EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
·
2018
·
IF 3.466
Wenli Zhang,Zhiyu Wang,Chenchen Wu,Ya Jin,Xinyue Liu,Zimei Wu,Jianping Liu
In cholesterol/DSPE-PEG 2000 /DPPC systems, nano-disks could evolve between liposomes and spherical micelles in a certain range of PEG-lipids. How cholesterol or drug influences this evolution and what about the properties of discoidal micelles as drug carrier are still not clear. Aiming at this, nanocarriers with different contents of cholesterol and DSPE-PEG 2000 were prepared by thin-film-hydration method. Firstly, the bilayer fluidity of nanocarriers was investigated and proved to decrease with the increase of cholesterol, and the cooperative degree between phospholipids was also related to cholesterol content in an order of 30 > 40 > 15 > 0 mol%. Then three different levels of cholesterol were chosen to study its effect on DSPE-PEG 2000 limit used to form discoidal micelles. For transition from liposomes to disks, the limit of DSPE-PEG 2000 employed is above 0.5 mol% at 0 mol% cholesterol, above 15 mol% at 30 mol% cholesterol and above 5 mol% at 40 mol% cholesterol observed from TEM images, indicating that nanocarriers with 30 mol% cholesterol formed discoidal micelles most difficultly due to the strongest interaction between phospholipids. However, membrane fluidity seems to have little responsibility for the different morphologies. And imatinib (IM) could promote the formation of discoidal micelles, resulting from the interaction between IM and polar headgroups of phospholipid demonstrated by DSC . The relative reduction of entrapment efficiency for three agents with different dissolving properties showed that lipophilic drugs were the most suitable drug that could be loaded into discoidal micelles. In addition, the discoidal micelle formulations tested could readily change to other morphologies after 80 days' storage. In conclusion, both the cholesterol content and IM could affect the formation of discoidal micelles by probably influencing the interaction between phospholipids, also the discoidal structure was not stable enough and only suitable for lipophilic drug loading. We hope this study could help to design the formula and choose the proper drugs that may retain the discoidal morphology.
研究领域:
药剂学
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生物物理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2020
·Vol. 8
·期 9
·1841-1851
·
IF 5.344
Qin Wang,Liming He,Donghao Fan,Wenlang Liang,Jiyu Fang
Rheumatoid arthritis (RA) is an autoimmune disease that causes chronic inflammation of the joints of the body. Although liposomes are a promising drug delivery vehicle, there is still a challenge of using conventional liposomes for the treatment of RA due to their short circulation time and physicochemical instability in blood vessels. Here, we report the formation of polymerized stealth liposomes composed of 1,2-bis(10,12-tricosadiynoyl)-sn-glycero-3-phosphocholine (DC8,9PC) and 1,2-distearoyl-sn-glycero-3-phospho-ethanolamine-poly(ethyleneglycol) (DSPE-PEG2000) with a thin-film hydration method, in which DC8,9PC molecules are cross-linked in the bilayer of the liposomes by UV irradiation and the PEG chains present at the surface of the liposomes provide a stealth layer. We demonstrate that the polymerized stealth liposomes are stable and show long circulation time in blood vessels. They can be internalized by cells without significant toxicity. After being injected into arthritic rats, the polymerized stealth liposomes with loaded dexamethasone (Dex) show long blood circulation time and accumulate preferentially in inflamed joints, consequently suppressing the level of proinflammatory cytokines (TNF-α and IL-1β) in joint tissues, reducing the swelling of inflamed joints and alleviating the progression of RA. We believe that polymerized stealth liposomes can be used as a promising drug delivery vehicle for various therapeutic applications.
研究领域:
药理学
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药物递送系统
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风湿病学
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纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Science
·
2017
·Vol. 4
·期 4
·1600166
·
IF 9.034
Tingting Li,Dongliang Yang,Liuqing Zhai,Suiliang Wang,Baomin Zhao,Nina Fu,Lianhui Wang,Youtian Tao,Wei Huang
The fluorophores with long-lived fluorescent emission are highly desirable for time-resolved fluorescence imaging (TRFI) in monitoring target fluorescence. By embedding the aggregates of a thermally activated delayed fluorescence (TADF) dye, 2,3,5,6-tetracarbazole-4-cyano-pyridine (CPy), in distearoyl-sn-glycero-3-phosphoethanolamine-poly(ethylene glycol) (DSPE-PEG2000) matrix, CPy-based organic dots (CPy-Odots) with a long fluorescence lifetime of 9.3 μs (in water at ambient condition) and high brightness (with an absolute fluorescence quantum efficiency of 38.3%) are fabricated. CPy-Odots are employed in time-resolved and confocal fluorescence imaging in living Hela cells and in vivo. The green emission from the CPy-Odots is readily differentiated from the cellular autofluorescence background because of their stronger emission intensities and longer lifetimes. Unlike other widely studied DSPE-PEG2000 encapsulated Odots which are always distributed in cytoplasm, CPy-Odots are located mainly in plasma membrane. In addition, the application of CPy-Odots as a bright microangiography agent for TRFI in zebrafish is also demonstrated. Much broader application of CPy-Odots is also prospected after further surface functionalization. Given its simplicity, high fluorescence intensity, and wide availability of TADF materials, the method can be extended to develop more excellent TADF Odots for accomplishing the challenges in future bioimaging applications.
研究领域:
生物医学工程
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生物成像
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材料科学
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2024
·
IF 4.5
Jinmei Lai,Qunying Shi,Yongqi Xie,Yinyin Zhu,Shiyu Liang,Yi Chen,Jiali Yuan,Lihan Liu
Tumoral thermal defense mechanisms considerably attenuate the therapeutic outcomes of mild-temperature photothermal therapy (PTT). Thus, developing a simple, efficient, and universal therapeutic strategy to sensitize mild-temperature PTT is desirable. Herein, we report self-delivery nanomedicines ACy NPs comprising a near-infrared (NIR) photothermal agent (Cypate), mitochondrial oxidative phosphorylation inhibitor (ATO), and distearoylphosphatidylethanolamine-polyethylene glycol 2000 (DSPE–PEG2000), which have a high drug-loading efficiency that can reverse tumoral thermal resistance, thereby increasing mild-temperature PTT efficacy. ACy NPs achieved targeted tumor accumulation and performed NIR fluorescence imaging capability in vivo to guide tumor PTT for optimized therapeutic outcomes. The released ATO reduced intracellular ATP levels to downregulate multiple heat shock proteins (including HSP70 and HSP90) before PTT, which reversed the thermal resistance of tumor cells, contributing to the excellent results of mild-temperature PTT in vitro and in vivo. Therefore, this study provides a simple, biosafe, advanced, and universal heat shock protein-blocking strategy for tumor PTT.
研究领域:
纳米技术
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肿瘤学
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治疗诊断学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2018
·
IF 7.877
Jia Song,Chuchu Lin,Xuan Yang,Yanqi Xie,Ping Hu,Huatian Li,Wenbo Zhu,Haiyan Hu
Mitochondria are ideal anti-tumor target due to mitochondria's central regulation role in cell apoptosis and tumor resistance to apoptosis. There are several challenges for mitochondrial targeting drug delivery, including complex multistep preparations, low drug- loading and systemic toxicity from the carriers. To address these issues, we firstly constructed mitochondria-targeting nanodrugs self-assembled from 9-O-octadecyl substituted berberine derivative (BD) using simple nano-precipitation approach. BD-based nanodrugs were modified by DSPE-PEG2000 (distearylphosphatidylethanolamine- methoxypolyethylene glycol 2000) to increase stability. Negatively charged hyaluronic acid (HA) was further coated to conceal positive charges and achieve tumor targeting. PEG and HA dually modified BD NDs (HA/PEG/BD NDs) were prepared with surface charge of −25.8 mV and high drug loading >70%. The degradation of HA by hyaluronidase (HAase) at tumor tissue allowed the exposure of the positively charged PEG/BD NDs to the cells, which is beneficial for cell uptake and further lysosome escape and mitochondrial targeting. Then, HA/PEG/BD NDs were investigated to induce apoptosis through dissipating mitochondria membrane potential, releasing cytochrome C , increasing the activities of caspase 9/3, activating the pro-apoptotic Bax, suppressing the anti-apoptotic Bcl-2 and upregulating ROS levels. In the A549 xenografted tumor model, HA/PEG/BD NDs exhibited obvious tumor cell mitochondrial targeting and significant anti-tumor efficacy. Overall, comparing to conventional nanoparticles , mitochondrial targeting HA/PEG/BD NDs provide a new strategy for cancer treatment with enhanced drug-loading, relatively simplified preparation processes and reduced carrier toxicities.
研究领域:
药学
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纳米技术
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肿瘤学
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分子生物学
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药物递送系统
✓ 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）