RSC Advances
·
2016
·Vol. 6
·期 80
·76905-76914
·
IF 3.289
Liujie Zhang,Ying Kuang,Jia Liu,Zhilan Liu,Shiwen Huang,Renxi Zhuo
In this paper, a receptor-mediated liposomal drug delivery system (DDS) was developed aiming to deliver cisplatin (cis-diaminedichloroplatinum(II); CDDP) targeting the liver. Acetyl glycyrrhetinic acid (AGA) was chosen as the hepatic targeting ligand and acetyl glycyrrhetinic acid-poly(ethylene glycol)-stearate (AGA-PEG-ST) was synthesized. Anionic 5-cholestene-3-beta-ol-3-hemisuccinate (CHO-HS) was also synthesized. The liposomal CDDPs were prepared by employing these functional moieties with phosphatidylcholine (PC) at various ratios. Meanwhile, methoxypolyethylene glycol-stearate (MPEG-ST) with an analogous structure but without AGA was also prepared as a control. The particle sizes of AGA modified liposomes ranged from 120 nm to 180 nm and the zeta potentials were located between −39.7 mV and −3.18 mV. The liposomes had encapsulation percentages of 51.5–61.7% and a loading capacity of 23.2–26.7% for CDDP. The transmission electron microscopy (TEM) observations showed that the liposomes had spherical morphologies with homogeneous distribution. In vitro cytotoxicity of CDDP-loaded liposomes against HepG2 human liver cancer cells and A549 human lung epithelial carcinoma cells were evaluated by MTT assays. The results demonstrated that the introduction of AGA could enhance the cytotoxicity of liposomal CDDP against HepG2 cells but showed less significant impact on A549 cells. CLSM observation and FCM measurement further confirmed that AGA modified liposomes had a stronger affinity to HepG2 cells than that of liposomes without AGA. The tissue distribution of calcein in mice indicated that AGA modified liposomes resulted in higher accumulation in the liver than that of liposomes without the AGA ligand. These results demonstrated the promise of AGA decorated anionic liposomes for hepatic targeted delivery of cisplatin.
研究领域:
药剂学
·
肿瘤学
·
纳米医学
·
药物递送系统
·
肝病学
✓ 已验证
DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Na Gan,Qinhong Li,Yuanqiao Li,Mohan Li,Yilin Li,Lijuan Chen,Tingting Zeng,Yali Song,Fang Geng,Di Wu
The volatile characteristics of lemongrass essential oil (LO) have seriously hindered its further application, and encapsulation it with multilayer modified liposomes may be an effective strategy to improve this dilemma. This study selected chitosan (CH) and three anionic polymers, pectin (P) / gum arabic (GA) / carrageenan (C), as the first and second coating polymers to modify nano liposomes (NL) by layer-by-layer electrostatic deposition, obtaining three bilayer liposomes, P-CH-NL, GA-CH-NL, and C-CH-NL as high-quality stabilized carriers of LO. The bilayer liposomes showed a dense membrane structure ranging from 110 to 150 nm uniformly, with good antioxidant properties. All bilayer liposomes had good stability during 28-day storage at 4 °C, while C-CH-NL performed relatively better inferred by smaller changes of size, PDI and Zeta potential. The total volatile base nitrogen (TVB-N) values of fresh chicken meat and a total number of bacterial colonies (TBC) experiments showed that GA-CH-NL and C-CH-NL could better retard the increase of volatile salt base nitrogen. All bilayer liposomes could delay the time for the total bacterial count to exceed 6 log CFU/g (from 7 days to 10 / 12 days). Therefore, the bilayer liposomes P-CH-NL, GA-CH-NL, and C-CH-NL may be promising natural preservatives for food products.
研究领域:
食品科学
·
纳米技术
·
生物技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
·
2016
·
IF 3.687
Yinghuan Li,Lei Gao,Xi Tan,Feiyang Li,Ming Zhao,Shiqi Peng
The clathrin-mediated endocytosis is likely a major mechanism of liposomes' internalization. A kinetic approach was used to assess the internalization mechanism of doxorubicin (Dox) loaded cationic liposomes and to establish physiology-based cell membrane traffic mathematic models. Lipid rafts-mediated endocytosis, including dynamin-dependent or -independent endocytosis of noncaveolar structure, was a dominant process. The mathematic models divided Dox loaded liposomes binding lipid rafts ( B ) into saturable binding ( SB ) and nonsaturable binding ( NSB ) followed by energy-driven endocytosis. The intracellular trafficking demonstrated early endosome-late endosome-lysosome or early/late endosome-cytoplasm-nucleus pathways. The three properties of liposome structures, i.e. , cationic lipid, fusogenic lipid, and pegylation, were investigated to compare their contributions to cell membrane and intracellular traffic. The results revealed great contribution of cationic lipid DOTAP and fusogenic lipid DOPE to cell membrane binding and internalization. The valid Dox in the nuclei of HepG2 and A375 cells treated with cationic liposomes containing 40 mol% of DOPE were 1.2-fold and 1.5-fold higher than that in the nuclei of HepG2 and A375 cells treated with liposomes containing 20 mol% of DOPE, respectively, suggesting the dependence of cell type. This tendency was proportional to the increase of cell-associated total liposomal Dox. The mathematic models would be useful to predict intracellular trafficking of liposomal Dox.
研究领域:
药理学
·
细胞生物学
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2024
·
IF 4.5
Xue Zhang,Jiang Chen,Yuan Yin,Shijun Xiao,Rui Zhang,Haiyang Guo,Tong Yang,Tongyu Zhou,Siyan Zhang,Yang Yang,Caili Bi,Xiao-Jun Li
Targeted delivery of chemotherapeutic agents to the cancerous cells is of fundamental importance and the key step of the targeted delivery system design is to choice a specific receptor. Glypican-3 (GPC3) is a known cell membrane-associated oncofetal proteoglycan that is specifically up-regulated in the fast-growing hepatocarcinoma cells but rarely expressed in the normal healthy liver. Therefore, GPC3 may be a perfect targeting receptor for delivery treatment of hepatocellular carcinoma (HCC). In the present study, a GPC3 specific-targeting nanoliposomal drug delivery system was constructed with GPC3 targeting peptide (named as L5 peptide) modification and anticancer drug cantharidin encapsulation, which aims to realize cantharidin targeted treatment of liver cancer. In our study, nanoliposome specifically targeting GPC3 receptor was successfully constructed with particle size of 127.9 nm and a spherical shape. The targeted liposomes were stable under 4 °C or room temperature for almost 15 days. The drug release from L5-modified liposomes was controlled and delayed. Their targeted delivery properties were characterized by relatively more accumulation in the GPC3 highly expressed HepG2 cells than that of GPC3 lowly expressed Huh-7 cells. The competition results also indicated that the liposomes with L5 peptide modification could competitively bind to GPC3 receptor. Moreover, the liposomes showed colocalization with the lysosome after 3 h incubation. The L5-modified liposomal CTD had an augmented cell growth inhibition and tumor inhibition than that of the free CTD on HepG2 cells and GPC3 highly expressed tumor mice. Our study establishes a new strategy for improving HCC treatment and chemotherapeutic agent targeting delivery.
研究领域:
肿瘤学
·
药剂学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2024
·
IF 10.5
Zhi-Chao Sun,Ran Liao,Caihong Xian,Ran Lin,Liying Wang,Yifei Fang,Zhongde Zhang,Yuntao Liu,Jun Wu
Acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) is a high-mortality disease caused by multiple disorders such as COVID-19, influenza, and sepsis. Current therapies mainly rely on the inhalation of nitric oxide or injection of pharmaceutical drugs (e.g., glucocorticoids); however, their toxicity, side effects, or administration routes limit their clinical application. In this study, pachypodol (Pac), a hydrophobic flavonol with anti-inflammatory effects, was extracted from Pogostemon cablin Benth and intercalated in liposomes (Pac@liposome, Pac-lipo) to improve its solubility, biodistribution, and bioavailability, aiming at enhanced ALI/ARDS therapy. Nanosized Pac-lipo was confirmed to have stable physical properties, good biodistribution, and reliable biocompatibility. In vitro tests proved that Pac-lipo has anti-inflammatory property and protective effects on endothelial and epithelial barriers in lipopolysaccharide (LPS)-induced macrophages and endothelial cells, respectively. Further, the roles of Pac-lipo were validated on treating LPS-induced ALI in mice. Pac-lipo showed better effects than did Pac alone on relieving ALI phenotypes: It significantly attenuated lung index, improved pulmonary functions, inhibited cytokine expression such as TNF-α, IL-6, IL-1β, and iNOS in lung tissues, alleviated lung injury shown by HE staining, reduced protein content and total cell number in bronchoalveolar lavage fluid, and repaired lung epithelial and vascular endothelial barriers. As regards the underlying mechanisms, RNA sequencing results showed that the effects of the drugs were associated with numerous immune- and inflammation-related signaling pathways. Molecular docking and western blotting demonstrated that Pac-lipo inhibited the activation of the TLR4-MyD88-NF-κB/MAPK signaling pathway. Taken together, for the first time, our new drug (Pac-lipo) ameliorates ALI via inhibition of TLR4-MyD88-NF-κB/MAPK pathway-mediated inflammation and disruption of lung barrier. These findings may provide a promising strategy for ALI treatment in the clinic.
研究领域:
药理学
·
呼吸病学
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2017
·
IF 3.649
Wenxi Wang,Anna Shao,Shisen Feng,Min Ding,Gan Luo
S-layer proteins (Slps) are crystalline arrays of protein on bacterial cell surface layers. Owning to their capability to reassemble on the surface of lipid layers, Slps have been employed to modify liposomes for various profits. But the interaction information between Slps and positively charged liposomes are destitute, especially the gastrointestinal adhesion of Slps-coating liposomes is rarely reported. In the present work, the Slps extracted from Lactobacillus helveticus were reassembled on the surface of novel positively charged liposomes composed of soybean lecithin , Eudragit ® RL100 and cholesterol. The particle size and remarkable changes of Zeta potential with various Slps/lipid weight ratios were determined by dynamic light scattering and phase analysis light scattering. Significant difference in fluorescence dequenching percentage of liposomes decorated by ODA-FITC confirmed Slps self-reassemble on the surface of liposomes. A higher integrity of vesicular membrane after the addition of Triton X-100 solution demonstrated the stability enhancement of Slps-coating liposomes. Fourier transform infrared (FTIR) spectroscopy illustrated the interaction came from non-covalent bond. The mucoadhesion of Slps-coating liposomes was evaluated by the resident FITC-LP on the gastric and intestinal tract of mice at 7 h and 12 h after intragastrical administration, which proved that the Slps-coating improved the gastrointestinal adhesion significantly.
研究领域:
药剂学
·
生物物理学
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOPARTICLE RESEARCH
·
2021
·Vol. 23
·期 6
·1-16
·
IF 2.253
Wang Qilong,Liu Jing,Liu Jian,Thant Yaminn,Weng Wen,Wei Chunmei,Bao Rui,Adu-Frimpong Michael,Yu Qingtong,Deng Wenwen,Cao Xia,Toreniyazov Elmurat,Ji Hao,Xu Ximing,Yu Jiangnan
Recently, bisdemethoxycurcumin (BDMC), a constituent of turmeric, has been studied widely in view of their various therapeutic effects, namely anti-oxidant, anti-cancer, anti-diabetic, and anti-inflammatory. Since ancient times, turmeric has been extensively used as a naturally occurring traditional Chinese medicine (TCM) and as a crucial home remedy for treatment of many health problems such as inflammation and pain. However, the action of anti-gouty arthritis and analgesic activity of its constituents, especially BDMC, have not been scientifically reported yet. Despite the various bioactivities of BDMC, its utilization in clinics has been restricted owing to poor solubility and bioavailability. This research aimed at enhancing oral bioavailability and pharmacokinetic of BDMC via liposome formulation which was modified with d -α-tocopherol polyethylene glycol 1000 succinate (TPGS or vitamin E TPGS) and was characterized using various parameters both in vitro and in vivo. Also, the analgesic and anti-gouty activities of BDMC-loaded TPGS-modified liposomes were investigated by assessing pain threshold and serum uric acid level in potassium oxonate–induced hyperuricemic rats. As the result, BDMC-loaded TPGS-modified liposomes were formulated successfully with optimal physiochemical properties such as 75.98 ± 5.46 nm (particle size), 0.246 ± 0.011 (polydispersity index), − 38.21 ± 0.29 mV (zeta potential), 96.98 ± 0.17 (encapsulation efficiency (EE%)), and 4.84 ± 0.0089 (drug loading capacity (DL%)). Moreover, the oral bioavailability of liposomized BDMC was approximately 10-fold greater than free BDMC in vivo and in vitro cumulative release rates in pH 1.2 (78%) and pH 7 (68%) respectively. This significantly improved the sustaining drug effect of BDMC compared with free form. In addition, BDMC-TPGS liposome acted as a xanthine oxidase inhibitor to evidently reduce uric acid level in potassium oxonate–induced hyperuricemic rats and remarkably increase pain threshold capacity and reaction time in hot plate test at a dose-dependent manner. Altogether, BDMC-conjugated TPGS liposome could act as favorable nanocarriers against gouty arthritis and intense pain with prospect of overcoming the limitation of BDMC application.
研究领域:
药剂学
·
生物医学
·
中药学
✓ 已验证
DOI
高影响因子
Pharmaceutics
·
2024
·Vol. 16
·期 6
·744
·
IF 4.9
Qianqian Long,Xinmin Zhao,Lili Gao,Mengyuan Liu,Feng Pan,Xihui Gao,Changyou Zhan,Yang Chen,Jialei Wang,Jun Qian
Background:Nanoparticles conjugated with fluorescent probes have versatile applications, serving not only for targeted fluorescent imaging but also for evaluating the in vivo profiles of designed nanoparticles. However, the relationship between fluorophore density and nanoparticle behavior remains unexplored.Methods:The IR783-modified liposomes (IR783-sLip) were prepared through a modified ethanol injection and extrusion method. The cellular uptake efficiency of IR783-sLip was characterized by flow cytometry and fluorescence microscope imaging. The effects of IR783 density on liposomal in vivo behavior were investigated by pharmacokinetic studies, biodistribution studies, and in vivo imaging. The constitution of protein corona was analyzed by the Western blot assay.Results:Dense IR783 modification improved cellular uptake of liposomes in vitro but hindered their blood retention and tumor imaging performance in vivo. We found a correlation between IR783 density and protein corona absorption, particularly IgM, which significantly impacted the liposome performance. Meanwhile, we observed that increasing IR783 density did not consistently improve the effectiveness of tumor imaging.Conclusions:Increasing the density of modified IR783 on liposomes is not always beneficial for tumor near-infrared (NIR) imaging yield. It is not advisable to prematurely evaluate novel nanomaterials through fluorescence dye conjugation without carefully optimizing the density of the modifications.
研究领域:
药剂学
·
生物医学工程
·
分子影像学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2024
·Vol. 29
·期 17
·4001
·
IF 4.2
Sijia Wang,Huifang Xu,Yuanyuan Li,Lingyi Zhang,Shouhong Xu
Stimulus-responsive materials hold significant promise for antitumor applications due to their variable structures and physical properties. In this paper, a series of peptides with a responsive viologen derivative, Pep-CnV (n= 1, 2, 3) were designed and synthesized. The process and mechanism of the interaction were studied and discussed. An ultraviolet–visible (UV) spectrophotometer and fluorescence spectrophotometer were used to study their redox responsiveness. Additionally, their secondary structures were measured by Circular Dichroism (CD) in the presence or absence of the reductant, Na2SO3. DPPC and DPPG liposomes were prepared to mimic normal and tumor cell membranes. The interaction between Pep-CnV and biomembranes was investigated by the measurements of surface tension and cargo leakage. Results proved Pep-CnV was more likely to interact with the DPPG liposome and destroy its biomembrane under the stimulus of the reductant. And the destruction increased with the length of the hydrophobic tail chain. Pep-CnV showed its potential as an intelligent antitumor agent.
研究领域:
生物化学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Current Pharmaceutical Analysis
·
2018
·Vol. 14
·期 1
·41-52
·
IF 0.859
Sun Congyong,Yuan Yangyang,Omari-Siaw Emmanuel,Tong Shanshan,Zhu Yuan,Wang Qilong,Wang Yuanwen,Wei Qiuyu,Yu Jiangnan,Xu Ximing
Objective: This study aims to establish an efficient, sensitive and specific analytical method (in vitro and in vivo) for syringic acid. Method: Syringic acid loaded liposome was prepared and characterized. In vitro and in vivo chromatographic conditions for the determination of
syringic acid were investigated, with the application verified by pharmacokinetics and biodistribution studies. Results: The developed liposomal formulation produced homogeneous regular, spherical and multilamellar- shaped liposome. Efficient HPLC method for the analysis of syringic acid
was established and validated. The chromatographic separation was performed on a Waters symmetry C18 column (4.6 150 mm, 5 μm) at 25 °C by using mobile phases of 30 % methanol and 70 % acetic acid solution (0.1 %) (in vitro) and 28 % methanol and 72 % acetic acid solution (0.1 %) (in
vivo) at a flow rate of 0.8 mL/min. The wavelength was set at 272 nm. Vanillin was used as internal standard for the in vivo analysis. The established linearity ranges of SA were 1 - 100 μg/mL (R2 = 0.9997) in vitro and 0.125 – 64 μg/mL (R2 = 0.9991) in vivo. In vitro accuracy
of the method was > 99%, and in vivo accuracies were between 91.23 % - 109.54 %, while the precisions met the acceptance criterion. In vivo HPLC method was also confirmed by pharmacokinetics and biodistribution studies. Conclusion: Established HPLC method exhibited high linearity,
precision, accuracy and specificity, could be used for quantitative determination of SA in vitro and in vivo.
研究领域:
药物分析
·
药理学
·
分析化学
✓ 已验证
DOI
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2021
·
IF 13.273
Dandan Chen,Qianqian Liang,Feng Gao,Tianyu Liu,Yunqi Wu,Zhuo Zheng,Jian Kang,Ruizhang Xu,Ya Cao,Ming Xiang
Superior permeability and high selectivity are crucial performances criterion for reverse osmosis (RO) membranes. Inspired by aquaporin-based biomimetic membranes, the loose liposomes as artificial water channels were prepared by thin-layer hydration method with lyso -phospholipids (C14lyso) and cholesterol followed by incorporating liposomes into the polyamide selective layer via in situ interfacial polymerization to fabricate liposomes-based RO membranes (TFC-C14lyso). Stopped-flow tests verified that C14lyso liposomes possess fast water transportability and the effect of C14lyso liposomes on the intrinsic structure of the polyamide selective layer was comprehensively explored. Meanwhile, the structure and performance of the TFC-C14lyso membranes could be regulated by varying the liposome concentrations. As a result, TFC-C14lyso-2 (the concentration of C14lyso liposomes is 0.25 mg/mL) presented an optimal separation performance, showing high water permeance of 3.80 L m −2 h −1 bar −1 and NaCl rejection of 98.6 %. Moreover, the separation mechanism regarding the enhanced permeability of TFC-C14lyso-2 was profoundly revealed via the structure and performance comparison with TFC-DOPC fabricated by incorporating dense DOPC liposomes into its PA selective layer. Building on these studies, our work may provide a facile and versatile pathway for designing advanced membranes in desalination.
研究领域:
生物工程
·
材料科学
✓ 已验证
DOI
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
·
2024
·
IF 4.3
Shulin Shen,Xi Zheng,Xu Dong,Min Fang,Aiqun Wan,Tong Zhu,Qingliang Yang,Jing Xie,Qinying Yan
Methotrexate (MTX) is a first-line drug in treating psoriasis because of its strong anti-proliferation and anti-inflammatory effects. However, systemic administration of MTX will lead to many side effects, such as gastrointestinal irritation, liver and kidney toxicity, etc. Herein, we developed liposome-loaded microneedles (MNs) system to improve transdermal efficiency, which was used to overcome the problems of low transdermal efficiency and poor therapeutic effect of traditional transdermal drug delivery methods. Hyaluronic acid (HA) was modified on the surface of MTX-loaded liposomes. The interaction of HA and CD44 could increase the adhesion of HA-MTX-Lipo to HaCaT cells, thereby promoting the apoptosis or death of HaCaT cells. Results indicated HA-MTX-Lipo MNs could inhibit the development of psoriasis and reduce the degree of skin erythema, scaling, and thickening. The mRNA levels of proinflammatory cytokines such as IL-17A, IL-23, and TNF-α were decreased. The epidermal thickness and proliferative cell-associated antigen Ki67 expression were also reduced. Specifically, the expression of mRNA levels of proinflammatory cytokines was down-regulated. The MNs transdermal delivery of HA-modified-MTX liposomes provided a promising method for treating psoriasis.
研究领域:
药剂学
·
皮肤病学
·
生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）