MOLECULAR PHARMACEUTICS
·
2018
·
IF 4.556
Feiyang Jin,Di Liu,Hui Yu,Jing Qi,Yuchan You,Xiaoling Xu,Xuqi Kang,Xiaojuan Wang,Kongjun Lu,Xiaoying Ying,Jian You,Yongzhong Du,Jiansong Ji
Acute lung injury (ALI) is a serious illness without resultful therapeutic methods commonly. Recent studies indicate the importance of oxidative stress in the occurrence and development of ALI, and mitochondria targeted antioxidant has become a difficult and hot topic in the research of ALI. Therefore, a sialic acid (SA)-modified lung-targeted microsphere (MS) for ALI therapy are developed, with triphenylphosphonium cation (TPP)-modified curcumin (Cur-TPP) loaded, which could specifically target the mitochondria, increasing the effect of antioxidant. The results manifest that with the increase of microsphere, lung distribution of microsphere is also increased in murine mice, and after SA modification, the microsphere exhibits the ideal lung-targeted characteristic in ALI model mice, due to SA efficiently targeting to E-selectin expressed on inflammatory tissues. Further investigations indicate that SA/Cur-TPP/MS has better antioxidative capacity, decreases intracellular ROS generation, and increases mitochondrial membrane potential, contributing to a lower apoptosis rate in human umbilical vein endothelial cells (HUVECs) compared to H2O2 group. In vivo efficacy of SA/Cur-TPP/MS demonstrates that the inflammation has been alleviated markedly and the oxidative stress is ameliorated efficiently. Significant histological improvements by SA/Cur-TPP/MS are further proved via HE stains. In conclusion, SA/Cur-TPP/MS might act as a promising drug formulation for ALI therapy.
研究领域:
药学
·
生物医学工程
·
药理学
·
治疗学
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药物递送系统
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肺疾病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN POLYMER JOURNAL
·
2023
·
IF 6
Junwei Xu,Yi Cui,Meili Liu,Zitong An,Kun Li,Xuenan Gu,Ping Li,Yubo Fan
The incidence of cancer and other diseases continues to increase, posing a serious threat to human health. Drug delivery systems using bionic red blood cell (RBC)-like microparticles (MPs) as drug carriers have been extensively studied, as they are considered ideal carriers due to the unique shape. However, most methods of preparing multifunctional RBC-like MPs are complicated, and the cell affinity and therapeutic effect of MPs prepared using simple electrospray are unsatisfactory. In this context, hydrophilicity-enhanced and magnetic-luminescent bifunctional RBCs-like Janus MPs [Fe 3 O 4 @poly(lactic-co-glycolic acid) (PLGA)-poly(ethylene glycol) (PEG)-PLGA/PLGA]//[NaYF 4 :Eu 3+ @PLGA-PEG-PLGA/PLGA] were successfully prepared by one-step double-needle electrospray method. The physical and chemical properties, such as morphology, particle size, structure, and thermal stability of the MPs, were studied. The addition of block polymer PLGA-PEG-PLGA was found to enhance the hydrophilicity of the MPs, promote cell spreading and adhesion proteins (focal adhesion kinase and Paxillin) mRNA expressions of human umbilical vein endothelial cells, significantly improving the cell affinity. The results also demonstrated that RBC-like MPs exhibited excellent magnetic and enhanced luminescent properties, making them a promising candidate for various biomedical applications, including drug delivery systems, magnetic targeting, bio-imaging, and fluorescent tracing.
研究领域:
生物医学工程
·
材料科学
·
药学
·
细胞生物学
✓ 已验证
DOI
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2020
·
IF 4.845
Xin Jin,Qiang Fu,Zehui Gu,Zhenhai Zhang,Huixia Lv
The stroma in solid tumors severely impedes drug delivery via systemic administration to cancer cells, especially when using nano-drug delivery systems. Therefore, we developed thermosensitive and in situ-formed hydrogels based on PLGA–PEG–PLGA, which delivered corilagin and low-molecular-weight chitosan (LC) directly to tumor cells via intratumor injection and promoted drug infiltration by modulating the tumor microenvironment . The hydrogels showed the desired thermosensitive properties and enabled corilagin to elicit its highest antitumor effect. Moreover, in 4T1 tumor-bearing mice, upon combination with the hydrogels, Abraxane® exhibited a better antitumor efficacy and increased paclitaxel accumulation in the tumor tissue by degradation of the tumor matrix caused by corilagin and the uptake-promoting effect of low-molecular-weight chitosan. These results suggest that the strategy of intratumor injection of hydrogels combined with systemic administration of drugs, especially nanotherapeutics, holds promise for enhanced treatment of malignant solid tumors.
研究领域:
药学
·
癌症研究
·
药物递送系统
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY
·
2020
·
IF 2.365
Xinrui Li,Jing Su,Zul Kamal,Pengcheng Guo,Xinyi Wu,Lina Lu,Hongbing Wu,Mingfeng Qiu
Curcumin (Cur) is a promising drug for neurological diseases. Nevertheless, the application of Cur has been limited due to its difficulty in penetrating blood-brain barrier (BBB). Intranasal drug delivery, a noninvasive alternative delivery of Cur, can effectively help Cur cross BBB and inert into central nervous system directly. Odorranalectin (OL) which is the smallest lectin can prolong the residence time of Cur in the nasal mucosa and promote cellular uptake. In this work, a nasal delivery system incorporating OL modified Cur-loaded nanoparticles (Cur–OL–NPs) was developed and expected to bypass BBB and promote the absorption of Cur. We conjugated OL to polyethylene glycol-poly (lactic-co-glycolic acid) (PEG–PLGA), and combined polyethylene glycol-poly (γ-benzyl-L-glutamate) (PEG–PBLG) and OL–PEG–PLGA to prepare nanoparticles to improve the stability, bioavailability and targeting of Cur. Compared with unmodified NPs, increased efficiency of Cur–OL–NPs cellular uptake by Calu-3 cells had been obtained with no severe toxicity. Furthermore, in vivo pharmacokinetic studies also showed that Cur–OL–NPs had higher relative bioavailability. Thus, it is concluded that the results indicated that OL–NPs as carriers of Cur had a promising future in nasal drug delivery system.
研究领域:
药剂学
·
神经科学
·
生物材料学
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产品关联
DOI
PubMed
高影响因子
LAB ON A CHIP
·
2024
·
IF 6.1
Wenwen Chen,Hao Li,Xinyue Zhang,Yutao Sang,Zhihong Nie
Monodisperse biodegradable polymer microspheres show broad applications in drug delivery and other fields. In this study, we developed an effective method that combines microfluidics with interfacial instability to prepare monodispersed poly(lactic-co-glycolic acid)-b-polyethylene glycol (PLGA-PEG)/poly(lactic-co-glycolic acid) (PLGA) microspheres with tailored surface morphology. By adjusting the mass ratio of PLGA-PEG to PLGA, the concentration of stabilizers and the type of PLGA, we generated microspheres with various unique folded morphologies, such as “fishtail-like”, “lace-like” and “sponge-like” porous structures. Additionally, we demonstrated that risperidone-loaded PLGA-PEG/PLGA microspheres with these folded morphologies significantly enhanced drug release, particularly in the initial stage, by exhibiting a logarithmic release profile. This feature could potentially address the issue of delayed release commonly observed in sustained-release formulations. This study presents a straightforward yet effective approach to construct precisely engineered microspheres offering enhanced control over drug release dynamics.
研究领域:
药剂学
·
材料科学
·
药物递送系统
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2020
·
IF 2.734
Bo Yu,Ying Pu,Jun Liu,Jie Liao,Ke Chen,Jiani Zhang,Wen Zhong,Yalan Hu,Xue-Qiang Wang,Bo Liu,Huixia Liu,Weihong Tan
Targeted delivery of antiobesity drugs to adipocytes presents a novel strategy for obesity treatment. The 11 beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1) in adipose tissue is an attractive therapeutic target of obesity. Emodin (EMO) has been proven to be a potent and selective inhibitor of 11β-HSD1, but it frequently exerts low bioavailability owing to its poor water solubility and lack of tissue specificity. In this work, we conjugated a nanoscale drug delivery polymer with Adipo8 (Ap), a DNA aptamer with high affinity to mature white adipocytes, as a targeting modality that enabled selective delivery of emodin to adipocytes. Emodin-loaded PEG-PLGA nanoparticles (EMO-NPs) were formulated by a modified oil-in-water (O/W) emulsion solvent evaporation method, and Ap was covalently bound to the NP surface via the EDC/NHS method. The NPs were structurally investigated by TEM imaging, DLS and UV-VIS spectroscopy. The resulting aptamer-conjugated, emodin-loaded nanoparticles (Ap-EMO-NPs) had a spherical shape and an average particle size of 146.7 ± 27.85 nm with a drug loading of around 6.8% and a sustained-release property. Confocal microscopy and flow cytometry demonstrated a significant increase in the internalization of Ap-EMO-NP in differentiated 3T3-L1 cells compared to EMO-NP functionalized with nonspecific aptamer. As confirmed by Oil Red O coloring, the Ap-EMO-NPs reduced lipid stacking in 3T3-L1 adipocytes in a sustained-release and dose-dependent manner. The results indicated that Adipo8-functionalized PEG-PLGA NPs could be a potential targeted therapeutic delivery vehicle for obesity treatment.
研究领域:
药理学
·
生物医学工程
✓ 已验证
DOI
高影响因子
Frontiers in Pharmacology
·
2023
·
IF 5.6
Huang Yaxian,Wu Jinyan,Zhan Chi,Liu Rong,Zhou Zhaocai,Huang Xin,Tian Yaguang,Lin Zhengmei,Song Zhi
The enhanced osteoclastogenesis contributes to alveolar bone resorption in periodontitis, which increases the risk of tooth loss. To reduce bone destruction, the inhibition of osteoclast development is proposed as a feasible treatment. CD40L-CD40-TRAF6 signal transduction plays a crucial role in inflammation, but how it regulates osteoclast activity in periodontitis has not been elucidated. In this study, we showed the potential role of CD40L-CD40-TRAF6 signaling in periodontitis. CD40L obviously promoted osteoclast formation and bone resorption capacity in vitro. Mechanistically, we found that osteoclastogenesis was enhanced by the overexpression of NFATc1 and NF-κB activation. Importantly, osteoclast activity was effectively suppressed by TRAF-STOP, a small molecular inhibitor of TRAF6. Furthermore, local injection of TRAF-STOP-loaded injectable PLGA-PEG-PLGA hydrogel could alleviate ligation-induced periodontitis in vivo. Taken together, TRAF-STOP shows promising clinical efficacy in periodontitis through alleviating osteoclastogenesis.
研究领域:
牙科学
·
免疫学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY
·
2020
·
IF 2.365
Xuwang Pan,Shourong Liu,Liping Ju,Jianjun Xi,Ruoyu He,Yanmei Zhao,Rangxiao Zhuang,Jinsong Huang
Objective The objective of this study was to prepare the liver targeting drug delivery system (TDDS) of artesunate (ART)-loaded polyethylene glycol (PEG)-poly(d,l-lactic-co-glycolic) acid (PLGA) nanoparticles (NPs) modified by glycyrrhetinic acid (GA), and evaluate its in vitro cytotoxicity.Significance The GA-PEG-PLGA-ART NPs enhanced the in vitro cytotoxicity on HCC cell lines. The development of GA-PEG-PLGA NPs will greatly push the clinical applications of ART as a novel anticancer drug.Methods The NPs were prepared using solvent evaporation method, and the formulation was optimized through an orthogonal design. In addition, physical properties were determined, including particle size, polydispersity index (PDI), zeta potential (ZP), morphology, drug loading capacity (LC) and encapsulation efficiency (EE), and in vitro drug release. Moreover, the in vitro cytotoxicity of NPs with three human cancer cell lines viz. HepG2, Hep3B, and SMCC-7721 was conducted using the SRB assay. Additionally, lyophilization was conducted to improve the long-term physical stability.Results The GA-PEG-PLGA-ART NPs have spherical shape, small particle size (around 88 nm) with a narrow size distribution (PDI < 0.3), high drug LC (up to 59.3 ± 1.65%), and high EE (up to 73.13 ± 5.17%). In vitro drug release behavior showed that drugs were released from NPs in a sustained and controlled release pattern. Cytotoxicity study indicated the NPs achieved lower cancer cell survival fraction. The GA-PEG-PLGA NPs freeze-dried with 3% (w/v) of mannitol showed better effect on long-term physical stability.Conclusion The GA-PEG-PLGA-ART NPs appear as a potential liver targeted intracellular delivery platform for ART.
研究领域:
药剂学
·
肿瘤学
·
纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2023
·
IF 8
Dongyu Duan,Aiping Wang,Ling Ni,Liping Zhang,Xiuju Yan,Ying Jiang,Hongjie Mu,Zimei Wu,Kaoxiang Sun,Youxin Li
Introduction Nanoparticles (NPs) modified with bio-ligands represent a promising strategy for active targeted drug delivery to tumour. However, many targeted ligands, such as trastuzumab (TMAB), have high molecular weight, limiting their application for targeting. In this study, we prepared Fab’ (antigen-binding fragments cut from TMAB)-modified NPs (Fab′-NPs) with curcumin (Cur) as a model drug for more effective targeting of human epidermal growth factor receptor 2 (HER2/ErbB2/Neu), which is overexpressed on breast cancer cells.Material and methods The release kinetics was conducted by dialysis bags. The ability to kill HER2-overexpressing BT-474 cells of Fab′-Cur-NPs compared with TMAB-Cur-NPs was conducted by cytotoxicity experiments. Qualitative and quantitative cell uptake studies using coumarin-6 (fluorescent probe)-loaded NPs were performed by fluorescence microscopy and flow cytometry. Pharmacokinetics and biodistribution experiments in vivo were assessed by liquid chromatography–tandem mass spectrometry (LC-MS/MS).Results The release kinetics showed that both Fab′-Cur-NPs and TMAB-Cur-NPs provided continuous, slow release of curcumin for 72 h, with no significant difference. In vitro cytotoxicity experiments showed that Fab′-Cur-NPs manifested prominent ability to kill HER2-overexpressing BT-474 cells compared with TMAB-Cur-NPs. Qualitative and quantitative cell uptake studies indicated that the accumulation of Fab′-NPs was greater than that of TMAB-NPs in BT-474 (HER2+) cells; However, there was no significant difference in MDA-MB-231 (HER2−) cells. Pharmacokinetics and biodistribution experiments in vivo demonstrated that the half-life (t1/2) and area under the blood concentration-time curve (AUC0-t) of Fab′-Cur-NPs increased 5.30-fold and 1.76-fold relative to those of TMAB-Cur-NPs, respectively. Furthermore, the tumor accumulation of Fab′-Cur-NPs was higher than that of TMAB-Cur-NPs.Conclusion Fab′ fragment has greater capacity than the intact antibody to achieve tumor targeting through NP-based delivery.
研究领域:
药剂学
·
肿瘤学
·
生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING SCIENCE
·
2024
·
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
·
材料科学
·
纳米技术
✓ 已验证
产品关联
DOI
高影响因子
CHINESE JOURNAL OF POLYMER SCIENCE
·
2016
·Vol. 34
·期 6
·730-738
·
IF 1.811
Wen Ji-jie,Lu Hong-guang,Liu De-e,Gao Hui
A series of β -cyclodextrin-conjugated 4-arm poly(ethylene glycol)-poly(lactide- co -glycolide) (4-arm PEG-PLGA) copolymers were synthesized by a ring-opening polymerization of D,L-lactide and glycolide using 4-arm PEG as initiator, and then conjugated with mono(6-ethylenediamine-6-deoxy)- β -cyclodextrin (CDen) or ethylenediamino-bridged bis- β -CD (BCDen). The chemical structures of copolymers were confirmed by 1 H-NMR and FTIR spectroscopy. The β -CD-conjugated PEG-PLGA formed stable reverse micelles due to the formation of β -CD and bovine serum albumin (BSA) inclusion complexation, which could accommodate BSA in the organic solvent with improved encapsulation efficiency. Moreover, we demonstrated a one-step approach to construct macroporous protein-containing films using these reverse micelles. The films with ordered pore arrays were directly prepared from reverse micelles. Interestingly, the protein was totally located in the whole matrix except for the pores.
研究领域:
材料科学
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
AAPS PHARMSCITECH
·
2023
·Vol. 24
·期 8
·1-12
·
IF 3.3
Jiang Wenjing,Gao Xiangjun,Wang Qiuli,Chen Yang,Li Dan,Zhang Xiaoyan,Yang Xinggang
The existing exenatide microspheres have the problem of burst release in the early stage, and minimal release in the middle stage which makes it difficult to achieve effective blood drug concentration (platform period). In this study, the modified exenatide microspheres were constructed to address the aforementioned issues. Poly(D,L-lactic-co-glycolic acid) (PLGA) and triblock copolymer with sol-gel conversion characteristics (PLGA-PEG-PLGA gel) were introduced as carriers to prepare microspheres. The hot gel characteristics and hydrophilicity of PLGA-PEG-PLGA gel were utilized to decline the burst release and shorten the platform period. Simultaneously, zinc acetate and exenatide were combined to generate an insoluble complex to further reduce the burst release. Herein, we prepared three types of exenatide microspheres using the solvent evaporation method and investigated their characterization as well as in vitro and in vivo release. According to the experimental findings, the modified exenatide microspheres, i.e., PLGA-PEG-PLGA gel and PLGA co-loaded zinc-exenatide insoluble complex microspheres (Zn-EXT-Gel-MS), had smooth and rounded surfaces, with a particle size of 24.7 μm, and the encapsulation rate reached 89.43%. And it was released for 40 days in vitro , behaving better than the other two microspheres in terms of release behavior. When this product was administered subcutaneously to rats, it produced a comparatively constant plasma exenatide concentration that lasted for 24 days and superior bioavailability than the exenatide microspheres (EXT-MS). The creation of modified exenatide microspheres may serve as a heuristic method for other long-acting medications. Graphical Abstract Schematic diagram of the synthesis process and release curves of three types of exenatide microspheres in vitro and in vivo
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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）