaCl 2 under constant PEG-g-CDA were synthesized via liquid-phase reaction method. The composites were analyzed and characterized using FT-IR, XRD , DSC and UV–vis. The results show that the color changes visibly from green to yellow by improving temperature from 50 °C to 62 °C, and turns back to green reversibly with temperature cooling back to room temperature. The infrared emissivity values increase rapidly at the temperature range of 50 °C–62 °C, and the maximum variation reaches 0.23. Furthermore, the mechanisms for thermochromic phenomenon and tunable infrared emissivity were also proposed. The reversible thermochromic phenomenon is attributed to the molecular structure transformation of BCG between ring-opened quinone structure and ring-closed lactone structure. The tunable emissivity at different temperatures is ascribed to the changes of resistivity under temperature fluctuations. Our results suggest that BCG/CaCl 2 /PEG-g-CDA composites are a potential candidate for smart adaptive camouflage in visible and infrared waveband.
研究领域:
材料科学
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光学
·
热力学
✓ 已验证
产品关联
DOI
高影响因子
DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY
·
2021
·
IF 3.232
Yang Gao,Ya Sun,Guangli Liao,Hailong Zhang,Qingzhi Long
Objective This study aims to investigate the potential of DSPE-PEG polymers (DSPE-PEG-OH and DSPE-PEG-SH) on improving absorption of poorly absorbable macromolecules via intrapulmonary administration and underlying mechanism.Methods In situ pulmonary absorption experiments were performed to investigate the absorption of model compounds after intrapulmonary administration to rats. The local membrane damage induced by these DSPE-PEG polymers were evaluated based on morphological observation of lung tissues and measurement of biological toxic markers in bronchoalveolar lavage fluid (BALF) postintrapulmonary delivery of DSPE-PEG polymers to rats. The underlying enhancement mechanism of these polymers was explored by investigating their effects on the pulmonary membrane fluidity and gene expression of tight junction associated proteins with fluorescence polarization and western blotting, respectively.Results Intrapulmonary delivery of these DSPE-PEG polymers significantly enhanced absorptions of poorly absorbed model drugs and did not induce serious damage to the pulmonary membranes of rats. Mechanistic studies demonstrated unaffected pulmonary membrane fluidity and up-regulated expression levels of tight junction-associated proteins by DSPE-PEG polymers, thus indicating that paracellular pathways might be included in the underlying mechanisms by which DSPE-PEG polymers exerted their enhancing actions on drug absorption.Conclusions These findings suggested that these DSPE-PEG polymers are potential for promoting absorptions of poorly absorbable macromolecules with no evidence of damage to the local pulmonary membranes of rats.Novelty statementIn this study, DSPE-PEG-OH and DSPE-PEG-SH polymers, two DSPE-PEG2000 conjugates with different terminal groups demonstrated significant promoting effects on the absorption of poorly absorbed macromolecular drugs after intrapulmonary delivery to rats, and did not induce serious damage to the pulmonary membranes of rats. These DSPE-PEG polymers could statistically downregulate expression levels of tight junction-associated proteins (ZO-1 and occludin), indicating the underlying mechanism by which these polymers exerted their absorption enhancing actions through pulmonary epithelial paracellular pathways. Thus, this study exhibited prospective potential of these DSPE-PEG polymers in developing into dosage forms with the aim to improve the poor bioavailability of some poorly absorbed macromolecular drugs.
研究领域:
药学
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药理学
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生物药剂学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2025
·
IF 9.6
Yu Hu Zhou,Zi Hao Zou,Jian Xiang Teng,Zhan Yu Wu,Si Wei Luo,Xu Ning,Chuan Ye,Long Yang,Wei Seong Toh
Avascular necrosis of the femoral head (ANFH) is a debilitating musculoskeletal disorder that is typically caused by impaired blood supply to the hip joint. In treating irregular bone defects that resulted from ANFH, injectable hydrogels are particularly attractive as they can be administered in a minimally invasive manner and conform to the variable shape of a bone defect. However, they often lack the biochemical and mechanical properties for effective bone repair. To address these issues, an injectable composite hydrogel, SA/β-TCP@PMP, composed of sodium alginate (SA) and β-tricalcium phosphate (β-TCP) crosslinked with glucono-delta-lactone (GDL), and enforced with varying concentrations of poly(3-hydroxybutyrate- co -4-hydroxybutyrate)/magnesium oxide and polyethylene glycol (P34HB/MgO+PEG; PMP) coaxial electrospun microfibers are formulated. By varying the concentrations (0%, 1%, 2%, 4%) of PMP microfibers, the physical properties of the composite hydrogel, including its injectability, surface morphology, swelling, degradation, and mechanical properties, as well as magnesium ions (Mg 2+ ) release can be finely tuned. Among all, SA/β-TCP@2%PMP composite hydrogel demonstrates superior angiogenic and osteogenic properties, and promotes robust new bone formation in a rabbit model of steroid-induced ANFH. Overall, this novel composite hydrogel offers significant application potential for minimally invasive treatment of irregular bone lesions in ANFH.
研究领域:
生物医学工程
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骨科
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材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2023
·
IF 8
Yongai Xiong,Tingting Chen,Lei Chen,Rongshan Cai
Introduction Radiotherapy and chemotherapy are the fundamental causes of myelosuppression in cancer patients, which usually induce a serious hematopoietic system toxicity, causing the hemocytes and immunity decline of patients. Ziyuglycoside I (ZgI), an active ingredient isolated from traditional Chinese medicine Sanguisorba officinalis L, has been demonstrated to increase the leucocytes and protect hematopoietic stem cells, which is related to its promotion of autophagy in hematopoietic stem cells.Methods In the present study, we formulated the SH-PEG-NH2-coated gold nanoparticles loading ZgI (ZgI-AuNPs) with a enhanced autophagy promotion in hematopoietic stem cells. ZgI-AuNPs were prepared by HAuCl4-sodium citrate reduction method, and the synthesis of ZgI-AuNPs was validated by XRD, FT-IR, DSC, and TEM findings. Furthermore, the drug loading rate and the release of ZgI were evaluated, and the ZgI-AuNPs’ effects on autophagy and immunofluorescence staining for LC3B were tested. Finally, the effect of ZgI-AuNPs on the autophagy and hematopoietic ability of HSCs in vivo was also carried out.Results The prepared ZgI-AuNPs have an irregular cubic crystal structure by TEM observation, and the average particle size was 340 ± 16.5 nm determined by DLS. The XRD, FT-IR and DSC detection showed that the ZgI had been well loaded in AuNPs, and the AuNPs can load the ZgI at a content of 160.63 ± 1.35 μg·mg−1. Meanwhile, the AuNPs can reduce the drug release rate of ZgI. Importantly, the ZgI-AuNPs enhanced autophagy of HSCs both in vitro and in vivo. At the same time, the gold nanoparticles enhance the hematopoietic effect of ZgI on mice HSCs.Conclusion Our research suggests that SH-PEG-NH2-coated gold nanoparticles loading ZgI has potential application in myelosuppression therapy.
研究领域:
纳米技术
·
药理学
·
血液学
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肿瘤学
✓ 已验证
DOI
PubMed
高影响因子
Polymer Chemistry
·
2018
·Vol. 9
·期 25
·3488-3498
·
IF 4.927
Yue Ding,Chang Du,Jiwen Qian,Linzhu Zhou,Yue Su,Rong Zhang,Chang-Ming Dong
To overcome the tumor and cellular barriers in cancer chemotherapy, the construction of biodegradable polymeric nanomedicine with pathological stimuli-responsivity is still challenging. In this work, a new class of polypeptide copolymer nanoparticles with a sheddable PEG corona and a dynamic disulfide bond cross-linked core was fabricated in aqueous solution, which can respond to tumor pH and intracellular reductive milieu. The polypeptide block copolymer (i.e., PEG-D-PC) composed of hydrophilic poly(ethylene glycol) (PEG) and thiol-pendant poly(L-cysteine) (PC) was synthesized via the primary amine terminated PEG dimethylmaleic anhydride derivative initiated ring-opening polymerization of α-amino acid N-carboxyanhydride and a sequential photocleavage reaction. The size and zeta potential change of the core-cross-linked (CCL) nanoparticles was monitored by on-line dynamic light scattering at pH 6.5, 10 mM DTT, and pH 6.5 + 10 mM DTT, respectively. In a similar manner, the anticancer drug camptothecin (CPT)-loaded CCL nanoparticles exhibited dual-stimuli-triggered drug release profiles. The CPT-loaded CCL79 nanoparticles facilitated the cellular internalization and CPT release inside the HeLa cells at pH 6.5, as confirmed by flow cytometry and fluorescence microscopy. The half maximal inhibitory concentration of CPT-loaded CCL79 nanoparticles at pH 6.5 was greatly lowered 31.8 fold to 0.61 μg CPT equiv. per mL compared to that at pH 7.4 + 0.1 mM BSO inhibitor, presenting dual stimuli-triggered cytotoxicity.
研究领域:
生物材料学
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药物递送系统
·
肿瘤学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF MEMBRANE SCIENCE
·
2023
·
IF 9.5
Bin Xiang,Jingling Gong,Yuqing Sun,Wenhao Yan,Ruirui Jin,Jian Li
Unstable interlayer spacing of lamellar membranes would be rapidly compressed and narrowed under normal high flowrates and concentration polarization effect contributes to reduced permeation and fouling resistance. Herein, a large permeability PEG/MXene@MOF membrane with stable interlayer spacing and superior antifouling property was created via facile interface self-assembly strategy. Metal-organic framework ( MOF , UiO-66-NH 2 ) nanoparticles as supports constructed an intercalation-induced structure with hierarchical Ti 3 C 2 T x (MXene) nanosheets , which effectively regulated the interlayer spacing and improved permeability. Hydrophilic polyethylene glycol (PEG) further enhanced the stability of intercalation structure via hydrogen bonding , so that the PEG/MXene@MOF membrane demonstrated excellent swelling resistance with an average layer spacing expansion of only 0.05 nm even after immersion in water for 8 days. Moreover, MOF particles increased the lamellar roughness and interlayer water retention capacity, resulting in the PEG/MXene@MOF membrane with remarkable separation selectivity and powerful fouling resistance (UWOCA >156°, UWOSA <5.5°). Regarding the purification of oil-in-water emulsions stabilized by surfactants , the PEG/MXene@MOF membrane exhibited extremely stable high permeability (1246 ± 12 L m −2 h −1 bar −1 ) and excellent efficiency (>99.7 %), even during continuous separation of high-viscosity crude oil emulsions for 60 min. In addition, the PEG/MXene@MOF membrane also exhibited superior chemical durability and mechanical robustness in strong-corrosiveness and high-salty environments (72 h), ultrasonic treatments (120 min), bending experiments (100 times) and abrasion tests (20 times). Therefore, this work provided a promising strategy to construct highly permeable membrane with stable interlayer spacing and efficient fouling resistance for practical oily wastewater purification.
研究领域:
膜技术
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水处理
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纳米材料
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环境工程
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材料科学
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表面化学
✓ 已验证
DOI
高影响因子
International Journal of Nanomedicine
·
2019
·
IF 4.471
Fei Tong,Xiangyuan Tang,Daojun Liu
Background Hepatic ischemia/reperfusion-induced pancreatic islet injury (HI/RIPII) was an important pathophysiological phenomenon in clinics. In the present study, we observed the effects of phycocyanin on HI/RIPII. However, the half-life of phycocyanin was extremely short and limited its use in vivo.Materials and methods In order to overcome this shortcoming, poly(ethylene glycol)-b-(poly(l-glutamic acid)-g-polyethylenimine) (PEG-b-(PG-g-PEI)) was synthesized and estimated as a nanocarrier for lengthening delivery of phycocyanin through the abdominal subcutaneous injection in rats. Phycocyanin (isoelectric point=4.3) was encapsulated with PEG-b-(PG-g-PEI) via electrostatic interactions at pH 7.4.Results In vitro phycocyanin was fast and efficiently encapsulated and showing efficient loading and sustained release. In vivo the anti-HI/RIPII function of phycocyanin/PEG-b-(PG-g-PEI) complex was surveyed in rats using free phycocyanin as the controls, and the results showed that phycocyanin/PEG-b-(PG-g-PEI) complex reduced HI/RIPII property and enlarged islet functionality.Conclusion These results suggested that PEG-b-(PG-g-PEI) might be treated as a potential phycocyanin nanocarrier.
研究领域:
药理学
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纳米技术
·
医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Polymer Chemistry
·
2018
·Vol. 9
·期 40
·5032-5042
·
IF 4.927
Haoyu Liu,Guolin Lu,Chun Feng,Xiaoyu Huang
A new monomer, 2-(difluoromethoxy)ethyl acrylate (DFMOEA), was first synthesized from commercially available 2-hydroxyethyl acrylate via a one-step difluoromethylation reaction. A series of well-defined poly(2-(difluoromethoxy)ethyl acrylate) (PDFMOEA) homopolymers were prepared via atom transfer radical polymerization (ATRP) of DFMOEA initiated by 2-bromopropionate. The Mn of the obtained polymer increased linearly with the monomer conversion, and the dispersities were low throughout the polymerization (Mw/Mn < 1.20) though some bimolecular recombination and side reactions occurred during the polymerization. The glass transition temperature (Tg) of the homopolymers obtained by using differential scanning calorimeter (DSC) is about −44 °C, 9 °C higher than that of poly(2-methoxyethyl acrylate) (PMOEA) homopolymer, which indicated that the introduction of difluoromethoxyl is beneficial for increasing the Tg. ATRP of DFMOEA initiated by a PEG-based macroinitiator provided poly(ethylene glycol)-b-poly(2-(difluoromethoxy)ethyl acrylate) (PEG-b-PDFMOEA) amphiphilic diblock copolymers with low dispersities (Mw/Mn < 1.26). The critical micelle concentrations (cmc) of PEG-b-PDFMOEA amphiphilic diblock copolymers in aqueous solution were determined by fluorescence probe technique and the cmc values decrease gradually with the increase of the length of hydrophobic PDFMOEA segment. It was found that PEG-b-PDFMOEA amphiphilic block copolymers could self-assemble into spherical micelles with a diameter of around ca. 45 nm in aqueous media which were visualized by transmission electron microscopy (TEM).
研究领域:
材料科学
·
高分子化学
✓ 已验证
DOI
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2022
·
IF 5.062
Yusheng Sun,Peng Zhang,Feng Zhang,Mengyang Pu,Wentao Zhong,Yu Zhang,Yingchao Shen,Baoqi Zuo
Silk fibroin nanofiber hydrogels mimicking the extracellular matrix structure have gained increased attention in the field of tissue engineering. In this study, an amorphous silk fibroin nanofiber solution was prepared using a new dissolving technique. The keys to the dissolving method include the preparation of nanofibrous silk film by dissolving silk in a CaCl 2 -Formic Acid (Ca-FA) solution with subsequent dissolution in a CaCl 2 -Ethanol-H 2 O ternary solution at room temperature. The resulting solution was primarily composed of native silk nano/microfibers, which primarily form amorphous structures. The amorphous silk fibroin nanofiber solution was further processed into an injectable hydrogel through a simple physical blend with polyethylene glycol (PEG). The nanofiber structure and PEG accelerated silk gelation, and the fastest gelation time was 150 s at concentrations of 5% silk and 85% PEG. The morphology, secondary structure, and rheological properties of injectable silk fibroin nanofiber hydrogels were subsequently characterized. Silk gelation was accompanied by a structural transition from random coil to β-sheet, and the resulting injectable hydrogel had an irregular lamellar structure. The antibiotic vancomycin (VANCO) was loaded in the injectable hydrogel, and the release of VANCO from the injectable hydrogel was assessed at pH values of 4.5 and 7.4. The VANCO-loaded injectable silk fibroin nanofiber hydrogel exhibited superior antibacterial properties against bacteria. A cytotoxicity test preliminarily demonstrated that the VANCO-loaded injectable silk fibroin nanofiber hydrogel had good biocompatibility for applications in tissue engineering.
研究领域:
组织工程
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生物材料
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药物递送系统
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
NEW JOURNAL OF CHEMISTRY
·
2023
·Vol. 47
·期 26
·12431-12444
·
IF 3.3
Hailiang Chen,Chenyu Liu,Simiao Yu,Hengjun Zhou,Farishta Shafiq,Weihong Qiao
Polyethylene glycol (PEG), which can impart long cycling performance to drug carriers, has been commonly used for drug carrier modification. However, PEG modification impedes cellular uptake of drug carriers and intracellular release of drugs, a problem known as the “PEG dilemma” that limits its application. In this study, we designed and synthesized mPEG-NCH-DOB molecules with acid-sensitive hydrazone bonding for the responsive removal of PEG. Drug-loaded lipid PHDGX for doxorubicin (DOX) delivery was obtained by compounding mPEG-NCH-DOB with lipid DOPG, which possess the capability for long cycling, and acid-sensitive PEG-removal to accelerate drug release and enhance cellular uptake. mPEG-NCH-DOB could reach 50% fracture rate after 24 h at pH 5.0. The cytotoxicity assay and flow cytometry (FCM) results showed that PHDGX could enter A549/ADR cells more easily than free DOX at low DOX concentrations and has stronger anti-cancer ability. Through a confocal laser-scanning microscopy (CLSM) study, PHDGX was found to enter the nucleus of A549/ADR cells more easily than free DOX at the same time point, which indicated that PHDGX could overcome the DOX resistance of A549/ADR at low DOX concentrations. The 3D tumor microsphere (MC) growth inhibition assay showed that PHDGX not only has the best MC inhibition ability but also has better MC penetration ability than free DOX. Therefore, this drug-loaded liposome has good stability under conventional conditions and responsive PEG removal in the tumor acid environment, offering a potential strategy for utilizing PEG in drug carrier modification and overcoming tumor resistance to free drugs.
研究领域:
药学
·
纳米技术
·
癌症治疗
·
药物递送系统
✓ 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）