International Journal of Nanomedicine
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2023
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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
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神经科学
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药物递送系统
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DOI
PubMed
高影响因子
ADVANCES IN POLYMER TECHNOLOGY
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2020
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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
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产品关联
DOI
高影响因子
CHEMICAL ENGINEERING SCIENCE
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2024
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IF 4.1
Wang Yao,Zhikai Liu,Letao Guo,Shirong Song,Mei Yang,Guangwen Chen
A robust microreactor with a sudden expansion structure was employed to facilitate controllable mixing with a mixing time ranging from 5.3 to 225.8 ms for water-acetonitrile mixing. Using this well-established mixing setup, a comprehensive investigation was conducted to analyze the inherent effects of various experimental variables on the size of PEG-PLGA NPs during nanoprecipitation. A consistent observation was that the size of PEG-PLGA NPs decreased as the mixing time decreased, ultimately reaching a limited size that no longer changed with the mixing time. This trend led to the classification of the nanoparticle formation process into slow and fast mixing stages. In the fast mixing stage, polymer concentration had minimal impact on particle size, while the anti-solvent to solvent flow rate ratio, solvent pair, and salt concentration influenced particle size by altering the solution environment. Lastly, the smallest attainable particle sizes of PEG-PLGA NPs under various experimental variables were revealed.
研究领域:
化学工程
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材料科学
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纳米技术
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产品关联
DOI
高影响因子
JOURNAL OF BIOMATERIALS APPLICATIONS
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2023
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IF 2.9
Weiqian Wu,Ruilai Liu,Jiahao Guo,Zhihuan Hu,Chenjing An,Yan Zhang,Tengyuan Liu,Lian Cen,Yukun Pan
The high hydrophobicity and low oral availability of immunosuppressive drug, rapamycin, seriously limit its application. It was thus aimed to develop a PEG-PLGA based nano-loading system for rapamycin delivery to achieve improved bioavailability with sustained effects via a novel microfluidic chip and manipulation of the hydrophobic PLGA chain length. PDMS based microfluidic chip with Y shape was designed and PEG-PLGA polymers with different PLGA chain length were used to prepare rapamycin nano-delivery systems. Dendritic cells were selected to evaluate the immunosuppressive effect of the nanoparticles including cytotoxicity assay, dendritic cell activation, and cytokine levels. The effects of different PEG-PLGA nanoparticles on the immunomodulatory properties were finally compared. It was shown that PEG-PLGA could be successfully used for rapamycin encapsulation via microfluidics to obtain nano-delivery systems (Rapa&P-20 k, Rapa&P-50 k and Rapa&P-95 k) ranging from 100 nm to 116 nm. The encapsulation efficiency was ranged from 69.70% to 84.55% and drug loading from 10.45% to 12.68%. The Rapa&P-50 k (PLGA chain length: 50 k) could achieve the highest drug loading (DL) and encapsulation efficiency (EE) as 12.68% and 84.55%. The encapsulated rapamycin could be gradually released from three nanoparticles for more than 1 month without any noticeable burst release. The Rapa & P nanoparticles exhibited enhanced immunosuppressive effects over those of free rapamycin as shown by the expression of CD40 and CD80, and the secretion of IL-1β, IL-12 and TGF-β1. Rapa&P-50 k nanoparticles could be the optimal choice for rapamycin delivery as it also achieved the most effective immunosuppressive property. Hence, this study could provide an efficient technology with superior manipulation to offer a solution for rapamycin delivery and clinical application.
研究领域:
药学
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纳米技术
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免疫学
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药物递送系统
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DOI
PubMed
高影响因子
International Journal of Nanomedicine
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2022
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IF 7.033
Zhengyue Kang,Min Yang,Xiaoling Feng,Hongjian Liao,Zhifei Zhang,Yonghong Du
Purpose Triple negative breast cancer (TNBC) is challenging for effective remission due to its very aggressive, extremely metastatic and resistant to conventional chemotherapy. Herein, a multifunctional theranostic nanoparticle was fabricated to enhance tumor targeted imaging and promote focused ultrasound (FUS) ablation and chemotherapy and sonodynamic therapy (SDT). A multi-modal synergistic therapy can improve the therapeutic efficacy and prognosis of TNBC.Methods AS1411 aptamer modified PEG@PLGA nanoparticles encapsulated with perfluorohexane (PFH) and anti-cancer drug doxorubicin (DOX) were constructed (AS1411-DOX/PFH-PEG@PLGA) to enhance tumor targeted imaging to guide ablation and synergistic effect of FUS/chemotherapy. FUS was utilized to trigger the co-release of doxorubicin and simultaneously PFH phase transition and activate DOX for SDT effect. The physicochemical, phase-changeable imaging capability, biosafety of nanoparticles and multi-mode synergistic effects on growth of TNBC were thoroughly evaluated in vivo and in vitro.Results The synthesized AS1411-DOX/PFH-PEG@PLGA (A-DPPs) nanoparticles are uniformly round with an average diameter of 306.03 ± 5.35 nm and the zeta potential of −4.05 ± 0.13 mV, displaying high biosafety and FUS-responsive drug release in vitro and in vivo. AS1411 modified NPs specifically bind to 4T1 cells and elevate the ultrasound contrast agent (UCA) image contrast intensity via PFH phase-transition after FUS exposure. Moreover, the combined treatment of A-DPPs nanoparticles with FUS exhibited significantly higher apoptosis rate, stronger inhibitory effect on 4T1 cell invasion in vitro, induced more reactive oxygen species (ROS), and enhanced anti-tumor effect compared to a single therapy (p < 0.05). Additionally, the joint strategy resulted in more intense cavitation effect and larger ablated areas and reduced energy efficiency factor (EEF) both in vitro and in vivo.Conclusion The multifunctional AS1411-DOX/PFH-PEG@PLGA nanoparticles can perform as a marvelous synergistic agent for enhanced FUS/chemotherapy, promote real-time contrast enhanced US imaging and improve the therapeutic efficacy and prognosis of TNBC.
研究领域:
肿瘤学
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纳米技术
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医学影像
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癌症治疗
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生物医学工程
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DOI
PubMed
高影响因子
Journal of Pharmaceutical Investigation
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2024
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IF 5.3
Zhou Limei,Shang Yunxia,Wang Yaru,Wei Xiaohui
Purpose Ulcerative colitis (UC) is a chronic and non-specific inflammatory bowel disease that poses a serious threat to individuals' health and lives. Notoginsenoside R1 (R1) alleviates various symptoms caused by UC effectively. However, the application of R1 is somewhat restricted due to its low bioavailability and nontargeted delivery in vivo. Consequently, it is imperative to develop novel strategies to overcome the aforementioned limitations and enhance the efficacy of this drug. To enhance R1's efficacy and targeting ability, polyethylene glycol poly (lactic-co-glycolic acid) nanoparticles loaded with R1 (R1@PEG–PLGA NPs) modified by transferrin (Tf) were prepared in this study and named R1@Tf–PEG–PLGA NPs. Methods R1@PEG–PLGA NPs and R1@Tf–PEG–PLGA NPs were prepared through nanoprecipitation, and the characterization methods were as follows: First, the surface morphology of the NPs was studied through transmission electron microscopy. Second, particle size, polydispersity index (PDI), and zeta potential were measured with a Malvern particle size analyzer, and the Tf grafting rate on the surface of the NPs was determined by using a bicinchoninic acid protein quantification kit. Third, high-performance liquid chromatography was used in determining the drug load (DL), entrapment efficiency (EE), and in vitro release of the prepared preparation. In addition, the fluorescence intensities of fluorescent-labeled NPs absorbed and ingested in Caco-2 cells were observed through in vitro experiments using fluorescence microscopy; the effects of incubation time, incubation temperature, and endocytosis inhibitors on the uptake of nanoparticles were compared; and the uptake-transport mechanism was explored. Finally, in vivo experiments were performed using the oxazolone (OXZ)-induced UC model in Sprague–Dawley (SD) rats to assess the pharmacodynamic effects and tissue distribution of the prepared NPs. Results The experimentally prepared R1@Tf–PEG–PLGA NPs were round particles with particle size and PDI of 153.50 ± 2.01 and 0.11 ± 0.01, respectively. In addition, the DL of R1@Tf-PEG-PLGA NPs was 24.26% ± 0.18%, and the EE was 50.32% ± 0.86%. Furthermore, R1@Tf–PEG–PLGA NPs had a slower cumulative release rate in vitro than R1 and R1@PEG–PLGA NPs. Fluorescence results showed that under the same conditions, Caco-2 cells took up more Tf-PEG–PLGA NPs than they took up PEG–PLGA NPs. Studies on the cellular uptake mechanism of absorption and uptake determined that the PEG–PLGA NPs entered the cells mainly through fovea-mediated endocytosis, whereas the Tf–PEG–PLGA NPs entered the cells mainly through fovea-mediated and lattice protein-mediated endocytosis. In vivo intestinal tissue distribution results in OXZ-induced SD rats showed that R1@Tf–PEG–PLGA NPs were more enriched in the colon than R1 and R1@PEG–PLGA NPs, and pharmacodynamic evaluation showed that R1@Tf–PEG–PLGA NPs exhibited more pronounced effects in ameliorating colonic injury. Conclusion R1@Tf–PEG–PLGA NPs showed significant colonic targeting and anti-UC effect, showing promising applications.
研究领域:
药学
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纳米技术
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炎症性肠病
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药物递送系统
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产品关联
DOI
高影响因子
Bioactive Materials
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2022
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IF 16.874
Jingxin Hou,Jun Zhou,Meiqi Chang,Guangcheng Bao,Jie Xu,Man Ye,Yixin Zhong,Shuling Liu,Junrui Wang,Wei Zhang,Haitao Ran,Zhigang Wang,Yu Chen,Dajing Guo
Due to the high risk of tearing and rupture, vulnerable atherosclerotic plaques would induce serious cardiovascular and cerebrovascular diseases. Despite the available clinical methods can evaluate the vulnerability of plaques and specifically treat vulnerable plaques before a cardiovascular event, but the efficiency is still low and undesirable. Herein, we rationally design and engineer the low-intensity focused ultrasound (LIFU)-responsive [email protected] nanomedicine for the highly efficient treatment of vulnerable plaques by facilely loading phase transition agent perfluorohexane (PFH) into biocompatible PLGA-PEG-PLGA nanoparticles (PPP NPs) and then attaching dextran sulphate (DS) onto the surface of PPP NPs for targeting delivery. DS, as a typical macrophages-targeted molecule, can achieve the precise vaporization of NPs and subsequently controllable apoptosis of RAW 264.7 macrophages as induced by acoustic droplet vaporization (ADV) effect. In addition, the introduction of DiR and Fe 3 O 4 endows nanomedicine with near-infrared fluorescence (NIRF) and magnetic resonance (MR) imaging capabilities. The engineered [email protected] nanomedicine that uses macrophages as therapeutic targets achieve the conspicuous therapeutic effect of shrinking vulnerable plaques based on in vivo and in vitro evaluation outcomes. A reduction of 49.4% of vascular stenosis degree in gross pathology specimens were achieved throughout the treatment period. This specific, efficient and biosafe treatment modality potentiates the biomedical application in patients with cardiovascular and cerebrovascular diseases based on the relief of the plaque rupture concerns.
研究领域:
纳米技术
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生物医学工程
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心脏病学
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药理学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）