Journal of Huazhong University of Science and Technology-Medical Sciences
·
2012
·Vol. 32
·期 4
·563-570
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IF 0.385
Tian Zhichao,Zhu Yuanli,Qiu Jinjun,Guan Hanfeng,Li Liangyu,Zheng Shouchao,Dong Xuehai,Xiao Jun
A novel unsaturated polyphosphoester (UPPE) was devised in our previous research, which is a kind of promising scaffold for improving bone regeneration. However, the polymerization process of UPPE scaffolds was unfavorable, which may adversely affect the bioactivity of osteoinductive molecules added if necessary, such as recombinant human bone morphogenetic protein-2 (rhBMP2). The purpose of this study was to build a kind of optimal scaffold named UPPE-PLGA-rhBMP2 (UPB) and to investigate the bioactivity of rhBMP2 in this scaffold. Furthermore, the cytotoxicity and biocompatibility of UPB scaffold was assessed in vitro . A W1/O/W2 method was used to fabricate PLGA-rhBMP2 microspheres, and then the microspheres were added to UPPE for synthesizing UPB scaffold. The morphological characters of PLGA-rhBMP2 microspheres and UPB scaffolds were observed under the scanning electron microscopy and laser scanning confocal microscopy. The cumulative release of UPB scaffolds was detected by using ELISA. The cytotoxicity and biocompatibility of UPB scaffolds were evaluated through examining the adsorption and apoptosis of bone marrow stromal cells (bMSCs) seeded on the surface of UPB scaffolds. The bioactivity of rhBMP2 in UPB scaffolds was assessed through measuring the alkaline phosphates (ALP) activity in bMSCs seeded. The results showed that UPB scaffolds sequentially exhibited burst and sustained release of rhBMP2. The cytotoxicity was greatly reduced when the scaffolds were immersed in buffer solution for 2 h. bMSCs attached and grew on the surface of soaked UPB scaffolds, exerting well biocompatibility. The ALP activity of bMSCs seeded was significantly enhanced, indicating that the bioactivity of rhBMP2 remained and still took effect after the unfavorable polymerization process of scaffolds. It was concluded that UPB scaffolds have low cytotoxicity, good biocompatibility and preserve bioactivity of rhBMP2. UPB scaffolds are promising in improving bone regeneration.
研究领域:
材料科学
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生物医学工程
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组织工程
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2022
·
IF 5.988
Nana Li,Lei Dong,Yuanyuan Shen,Yongling Wang,Liansheng Chang,Hongwei Wu,Yuqiao Chang,Menghao Li,Dan Li,Zhaoyi Li,Mei He,Cheng Li,Yao Wei,Haiqin Xie,Feng Wang
In recent years, studies have shown a close relationship between cardiomyocyte death and ferroptosis. Clioquinol (CQ) can inhibit ferroptosis. Porous lipid-poly (lactic-co-glycolic acid) (PLGA) microbubbles (MBs) were prepared by double emulsification (W 1 /O/W 2 ) using 1,2-dioctadecanoyl-sn-glycero-3-phophocholine and PLGA as raw materials. Porous lipid-PLGA MBs were used as carriers to prepare CQ/PLGA MBs containing CQ. CQ/PLGA had the advantages of high drug loading, good biocompatibility, and sustained release. Our results showed that CQ/PLGA improved the effect of CQ and reduced its cytotoxicity. Under low-frequency ultrasound with certain parameters, CQ/PLGA showed steady-state cavitation, which increased the membrane permeability of mouse cardiomyocyte HL-1 to a certain extent and further prevented the process of ferroptosis in mouse cardiomyocyte HL-1.
研究领域:
心脏病学
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药学
·
生物医学工程
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DOI
PubMed
高影响因子
Research
·
2024
·
IF 8.5
Ping Li,Yang Yang,Yifei Wang,Jingbin Zheng,Fengyang Chen,Mengmeng Jiang,Chon-Kit Chou,Weihong Cong,Zongjin Li,Xin Chen
High levels of tumor necrosis factor receptor type II (TNFR2) are preferentially expressed by immunosuppressive CD4 + Foxp3 + regulatory T cells (T regs ), especially those present in the tumor microenvironment, as initially reported by us. There is compelling evidence that targeting TNFR2 markedly enhances antitumor immune responses. Furthermore, a broad spectrum of human cancers also expresses TNFR2, while its expression by normal tissue is very limited. We thus hypothesized that TNFR2 may be harnessed for tumor-targeted delivery of chemotherapeutic agents. In this study, we performed a proof-of-concept study by constructing a TNFR2-targeted PEGylated poly(dl-lactic-co-glycolic acid) (PLGA-PEG) nanodrug delivery system [designated as TNFR2-PLGA-ADR (Adriamycin)]. The results of in vitro study showed that this TNFR2-targeted delivery system had the properties in cellular binding and cytotoxicity toward mouse colon cancer cells. Further, upon intravenous injection, TNFR2-PLGA-ADR could efficiently accumulate in MC38 and CT26 mouse colon tumor tissues and preferentially bind with tumor-infiltrating T regs . Compared with ADR and ISO-PLGA-ADR, the in vivo antitumor effect of TNFR2-PLGA-ADR was markedly enhanced, which was associated with a decrease of TNFR2 + T regs and an increase of IFNγ + CD8 + cytotoxic T lymphocytes in the tumor tissue. Therefore, our results clearly show that targeting TNFR2 is a promising strategy for designing tumor-specific chemoimmunotherapeutic agent delivery system.
研究领域:
肿瘤学
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药学
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免疫学
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DOI
PubMed
高影响因子
RSC Advances
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2016
·Vol. 6
·期 34
·28331-28342
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IF 3.289
Lu Wang,Xi Xie,Di Liu,Xiao-Bin Fang,Peng Li,Jian-Bo Wan,Cheng-Wei He,Mei-Wan Chen
Reduction-sensitive micelles with crosslinked cores were developed to load the lipophilic chemotherapeutic drug docetaxel (DTX) in order to overcome the issues of toxicity, water insolubility, and rapid metabolism of DTX. These DTX-loaded micelles (MM(DTX/Crosslink)) provide efficient incorporation and sustained release of DTX. Using independently synthesized LA–PLGA–TPGS and DSPE–PEG polymers as vehicles, MM(DTX/Crosslink) was found to be reduction-responsive, and possessed desirable drug entrapment efficiency (84.17 ± 1.15%) and drug loading efficiency (6.21 ± 0.07%). The MM(DTX/Crosslink) quickly dissociated under reduction conditions that mimicked the reductive intracellular environment, suggesting that it can rapidly release the encapsulated DTX in vitro. Furthermore, to target MM(DTX/Crosslink) to tumors for cancer therapy, iRGD was conjugated to the surface of MM(DTX/Crosslink). The iRGD-MM(DTX/Crosslink) micelles significantly increased the cellular uptake of DTX and inhibited cell proliferation, compared to the micelles without iRGD modification. Moreover, the iRGD-MM(DTX/Crosslink) micelles presented enhanced antitumor effects based on the analyses of apoptosis and cell cycle arrest. The micelles developed in this work may constitute a stable, efficient, and powerful system to deliver DTX into cancer cells.
研究领域:
药剂学
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肿瘤学
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生物材料学
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产品关联
DOI
高影响因子
JOURNAL OF PHARMACEUTICAL SCIENCES
·
2024
·
IF 3.7
Anqi Wang,Yuanyuan Liu,Wugui Xiong,Wei Li,Jin Li,Zhiqiang Yang,Zhongtao Zou,Yinjia Luo,Zhoujiang Chen,Hanmei Li,Chi Teng Vong,Liang Zou
Honokiol (HNK) is one of the bioactive ingredients from the well-known Chinese herbal medicine Magnolia officinalis , and its research interests is rising for its extensive pharmacological activities, including novel therapeutic effect on ulcerative colitis (UC). However, further application of HNK is largely limited by its unique physicochemical properties, such as poor water solubility, low bioavailability, as well as unsatisfied targeting efficacy for inflammatory lesions. In this study, we constructed galactosylation modified PLGA nanoparticles delivery system for efficient target delivery of HNK to the colitic lesions, which could lay a research foundation for the deep development of HNK for the treatment of UC. D-galactose was grafted by chemical coupling reactions with PLGA to prepare Gal-PLGA, which was used as a carrier for HNK (Gal-PLGA@HNK nanoparticles (NPs)). To improve the colon targeting efficiency by oral administration of the NPs, Eudragit S100 was used for wrapping on the surface of Gal-PLGA@HNK NPs (E/Gal-PLGA@HNK NPs). Our results showed that the encapsulation efficiency and drug loading capacity of E/Gal-PLGA@HNK NPs were 90.72 ± 0.54% and 8.41 ± 0.02%, respectively. Its average particle size was 242.24 ± 8.42 nm, with a PDI value of 0.135 ± 0.06 and zeta-potential of -16.83 ± 1.89 mV. The release rate of HNK from E/Gal-PLGA@HNK NPs was significantly decreased when compared with that of free HNK in simulated gastric and intestinal fluids, which displayed a slow-releasing property. It was also found that the cellular uptake of E/Gal-PLGA@HNK NPs was significantly increased when compared with that of free HNK in RAW264.7 cells, which was facilitated by D-galactose grafting on the PLGA carrier. Additionally, our results showed that E/Gal-PLGA@HNK NPs significantly improved colonic atrophy, body weight loss, as well as reducing disease activity index (DAI) score and pro-inflammatory cytokine levels in UC mice induced by DSS. Besides, the retention time of E/Gal-PLGA@HNK NPs in the colon was significantly increased when compared with that of other preparations, suggesting that these NPs could prolong the interaction between HNK and the injured colon. Taken together, the efficiency for target delivery of HNK to the inflammatory lesions was significantly improved by galactosylation modification on the PLGA carrier, which provided great benefits for the alleviation of colonic inflammation and injury in mice.
研究领域:
药学
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纳米技术
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药物递送系统
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炎症性肠病
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOSCIENCE AND NANOTECHNOLOGY
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2016
·Vol. 16
·期 6
·5569-5576
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IF 1.338
Li Qinqin,Li Chenglin,Tong Weijun
Here, a novel poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles (NPs) for magnetic resonance (MR) and fluorescence imaging was developed for cell imaging. PLGA NPs loaded with fluorescent dye Nile red (NR) and surface-coated with poly(ethyleneimine) (PEI) were produced in a single
step nanoprecipitation process. Diethylenetriamine pentaacetic dianhydride (DTPA) was conjugated to PLGA/NR@PEI NPs through amidation reaction between –COOH of DTPA and –NH2 of PEI, which can chelate gadolinium (Gd3+) as an MR imaging contrast agent. The PLGA/NR@PEI-DTPA-Gd
NPs exhibited a uniform particle size of ∼200 nm and were stable in culture medium. These NPs had a high T
1 relaxivity (R
1) of 28.36 mM−1S−1. They did not introduce serious cytotoxicity against A549 lung cancer cells.
Furthermore, fluorescence and MR imaging studies on A549 lung cancer cells in vitro revealed that PLGA/NR@PEI-DTPA-Gd NPs can serve as an efficient fluorescence/MR dual-modality imaging nanoprobe.
研究领域:
纳米技术
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生物医学工程
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材料科学
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医学成像
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癌症研究
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DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2016
·
IF 4.32
Yunzhu Qian,Hanbang Chen,Yang Xu,Jianxin Yang,Xuefeng Zhou,Feimin Zhang,Ning Gu
Constructing biomimetic structure and incorporating bioactive molecules is an effective strategy to achieve a more favorable cell response. To explore the effect of electrospinning (ES) nanofibrous architecture and collagen I (COL I)-incorporated modification on tuning osteoblast response, a resorbable membrane composed of poly(lactic-co-glycolic acid)/poly(caprolactone) (PLGA/PCL; 7:3 w/w) was developed via ES. COL I was blended into PLGA/PCL solution to prepare composite ES membrane. Notably, relatively better cell response was delivered by the bioactive ES-based membrane which was fabricated by modification of 3,4-dihydroxyphenylalanine and COL I. After investigation by field emission scanning electron microscopy, Fourier transform infrared spectroscopy, contact angle measurement, and mechanical test, polyporous three-dimensional nanofibrous structure with low tensile force and the successful integration of COL I was obtained by the ES method. Compared with traditional PLGA/PCL membrane, the surface hydrophilicity of collagen-incorporated membranes was largely enhanced. The behavior of mouse preosteoblast MC3T3-E1 cell infiltration and proliferation on membranes was studied at 24 and 48 hours. The negative control was fabricated by solvent casting. Evaluation of cell adhesion and morphology demonstrated that all the ES membranes were more favorable for promoting the cell adhesion and spreading than the casting membrane. Cell Counting Kit-8 assays revealed that biomimetic architecture, surface topography, and bioactive properties of membranes were favorable for cell growth. Analysis of β1 integrin expression level by immunofluorescence indicated that such biomimetic architecture, especially COL I-grafted surface, plays a key role in cell adhesion and proliferation. The real-time polymerase chain reaction suggested that both surface topography and bioactive properties could facilitate the cell adhesion. The combined effect of biomimetic architecture with enhanced surface activity by 3,4-dihydroxyphenylalanine-assisted modification and COL I incorporation of PLGA/PCL electrospun membranes could successfully fill osteogenic defects and allow for better cell proliferation and differentiation.
研究领域:
生物材料
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组织工程
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细胞生物学
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材料科学
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产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF MEDICAL RESEARCH
·
2025
·Vol. 30
·期 1
·1-14
·
IF 3.4
Wang Xiu,Du Wentao,Wang Yunyun,Khan Ahsan Riaz,Zhang Haijun
Objective This study aims to design and fabricate a leadless pacemaker (LPM) electrode loaded with rapamycin (RAPA)–poly(lactic-co-glycolic acid) (PLGA) drug sustained-release system to reduce the local fibrous tissue proliferation after LPM implantation, reduce local bioelectrical impedance, and facilitate the safe extraction of LPM after use. Methods We fabricated an LPM electrode loaded with the RAPA-PLGA drug-sustained-release system and carried out in vitro and in vivo experiments to verify its effect. Results A scanning electron microscope showed that the LPM electrode cavity was loaded with the RAPA-PLGA drug’s sustained-release system. The energy-dispersive spectrometer showed that the LPM electrode had RAPA and PLGA-related elements. The average drug loading rate of the drug sustained-release system was (51.02% ± 2.66) %, and the encapsulation rate was (85.04% ± 4.43%). The RAPA loaded in the electrode chamber was about (337.83 ± 53.66)μg. In vitro release results show that the LPM electrode loaded with RAPA–PLGA can continue to release for 44 days. In vitro cell inhibition experiments showed that the drug-loaded electrode group had an obvious inhibitory effect on fibroblasts, and the difference between the groups was significant ( p < 0.05). In vivo experiments showed that the local bioelectrical impedance of the drug-loaded electrode group is lower than that of the control group, with a difference between groups with statistical significance ( p < 0.05). The histopathological analysis of tissue sections from the site of (LPM electrode implantation revealed reduced fibrous tissue hyperplasia in the drug-loaded electrode group compared to the control group. Additionally, H&E staining indicated that the implantation of drug-loaded electrodes did not induce abnormal alterations in the liver, heart, spleen, lung, or kidney tissues. Conclusion The LPM electrode loaded with RAPA–PLGA demonstrates significant, sustained drug release and anti-proliferative effects in vitro. This drug-loaded electrode has been deemed safe for implantation in animal models. It can effectively inhibit local fibrous tissue proliferation and reduce local bioelectrical impedance, offering a technical strategy to prolong the in vivo functionality of LPMs and enhance clinical procedures.
研究领域:
医学工程
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药理学
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心血管病学
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DOI
PubMed
高影响因子
Water Biology and Security
·
2023
·
IF 0
Chaolin Jiang,Xingchen Huo,Lingjie Tang,Meidi Hu,Chunrong Yang,Daji Luo,Jianguo Su
Grass carp hemorrhagic disease caused by grass carp reovirus (GCRV) results in significant economic losses to the global grass carp aquaculture industry. Oral vaccination is an ideal choice for disease precaution in aquaculture. However, oral vaccine can be degraded in the gut. Therefore, the selection of loading materials is essential. In this study, the S6 and S7 fragments (encoding the outer capsid protein VP4 and fibronectin VP56 of GCRV) and grass carp interferons (IFNs), including IFN1, IFN3, and IFNγ2 were used to create DNA vaccines and adjuvants based on pcDNA3.1, respectively. The oral DNA vaccine was encapsulated in poly(lactic-co-glycolic acid) (PLGA) and polyvinyl alcohol (PVA) with IFNs. The PLGA-PVA (PP) nano-microspheres were prepared by double emulsion-solvent evaporation technique. Using transmission electron microscopy and dynamic light scattering assays, it was determined the vaccines had a spherical structure with uniform particle size (643.5 ± 35.3 nm). The nano-microspheres possessed excellent encapsulation efficiency (81.6 ± 2.6%) and loading rate (0.54 ± 0.02%), and simultaneously exhibited negligible hemolytic activity and cell toxicity. The protection rate and tissue viral loads post-GCRV challenge in grass carp were assessed. The oral PP nano-microsphere with pVP4 + pIFN1 (PP41) vaccine increased protection rate by 44% compared with the control group and was correlated with relatively low viral loads in the spleen, head kidney, and hindgut. Further, three crucial serum biochemical indexes, total superoxide dismutase (TSOD), complement C3 (C3), and lysozyme (LZM), were also dramatically increased. Furthermore, mRNA expressions of representative immune-related genes (IgM, IFN1, IFNγ2, MHC-Ⅰ, and CD8α) in the head kidney and spleen were significantly enhanced. In addition, mRNA expression of IgT was significantly boosted in the hindgut. The results indicate that DNA vaccine capsulated with PP is effective against GCRV infection. The present study provides insights into a prospective strategy for oral vaccine development in aquaculture.
研究领域:
水产养殖
·
免疫学
·
病毒学
·
兽医学
✓ 已验证
DOI
International Journal of Nanomedicine
·
2016
·
IF 4.32
Yu Xin,Tie Liu,Chenlong Yang
We have prepared novel poly(d,l-lactide-co-glycolide) (PLGA) lipid nanoparticles (PNPs) that covalently conjugate folic acid (FA) and indocyanine green (ICG), in addition to encapsulating resveratrol (RSV) (FA-RSV/ICG-PLGA-lipid NPs, abbreviated as FA-RIPNPs); these nanoparticles have been developed for simultaneous targeted delivery of anticancer drug and fluorescence imaging. The FA-RIPNPs, with an average particle size of 92.8±2.1 nm, were prepared by a facile self-assembly-and-nanoprecipitation method, and they showed excellent stability and biocompatibility characteristics. The FA-RIPNPs exhibited an RSV encapsulation efficiency of approximately 65.6%±4.7% and a maximum release ratio of 78.2%±4.1% at pH 5.0 and 37°C. Confocal fluorescence images showed that FA-RIPNPs may facilitate a high cellular uptake via FA receptor-mediated endocytosis. Furthermore, FA-RIPNPs (containing 50 μg/mL RSV) induced a 81.4%±2.1% U87 cell inhibition rate via apoptosis, a value that proved to be higher than what has been shown for free RSV (53.1%±1.1%, equivalent RSV concentration). With a formulated polyethylene glycol (PEG) shell around the PLGA core, FA-RIPNPs prolonged the blood circulation of both free RSV and ICG, which approximately increased 6.96- and 39.4-fold (t1/2), respectively. Regarding FA-RIPNP use as a near-infrared probe, in vivo fluorescence images indicated a highly efficient accumulation of FA-RIPNPs in the tumor tissue, which proved to be approximately 2.8- and 12.6-fold higher than the RIPNPs and free ICG, respectively. Intravenous injection of FA-RIPNPs into U87 tumor-bearing mice demonstrated the best tumor inhibition effect for all tested drugs, including free RSV and RIPNPs, with no relapse, showing high biocompatibility and with no significant systemic in vivo toxicity over the course of the treatment (1 month). The results obtained demonstrate the versatility of the NPs, featuring stable fluorescence and tumor-targeting characteristics, with promising future applications in cancer therapy.
研究领域:
药剂学
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肿瘤学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2022
·
IF 5.062
Luyao Huang,Shengjie Wang,Zongning Yin
Therapeutic proteins/peptides face severe stability impairment in biotechnology drug delivery systems prepared by the W/O/W solvent evaporation method. Screening of protein stabilizers for poly (D, l -lactide-co-glycolide) (PLGA) nanoparticles can improve the low encapsulation efficiency and undesirable release behavior of proteins caused by PLGA carriers, which is a crucial step to achieve a high proportion of continuous release of encapsulated protein in the target time and give full play to the therapeutic effect. Therefore, model proteins were selected for stability testing to simulate the specific destabilization pathways. Through the comprehensive study of protein conformation, recovery rate, encapsulation rate, and drug release behavior, the effects of additives on the stability of protein were synthetically characterized, and their action links and mechanisms were also further studied. The results showed that different denaturation environments were intertwined during the preparation and release of peptide-loaded NPs, jointly inducing protein denaturation and incomplete release behavior. After optimization with stabilizers, urea and lactose increased the encapsulation efficiency of proteins to more than 95% (P < 0.001). Except for the P188 , all other stabilizers showed great potential for optimizing the release and stability of the encapsulated protein as a whole, increasing the release proportion of protein from 44% to 60 %-75% (P < 0.0001). The improvement of the drug release curve demonstrated the long-term stabilizing effect of the above-mentioned co-solubilizing additives on the therapeutic protein.
研究领域:
药学
·
生物技术
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纳米技术
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药物递送系统
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产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2019
·
IF 4.213
Jiaxin Liu,Shuang Li,Ge Li,Xiang Li,Changhui Yu,Zhijiang Fu,Xiangyu Li,Lesheng Teng,Youxin Li,Fengying Sun
Bevacizumab, a vascular endothelial growth factor (VEGF)-targeting drug, is widely used as an off-label therapeutic for age-related macular degeneration (AMD). To reduce the monthly administration frequency, this study investigated microspheres comprising a poly( d , l -lactide-co-glycolide)/poly(cyclohexane-1,4-diyl acetone dimethylene ketal) (PLGA/PCADK) blend that could be loaded with bevacizumab-dextran particles using solid-in-oil-in-water (S/O/W) emulsification. Control microspheres were also prepared through water-in-oil-in-water (W/O/W) emulsification. The structural stability of bevacizumab in the polymer monomers was analyzed using dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), size exclusion chromatography (SEC-HPLC), circular dichroism (CD) and fluorescence spectroscopy. Subsequently, microspheres were prepared and evaluated in terms of their morphology, encapsulation efficiency and release behavior. PLGA/PCADK microspheres prepared by the S/O/W method with <20% PCADK showed a smooth spherical structure with a uniform distribution of bevacizumab. The microspheres exhibited a release behavior comprising a slight initial burst and an increasing total release over 50 days both in vitro and in vivo . Additionally, the microspheres were well tolerated by ocular tissue. Finally, a chorioallantoic membrane (CAM) assay revealed that the bioactivity of bevacizumab was retained by PCADK. In conclusion, these results suggest the potential for bevacizumab-loaded PLGA/PCADK microspheres prepared by the S/O/W method as a means of intravitreal therapy for ocular diseases.
研究领域:
药物学
·
眼科学
·
药物递送系统
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）