Applied Materials Today
·
2022
·
IF 8.663
Ruirui Zhang,Liping Zhong,Xiuli Liu,Xiyu Liu,Qiaoying Chen,Pan Wu,Jian He,Yongmei Li,Yongxiang Zhao,Ziqun Liu,Yan Zu,Yong Huang,Bing Wang
Immunotherapy has made encouraging progress in the field of cancer treatment. Among them, the programmed cell death-ligand 1 (PD-L1) antibody-mediated immunotherapy has stimulated the development of various carrier delivery systems. Inspired by related researchs, in this study, we prepare core-shell structured poly(lactide-co-glycolide) (PLGA) microcapsules as a drug delivery system through microfluidics technology, loaded with PD-L1 aptamers and chemotherapy drug docetaxel. The PD-L1 aptamer loaded in the nuclear layer binds to the PD-L1 molecule produced by tumor cells, blocking the immune checkpoint protein-1/programmed cell death-ligand 1 (PD-1/PD-L1) pathway. As a result, phagocytosis of tumor cells is promoted by using lipopolysaccharide (LPS) induced tumor associated macrophages. Furthermore, docetaxel in the shell is further released, inhibiting tumor cell growth as the PLGA microcapsules degrade. More importantly, the combination of PD-L1 aptamers and the chemotherapy drug docetaxel improved the immune response of the tumor. It showed significant anti-tumor activity and reduced systemic side effects in the melanoma model. At present, more and more nucleic acid aptamers as affinity reagents that can replace antibodies have been used to improve tumor treatment. Therefore, this therapeutic strategy provides more possibilities for tumor treatment by combining aptamer molecules with chemotherapy drugs when exploring more effective combination drugs.
研究领域:
癌症治疗
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药物递送系统
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免疫学
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制药学
✓ 已验证
产品关联
DOI
高影响因子
Advanced Therapeutics
·
2025
·
IF 2.6
Qi Tan,Yuwei Hu,Bo Wang,Songwei Tan,Yang Guan,Li Zhou,Qing Tang
Ulcerative colitis (UC) is a chronic inflammatory bowel disease with a need for more effective and less invasive treatment options. This study aimed to develop a targeted drug delivery system using hyperbranched polyglycidylglycerol-poly(lactic acid)-hydroxyacetic acid (HPG-PLGA)nanoparticles (NPs) loaded with baicalin (BN), a flavonoid with potent anti-inflammatory properties, to enhance therapeutic efficacy in UC. HPG-PLGA NPs are synthesized, characterized, and loaded with BN. The particle size, polydispersity index (PDI), encapsulation efficiency, and in vitro release profile of the NPs are evaluated. The in vivo biodistribution and therapeutic efficacy of the NPs are assessed in a dextran sulfate sodium-induced UC mouse model. The synthesized HPG-PLGA NPs demonstrated good stability and a controlled release of BN. In vivo studies showed significant accumulation of NPs in the inflamed colon, with a subsequent reduction in disease activity and inflammation markers. The treatment group exhibited lower levels of tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6 compared to the model group, indicating effective alleviation of inflammation. Furthermore, the NPs showed no significant toxicity to major organs. This study provides a promising approach for the development of targeted UC treatments, offering a potential clinical application by enhancing the bioavailability and specificity of BN to inflammatory sites.
研究领域:
药剂学
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纳米技术
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胃肠病学
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炎症性肠病
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药物递送系统
✓ 已验证
产品关联
DOI
高影响因子
Science of Advanced Materials
·
2019
·Vol. 11
·期 12
·1816-1824
·
IF 1.158
Qin Huihao,Zhang Wei,Luo Yi,Wei Yubo,Sun Shenglu,Chen Jingya
Polylactic acid glycolic acid (PLGA), a polymer material, is used as a shell and perfluorooctane (PFOB) as the core. Fe3O4@SiO2 nanoparticles are distributed in the shell to prepare a magnetic phase change multifunctional nano emulsion contrast agent
(Fe3O4@SiO2/PLGA/PFOB). The ultrasound, magnetic resonance imaging and CT imaging effects of the contrast agent on normal rat liver parenchyma are investigated. Methods: Single emulsification method is used to prepare Fe3O4@SiO2-loaded
polymer Fe3O4@SiO2/PLGA/PFOB nanoparticles encapsulated with PLGA. In addition, polymer Fe3O4@SiO2/PLGA nanoparticles loaded with Fe3O4@SiO2 nanoparticles, PLGA@PFOB nanoparticles coated with
PLGA and blank PLGA nanoparticles are prepared as experimental control group. Its surface morphology, internal structure, particle size, potential and other general characteristics are tested. RAW264.7 mouse mononuclear macrophages are cultured in vitro. Prussian blue staining is used
to observe macrophage phagocytosis after Fe3O4@SiO2/PLGA/PFOB contrast agent is added to incubate for 3 hours. MTT method is used to detect the effect of contrast agent on cell activity. The macrophage suspension engulfed with Fe3O4-PFOB
is examined by ultrasound, magnetic resonance and CT. The results showed that Fe3O4@SiO2/PLGA/PFOB is brown emulsion after being dissolved in double distilled water. Under the light microscope and scanning electron microscope, Fe3O4@SiO2/PLGA/PFOB
is spherical, with regular shape, uniform size, good dispersity and smooth surface. Macrophages are dependent on the phagocytosis of the contrast medium without affecting the activity of macrophages. Moreover, in vitro imaging experiments, compared with the control group, macrophages
phagocytized by Fe3O4@SiO2/PLGA/PFOB have obvious enhancement effects in ultrasound, magnetic resonance and CT imaging. In conclusion, Fe3O4@SiO2/PLGA/PFOB has good stability in vivo, can be engulfed by liver macrophages,
and can enhance ultrasound, magnetic resonance and CT imaging of liver parenchyma. It is a safe and effective multifunctional ultrasound contrast agent.
研究领域:
医学影像学
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材料科学
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生物医学工程
✓ 已验证
DOI
高影响因子
ADVANCES IN POLYMER TECHNOLOGY
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2020
·
IF 1.539
Lei Li,Yan Li,Cheng Miao,Rui Liu
This study was to explore the therapeutic effect and mechanism of puerarin (PUE) combined with PEGylated nanoparticles on a rat cerebral infarction cell model. In this context, PEG-PLGA/PUE nanoparticles were prepared by the thin-film hydration method, and the toxicity of PEG-PLGA/PUE nanoparticles to brain capillary endothelial cell (BCEC) was detected by MTT. The BCEC/TF cell model was obtained by induction of BCEC cells with TNF-α. The BCEC/TF cell model was identified by immunofluorescence; the protein expression was detected by western blotting; the expression level of miR-424 in cells was measured by RT-qPCR; the targeting relationship between miR-424 and PDCD4 was confirmed by dual-luciferase reporter assay. We found that PEG-PLGA/PUE nanoparticles prepared by the thin-film hydration method had uniform particle size, regular shape, and good stability and were not toxic to cells. The vWF was widely expressed in the cytoplasm in BCECs. The BCEC/TF cell model was obtained after TNF-α treatment, and tissue factor (TF) was widely expressed on the cell membrane of BCEC/TF cells. Furthermore, it was observed that the PEG-PLGA/PUE nanoparticles showed better therapeutic effect on the BCEC/TF cell model than PUE. PEG-PLGA/PUE nanoparticles and PUE inhibited the expression of PDCD4 protein by increasing the expression of miR-424 in BCEC/TF cells. In summary, the therapeutic effect of PEG-PLGA/PUE nanoparticles on the in vitro cell model of cerebral infarction is better than that of PUE. Moreover, PEG-PLGA/PUE inhibits the expression of PDCD4 protein by lowering the expression level of miR-424 in cells, thereby reducing the hazard of cerebral infarction.
研究领域:
药理学
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神经科学
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分子生物学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
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2023
·
IF 5
Fenglin Huang,Sisi Yang,Hao Wang,Peiwen Zhao,Bo Zhou,Bo Cheng,Siyan Dong,Jing Yang,Binbin Li,Xinyu Wang
Multi-functional drug-loaded microsphere system can overcome drug resistance and selectively transport drugs to tumor tissues, thus reducing the toxicity to normal tissues, and can achieve long-term effect through drug release, thus becoming a new way to treat tumor-related diseases. Poly (lactic-co-glycolic acid) PLGA/gelatin composite microspheres were prepared by an emulsion solvent evaporation technique. The microsphere shows that it has positive charge and pH response, which is more suitable for the weak acid environment of tumor and has certain targeting effect. At the same time, the scanning electron microscope showed that the surface was loose and rough, and the internal structure was porous, and the morphology was novel. In addition, UV spectrophotometer was used to test the drug loading rate and encapsulation efficiency of the microspheres. For smooth PLGA and PLGA/gelatin microspheres, the latter has better drug loading rate of 11.66% and encapsulation rate of 89.22%. The results showed that among pure paclitaxel , PLGA and PLGA/gelatin microspheres, the latter had the better than performance in the lethal rate of lung cancer cells and could achieve the goal of continuous lethal. Therefore, the preparation of porous drug-loaded microspheres in this study is pH responsive, and can achieve the goal of safe, targeted and efficient inhibition of cancer cell proliferation , and inspire the follow-up anti-cancer research.
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
International Journal of Nanomedicine
·
2023
·
IF 8
Baohua Li,Geng Lu,Wenbin Liu,Liqi Liao,Junfeng Ban,Zhufen Lu
Introduction The tight structure of the blood–brain barrier severely limits the level of drug therapy for central nervous system disorders. In this study, a novel composite delivery system combining nanocarrier and microneedle technology was prepared to explore the possibility of transdermal delivery of drugs to work in the brain.Methods Nanoparticle solutions containing paroxetine and rhodamine-B were prepared using PLGA as a carrier by the emulsification-solvent volatilization method. Then, they were mixed with hyaluronic acid and the PLGA nanoparticulate-based microneedle system (Rh-NPs-DMNs) was prepared by a multi-step decompression-free diffusion method. The particle size, zeta potential, and micromorphology of the nano solution were measured; the appearance, mechanical strength, dissolution properties, and puncture effect of the Rh-NPs-DMNs were evaluated; also, it was evaluated for in vivo live imaging properties and in vitro skin layer transport and distribution properties.Results The mean particle size of Rh-NPs was 96.25 ± 2.26 nm; zeta potential of 15.89 ± 1.97 mV; PDI of 0.120 ± 0.079. Rh-NPs-DMNs had a high needle content of 96.11 ± 1.27% and a tip height of 651.23 ± 1.28 μm, with excellent mechanical properties (fracture force of 299.78 ± 1.74 N). H&E skin tissue staining showed that Rh-NPs-DMNs produced micron-sized mechanical pores approximately 550 μm deep immediately after drug administration, allowing for efficient circulation of the drug; and the results of in vivo imaging showed that Rh-B NPs DMNs had a faster transport rate than Rh-B DMNs, with strong fluorescent signals in both brain (P<0.01) and hippocampus (P<0.05) 48 h after drug administration.Conclusion Nanoparticles can prolong blood circulation time and intracerebral retention time and have certain brain-targeting properties due to their excellent physical properties. The use of microneedle technology combined with nanocarriers provides new ideas for delivery systems for the treatment of central neurological diseases.
研究领域:
药剂学
·
神经科学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
LANGMUIR
·
2025
·
IF 3.9
Ruoxin Wei,Jiaze Dou,Yihui Wu,Jinjin Li,Lian Cen,Zhenhao Xi
Microsphere formulations represent a promising drug delivery system for proteins and peptides with short half-lives as they effectively mitigate drug degradation in vivo. This study aimed to develop poly(lactic-co-glycolic acid) (PLGA) microspheres loaded with leuprolide acetate (LA) using microfluidic technology and to investigate key factors that could have a significant effect on the LA encapsulation and loading. A glass capillary microfluidic device for a water-in-oil-in-water (W/O/W) emulsion system was developed. Gelatin (Gel) of varying concentrations was introduced in the internal aqueous phase, and different collecting solutions for W/O/W emulsions were investigated. The effect of the LA concentration in the inner phase was also explored. It was shown that LA-loaded PLGA microspheres (LA–PLGA–MS) by microfluidics were monodisperse with a uniform particle size of 80 μm and exhibited a distinguished core–shell structure. At a Gel concentration of 7.5 mg/mL, the microspheres reached a maximum encapsulation efficiency (EE) of 80.28% and a drug loading (DL) of 4.24%. The in vitro release could last for around 28 days. The DL of microspheres was found to be increased with the increase in LA concentration in the inner water phase. The incorporation of Gel within the inner water phase and the collecting solution with a suitable pH value were the main factors that affected the EE of microspheres. Briefly, LA–PLGA–MS could be successfully prepared and regulated using microfluidics and sustained LA release as monodispersed microsphere formulations. The developed technological strategy could provide a precise strategy and experimental reference for applications in delivery systems for water-soluble peptides and proteins.
研究领域:
药剂学
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生物医学工程
·
纳米技术
·
药物递送
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Biomaterials Science & Engineering
·
2021
·
IF 4.749
Jidong Dai,Xin Tan,Min Liang,Dandan Wei,Yinhua Tao,Pengfei Ren,Tianzhu Zhang
Poly(lactide-co-glycolide) (PLGA) has been widely used as a scaffold material for tissue engineering owing to its biocompatibility, biodegradability, and biosafety. However, lactic acid (LA) produced during PLGA degradation is prone to inflammation, which is a shortcoming that must be avoided. To this end, crystalline PLGA-PEG was synthesized here for the first time. To make the crystalline PLGA-PEG more suitable for tissue engineering, porous crystalline PLGA-PEG was prepared via the swelling behavior during recrystallization annealing. The structure and properties of the porous crystalline PLGA-PEG were confirmed by SEM, POM, and XRD. Furthermore, the swelling behavior of different PEG molecular weights was studied, and the cell viability test and alkaline phosphatase activity test showed that PLGA-PEG has good biocompatibility. Such a porous crystalline PLGA-PEG will make PLGA have a broader application prospect in bone repair.
研究领域:
材料科学
·
生物医学工程
·
组织工程
✓ 已验证
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2023
·
IF 8
Chenchen Bi,Aiping Wang,Yongchao Chu,Sha Liu,Hongjie Mu,Wanhui Liu,Zimei Wu,Kaoxiang Sun,Youxin Li
Sustainable and safe delivery of brain-targeted drugs is highly important for successful therapy in Parkinson’s disease (PD). This study was designed to formulate biodegradable poly(ethylene glycol)–poly(lactic-co-glycolic acid) (PEG-PLGA) nanoparticles (NPs), which were surface-modified with lactoferrin (Lf), for efficient intranasal delivery of rotigotine to the brain for the treatment of PD. Rotigotine NPs were prepared by nanoprecipitation, and the effect of various independent process variables on the resulting properties of NPs was investigated by a Box–Behnken experimental design. The physicochemical and pharmaceutical properties of the NPs and Lf-NPs were characterized, and the release kinetics suggested that both NPs and Lf-NPs provided continuous, slow release of rotigotine for 48 h. Neither rotigotine NPs nor Lf-NPs reduced the viability of 16HBE and SH-SY5Y cells; in contrast, free rotigotine was cytotoxic. Qualitative and quantitative cellular uptake studies demonstrated that accumulation of Lf-NPs was greater than that of NPs in 16HBE and SH-SY5Y cells. Following intranasal administration, brain delivery of rotigotine was much more effective with Lf-NPs than with NPs. The brain distribution of rotigotine was heterogeneous, with a higher concentration in the striatum, the primary region affected in PD. This strongly suggested that Lf-NPs enable the targeted delivery of rotigotine for the treatment of PD. Taken together, these results demonstrated that Lf-NPs have potential as a carrier for nose-to-brain delivery of rotigotine for the treatment of PD.
研究领域:
药剂学
·
神经科学
·
药物递送系统
✓ 已验证
DOI
PubMed
高影响因子
Materials Science & Engineering C-Materials for Biological Applications
·
2019
·
IF 4.959
Xiangsheng Wang,Ai Ai,Ziyou Yu,Mingwu Deng,Wei Liu,Guangdong Zhou,Wei Li,Wenjie Zhang,Yilin Cao,Xiansong Wang
Biodegradable scaffolds play an important role in tissue engineering, and appropriate degradation and resorption rates of these scaffolds are necessary to accommodate tissue growth. Synthetic polymers are frequently used because of their ease of production, good biocompatibility and controllable degradation rates. However, monitoring the degradation of these polymers in vivo by a noninvasive approach remains limited. In this study, we designed a composite scaffold by labeling poly(lactic-co-glycolic acid) (PLGA) with gold nanoclusters (Au NCs), which were used for tracking in vivo degradation through dual-modal fluorescence/computed tomography (CT) imaging. The diameter of the Au NCs was approximately 2.5 nm, and the emission peak was at a wavelength of 700 nm. After labeling PLGA with the Au NCs, the fluorescence intensity of the Au NC/PLGA composite scaffold reached 9.0 × 10 9 (p/s/cm 2 /sr)/(μW/cm 2 ), and the CT density of the scaffold increased to 200 HU. After the composite scaffold was implanted subcutaneously into nude mice, a continuous decrease in the fluorescence signal and CT value was observed. The mean fluorescence intensity was 8.3 × 10 9 , 3.17 × 10 9 , 2.26 × 10 9 , 2.11 × 10 9 , and 1.82 × 10 9 (p/s/cm 2 /sr)/(μW/cm 2 ) from the first week to the fifth week, respectively. The mean CT value changed from 222.6 to 185.9, 149.1, 112.5, and 55.2 (Hounsfield unit, HU) at the different timepoints. Compared with the change in the fluorescence intensity, the change in the CT value was similar to the change in the weight, and the Pearson correlation coefficient between the change in the CT value and weight was 0.8626. Furthermore, the structure and morphology of the scaffolds at different timepoints were analyzed by three-dimensional (3-D) reconstruction. This novel method of noninvasive dynamic monitoring of biodegradable polymers in vivo provides insight into choosing suitable biomaterials for tissue engineering and regenerative medicine.
研究领域:
生物材料学
·
医学影像学
·
组织工程学
✓ 已验证
DOI
PubMed
高影响因子
Biomaterials Advances
·
2024
·
IF 5.5
Xianli Wang,Xiaoyu Li,Nannan Gu,Yi Shao,Yunfei Guo,Yongji Deng,Chenglin Chu,Feng Xue,Liqu Huang,Li Tao,Jing Bai
Biodegradable Mg/polymer composite fibers offer a promising therapeutic option for tissue injury because of bioactive Mg 2+ and biomimetic microstructure. However, current studies are limited to the contribution of Mg 2+ and the single microstructure. In this study, we designed Mg/poly (lactic- co -glycolic acid) (Mg/PLGA) composite microfibers that significantly enhanced angiogenesis and tissue regeneration synergistically by Mg 2+ and self-sculptured microstructure, due to spontaneous in situ microphase separation in response to the weakly alkaline microenvironment. Our composite microfiber patch exhibited superior performance in the adhesion, spreading, and angiogenesis functions of human umbilical vein endothelial cells (HUVECs) due to the joint contribution of the hierarchically porous microstructure and Mg 2+ . Genomics and proteomics analyses revealed that the Mg/PLGA composite microfibers activated the cell focal adhesion and angiogenesis-related signaling pathways. Furthermore, the repair of typical soft tissue defects, including refractory urethral wounds and easily healed skin wounds, validated that our Mg/PLGA composite microfiber patch could provide favorable surface topography and ions microenvironment for tissue infiltration and accelerated revascularization. It could cause rapid urethral tissue regeneration and recovery of rabbit urethral function within 6 weeks and accelerate rat skin wound closure within 16 days. This work provides new insight into soft tissue regeneration through the bioactive alkaline substance/block copolymer composites interactions.
研究领域:
生物材料学
·
组织工程学
·
再生医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
·
2012
·
IF 3.212
Jianian Chen,Shaoshun Li,Qi Shen
Dual- and multi-functional drug delivery systems , especially ligand-modified nanoparticles (NPs) loaded with chemotherapeutic agents are paid much attention to due to their excellent behavior in vitro and in vivo . Bifunctional NPs (BF-NPs), which were based on PLGA–PEG and modified with folic acid and cell penetrating peptide R 7 simultaneously, were developed. BF-NPs loaded with vincristine sulfate (VCR) were prepared via the water–oil–water emulsion solvent evaporation method. BF-NPs showed favorable particle size and zeta potentials , promising drug loading and entrapment efficiency. The release of VCR from BF-NPs exhibited a biphase release manner. Cellular uptake of BF-NPs was found to be higher than that of the NPs merely modified by folic acid or R 7 . In vitro cytotoxicity, cell apoptosis and cell cycle arrest studies also revealed that BF-NPs were more potent than those of the NPs merely modified by folic acid or R 7 . Therefore, the results demonstrated that BF-NPs developed in this study could be a potential vehicle for delivering chemotherapeutic agents such as VCR and breast cancer therapy.
研究领域:
药学
·
纳米技术
·
癌症研究
✓ 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）