EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
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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
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产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
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2013
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IF 3.463
Yan Xiao,Huafang Zhang,Zhaoguo Zhang,Mina Yan,Ming Lei,Ke Zeng,Chunshun Zhao
For the purposes of obtaining a hepatocyte-selective drug delivery system, a novel tetravalent galactosylated diethylenetriaminepentaacetic acid-distearoyl phosphatidylethanolamine (4Gal-DTPA-DSPE) was synthesized. The chemical structure of 4Gal-DTPA-DSPE was confirmed by proton nuclear magnetic resonance and mass spectrometry. The four galactose-modified liposomes (4Gal-liposomes) were prepared by thin-film hydration method, then doxorubicin (DOX) was encapsulated into liposomes using an ammonium sulfate gradient loading method. The liposomal formulations with 4Gal-DTPA-DSPE were characterized by laser confocal scanning microscopy and flow cytometry analysis, and the results demonstrated that the 4Gal-liposomes facilitated the intracellular uptake of DOX into HepG2 cells via asialoglycoprotein receptor-mediated endocytosis. Cytotoxicity assay showed that the cell proliferation inhibition effect of 4Gal-liposomes was higher than that of the conventional liposomes without the galactose. Additionally, pharmacokinetic experiments in rats revealed that the 4Gal-liposomes displayed slower clearance from the systemic circulation compared with conventional liposomes. The organ distributions in mice and the study on frozen sections of liver implied that the 4Gal-liposomes enhanced the intracellular uptake of DOX into hepatocytes and prolonged the circulation. Taken together, these results indicate that liposomes containing 4Gal-DTPA-DSPE have great potential as drug delivery carriers for hepatocyte-selective targeting.
研究领域:
药剂学
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分子生物学
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药物代谢动力学
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产品关联
DOI
PubMed
高影响因子
Food Analytical Methods
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2022
·Vol. 15
·期 9
·2479-2486
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IF 3.498
Zhang Shengnan,Li Zhibo,Qi Yanxia,Yu Pei,Zhao Qiancheng
The determination of 2-acetyl-1-pyrroline (2-AP), which is an important flavour compound of crustaceans and has a low odour threshold of 0.05 μg/L in water, is still a challenge due to the instability and trace levels of 2-AP in food samples. In this study, 2-AP was trapped by o-phenylenediamine and subsequently purified by the dispersive solid-phase extraction and dispersive liquid–liquid microextraction (DSPE-DLLME) methods for HPLC–UV analysis. The developed method was simple, fast and sensitive for the determination of 2-AP in shrimp. Under the optimized DSPE-DLLME conditions, the developed method exhibited excellent linearity ( R 2 = 0.996) and a low limit of detection (LOD, 1.77 μg/kg) and limit of quantitation (LOQ, 5.33 μg/kg). The recoveries of 2-AP in shrimp ranged from 86.3 to 101.6%. In addition, the developed method was applied to detect 2-AP levels in baked shrimp (ranging from 5.6 to 12.6 μg/kg), indicating that the formation of 2-AP could be observed in thermally treated shrimp depending on heating temperature and time. In summary, the developed method has potential application for the trace determination of 2-AP in shrimp due to its convenience and high sensitivity.
研究领域:
食品科学
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分析化学
✓ 已验证
DOI
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2017
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IF 3.887
Fuqiang Guo,Jiajia Shang,Hai Zhao,Kangrong Lai,Yang Li,Zhongxiong Fan,Zhenqing Hou,Guanghao Su
As one of nanomedicine delivery systems (NDSs), drug nanocrystals exhibited an excellent anticancer effect. Recently, differences of internalization mechanisms and subcellular localization of both drug nanocrystals and small molecular free drug have drawn much attention. In this paper, paclitaxel (PTX) as a model anticancer drug was directly labeled with 4-chloro-7-nitro-1, 2, 3-benzoxadiazole (NBD-Cl) (a drug-fluorophore conjugate Ma et al. (2016) and Wang et al. (2016) [1,2] (PTX-NBD)). PTX-NBD was synthesized by nucleophilic substitution reaction of PTX with NBD-Cl in high yield and characterized by fluorescence, XRD, ESI–MS, and FT-IR analysis. Subsequently, the cube-shaped PTX-NBD nanocrystals were prepared with an antisolvent method followed by surface functionalization of SPC and MPEG-DSPE. The obtained specific shaped [email protected] NCs had a hydrodynamic particle size of ∼50 nm, excellent colloidal stability, and a high drug-loading content of ∼64%. Moreover, in comparison with free PTX-NBD and the sphere-shaped PTX-NBD nanocrystals with surface functionalization of SPC and MPEG-DSPE ( [email protected] NSs), [email protected] NCs remarkably reduced burst release and improved cellular uptake efficiency and in vitro cancer cell killing ability. In a word, the work highlights the potential of theranostic prodrug nanocrystals based on the drug-fluorophore conjugates for cell imaging and chemotherapy.
研究领域:
药学
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纳米技术
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癌症研究
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产品关联
DOI
PubMed
高影响因子
FOOD CHEMISTRY
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2022
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IF 9.231
Qin Huang,Hua Zhou,Xianglun Wu,Chenli Song,Jiangang Zheng,Meikang Lei,Pengqian Mu,Pinggu Wu
Liquid chromatography coupled with quadrupole linear ion trap tandem mass spectrometry (LC-QLIT-MS/MS) technology operated in electrospray ionization (ESI) was developed for tracing anesthetic (AETs) and sedatives (SDTs) in fish. Sampling procedure was achieved by using acetonitrile extraction followed by dispersive solid phase extraction (DSPE) clean-up. Under the optimized laboratory conditions, reliable qualitative confirmation was obtained through the multiple reaction monitoring-information dependent acquisition-enhanced product ion (MRM-IDA- EPI ) mode. Results indicated a favorable linear in the concentration range of 1–100 μg∙kg −1 (0.1–10 μg∙kg −1 for MS-222), with regression coefficient not less than 0.9997. The detection limit ranges from 0.03 to 0.4 μg∙kg −1 (S/N = 3). The validated method was applied to determine AETs and SDTs in fish with satidfied recoveries of 86.3 %–111.7 % and the relative standard deviations (RSD) of 1.9 %–8.9 % (n = 6). Practical samples analysis indicated that the proposed method is simple, rapid, sensitive and accurate for identification of AETs and SDTs.
研究领域:
分析化学
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食品安全
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF MATERIALS SCIENCE & TECHNOLOGY
·
2024
·
IF 11.2
Jiejun Ren,Longyun Liu,Fan Liu,Huiping Liu,Xiaopeng Zhou,Gen Li,Liangjun Chen,Guoping Yan,Yuhua Wang
Lead halide perovskite (LHP) nanocrystals (NCs) suffer from poor stability against environmental factors (heat, moisture, oxygen, etc.), which seriously hinders their practical application. Constructing a core-shell structure could be an effective approach to improve the stability and optical properties of the LHP NCs. Herein, a novel strategy of water-triggered phase transformation and phospholipid (DSPE) micelle encapsulation is proposed, generating highly luminescent water-dispersed CsPbBr 3 @CsPb 2 Br 5 @DSPE core-shell-shell nanocrystals. The epitaxial growth of the CsPb 2 Br 5 shell is induced by the in-situ reconstruction of the CsPbBr 3 surface by water erosion, and the lattice mismatch with the CsPbBr 3 core is small (3.8%). The further amphipathic phospholipid encapsulation guarantees their excellent water dispersity and stability. Revealed by the femtosecond transient absorption spectroscopy, the dense CsPb 2 Br 5 @DSPE shell effectively passivates the surface of the CsPbBr 3 core, thus improving its stability and luminescence performance. The resulting CsPbBr 3 @CsPb 2 Br 5 @DSPE nanoparticles exhibit excellent performance as fluorescent probes for bioimaging, aqueous inks for high-resolution pattering, and light conversion layers for LEDs, demonstrating their promising potential in multiple applications.
研究领域:
材料科学
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生物医学工程
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光学工程
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产品关联
DOI
高影响因子
PHARMACEUTICAL RESEARCH
·
2018
·Vol. 35
·期 1
·1-15
·
IF 3.335
Jin Ya,Wu Zimei,Li Caibin,Zhou Weisai,Shaw John P.,Baguley Bruce C.,Liu Jianping,Zhang Wenli
Purpose To enhance therapeutic efficacy and prevent phlebitis caused by Asulacrine (ASL) precipitation post intravenous injection, ASL-loaded hybrid micelles with size below 40 nm were developed to improve drug retention and tumor penetration. Methods ASL-micelles were prepared using different weight ratios of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-polyethyleneglycol-2000 (DSPE-PEG 2000 ) and D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) polymers. Stability of micelles was optimized in terms of critical micelle concentration (CMC) and drug release properties. The encapsulation efficiency (EE) and drug loading were determined using an established dialysis-mathematic fitting method. Multicellular spheroids (MCTS) penetration and cytotoxicity were investigated on MCF-7 cell line. Pharmacokinetics of ASL-micelles was evaluated in rats with ASL-solution as control. Results The ASL-micelles prepared with DSPE-PEG 2000 and TPGS (1:1, w /w) exhibited small size (~18.5 nm), higher EE (~94.12%), better sustained in vitro drug release with lower CMC which may be ascribed to the interaction between drug and carriers. Compared to free ASL, ASL-micelles showed better MCTS penetration capacity and more potent cytotoxicity. Pharmacokinetic studies demonstrated that the half-life and AUC values of ASL-micelles were approximately 1.37-fold and 3.49-fold greater than that of free ASL. Conclusions The optimized DSPE-PEG 2000 /TPGS micelles could serve as a promising vehicle to improve drug retention and penetration in tumor.
研究领域:
药剂学
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肿瘤学
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药物递送系统
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生物药剂学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY
·
2021
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IF 3.232
Yang Gao,Ya Sun,Guangli Liao,Hailong Zhang,Qingzhi Long
Objective This study aims to investigate the potential of DSPE-PEG polymers (DSPE-PEG-OH and DSPE-PEG-SH) on improving absorption of poorly absorbable macromolecules via intrapulmonary administration and underlying mechanism.Methods In situ pulmonary absorption experiments were performed to investigate the absorption of model compounds after intrapulmonary administration to rats. The local membrane damage induced by these DSPE-PEG polymers were evaluated based on morphological observation of lung tissues and measurement of biological toxic markers in bronchoalveolar lavage fluid (BALF) postintrapulmonary delivery of DSPE-PEG polymers to rats. The underlying enhancement mechanism of these polymers was explored by investigating their effects on the pulmonary membrane fluidity and gene expression of tight junction associated proteins with fluorescence polarization and western blotting, respectively.Results Intrapulmonary delivery of these DSPE-PEG polymers significantly enhanced absorptions of poorly absorbed model drugs and did not induce serious damage to the pulmonary membranes of rats. Mechanistic studies demonstrated unaffected pulmonary membrane fluidity and up-regulated expression levels of tight junction-associated proteins by DSPE-PEG polymers, thus indicating that paracellular pathways might be included in the underlying mechanisms by which DSPE-PEG polymers exerted their enhancing actions on drug absorption.Conclusions These findings suggested that these DSPE-PEG polymers are potential for promoting absorptions of poorly absorbable macromolecules with no evidence of damage to the local pulmonary membranes of rats.Novelty statementIn this study, DSPE-PEG-OH and DSPE-PEG-SH polymers, two DSPE-PEG2000 conjugates with different terminal groups demonstrated significant promoting effects on the absorption of poorly absorbed macromolecular drugs after intrapulmonary delivery to rats, and did not induce serious damage to the pulmonary membranes of rats. These DSPE-PEG polymers could statistically downregulate expression levels of tight junction-associated proteins (ZO-1 and occludin), indicating the underlying mechanism by which these polymers exerted their absorption enhancing actions through pulmonary epithelial paracellular pathways. Thus, this study exhibited prospective potential of these DSPE-PEG polymers in developing into dosage forms with the aim to improve the poor bioavailability of some poorly absorbed macromolecular drugs.
研究领域:
药学
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药理学
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生物药剂学
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产品关联
DOI
PubMed
高影响因子
RSC Advances
·
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
✓ 已验证
产品关联
DOI
高影响因子
Biomaterials Science
·
2023
·Vol. 11
·期 12
·4335-4345
·
IF 6.6
Penghui Wang,Yuling Wang,Xuelin Xia,Wei Huang,Deyue Yan
Multidrug resistance (MDR) is a major cause of chemotherapy failure in cancer treatment. P-glycoprotein (P-gp) inhibitors are helpful for chemotherapy drugs to overcome tumor MDR effectively. With the traditional physical mixing of chemotherapy drugs and inhibitors, it is difficult to achieve satisfactory results due to the different pharmacokinetics and physicochemical properties between the two of them. Herein, we prepared a novel drug-inhibitor conjugate prodrug (PTX-ss-Zos) from a cytotoxin (PTX) and a third-generation P-gp inhibitor (Zos) linked with a redox-responsive disulfide. Then, PTX-ss-Zos was encapsulated in DSPE-PEG2k micelles to form stable and uniform nanoparticles (PTX-ss-Zos@DSPE-PEG2k NPs). PTX-ss-Zos@DSPE-PEG2k NPs could be cleaved by the high-concentration GSH in cancer cells and release PTX and Zos simultaneously to inhibit MDR tumor growth synergistically without apparent systemic toxicity. The in vivo evaluation experiments exhibited that the tumor inhibition rates (TIR) of PTX-ss-Zos@DSPE-PEG2k NPs were high up to 66.5% for HeLa/PTX tumor-bearing mice. This smart nanoplatform would bring new hope for cancer treatment in clinical trials.
研究领域:
药学
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癌症研究
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纳米技术
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药物递送系统
✓ 已验证
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2024
·
IF 6.6
Huiyun Zhang,Shunru Wei,Yunfei Hu,Yu Zhang,Hao Yao,Gang Qi,Michael Adu-Frimpong,Congyong Sun
Background Bufalin (BFL, an active anti-tumor compound derived from toad venom) is limited in its application due to high toxicity and rapid metabolism of the cardiotonic steroid. Ester prodrug self-assembly nanoparticles have shown significant improved effects in addressing the above-mentioned issues.Methods An ester bond was formed between linoleic acid and bufalin to synthesize linoleic acid-bufalin prodrug (LeB). The self-assembly nanoparticles (LeB-PSNs) containing different mass ratios of DSPE-PEG2k and prodrug (6:4, 7:3, 8:2, 9:1 and 10:0) were prepared via co-precipitation method and defined as 6:4-PSNs, 7:3-PSNs, 8:2-PSNs, 9:1-PSNs and LeB-PSNs, respectively. Further, the characterization (particle size, zeta potential, surface morphology and stability) of the nanoparticles was carried out. Finally, we evaluated the impact of different ratios of DSPE-PEG2k on the hydrolysis rate, cytotoxicity, cellular uptake, cell migration and proliferation suppression potential of the prodrug nanoparticles.Results The linoleic acid-bufalin prodrug (LeB) was successfully synthesized. Upon the addition of DSPE-PEG2k at different weight ratios, both particle size and polydispersity index (PDI) significantly decreased, while the zeta potential increased remarkably. No significant differences in particle size, PDI and Zeta potential were observed among the 9:1, 8:2 and 7:3 PSNs. Notably, the 8:2 (w/w) DSPE-PEG2k nanoparticles exhibited superior stability, hydrolysis and cellular uptake rates, along with efficient cell cytotoxicity, cell migration and proliferation suppression.Conclusion These findings indicate that DSPE-PEG2k could improve the performance of BFL prodrug nanoparticles, namely enhancing stability and achieving adaptive drug release by modulating the hydrolysis rate of esterase. This study therefore provides more opportunities for the development of BFL application.
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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肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PROCESS BIOCHEMISTRY
·
2023
·
IF 4.4
Xiaoxuan Cai,Miaoen Huang,Xixiang Huang,Huan Liu,Tianji Wang,Li Li,Weiguang Yang,Hui Luo,Yingnian Lu
The organism Sipunculus nudus L is a good resource for marine peptides because of its rich protein. However, the disadvantage of biological peptides is their short metabolic half-life, therefore, structural modification of peptides is necessary. In this research, the enzymatic hydrolysis of Sipunculus nudus L was performed using trypsin and then peptides were isolated and purified from the hydrolysates, four novel tripeptides were identified by LC-MS-MS as Ser-Arg-Pro (SRP, m/z = 358.39), Pro-Arg-Pro (PRP, m/z = 368.43), Arg-Pro-Ala (RPA, m/z = 342.39), and Lue-Pro-Lys (LPK, m/z = 356.46), their ACE inhibitory activity was investigated with IC 50 value as following 0.046, 0.42, 0.97, and 6.54 mM, respectively. Because of its highest ACE inhibitory activity, SRP was further selected to modify the chemical structure for a sustained release agent DSPE-PEG-SRP. Compared with 7 h of free SRP, the release of DSPE-PEG-SRP in vitro was approximately 120 h. The ACE inhibition rate of SRP released from the synthetic product and the raw material SRP was almost the same, molecular docking demonstrated that ACE inhibitory activity was attributed to the formation of hydrogen bonds between SRP and ACE active sites . In conclusion, DSPE-PEG-SRP, a novel sustained release agent, has great potential and is expected to be further applied to treat hypertension.
研究领域:
海洋生物学
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药学
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生物化学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）