MOLECULAR PHARMACEUTICS
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2023
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IF 4.9
Kehong Dong,Mei Zhang,Ying Liu,Xintao Gao,Xiaochen Wu,Dayong Shi,Chuanlong Guo,Jing Wang
Excessive acetaminophen (APAP) induces excess reactive oxygen species (ROS), leading to liver damage. Pterostilbene (PTE) has excellent antioxidant and anti-inflammatory activities, but poor solubility limits its biological activity. In this study, we prepared PTE-loaded Soluplus/poloxamer 188 mixed micelles (PTE-MMs), and the protective mechanism against APAP-induced liver injury was investigated. In vitro results showed that PTE-MMs protected H2O2-induced HepG2 cell proliferation inhibition, ROS accumulation, and mitochondrial membrane potential destruction. Immunofluorescence results indicated that PTE-MMs significantly inhibited H2O2-induced DNA damage and cGAS-STING pathway activation. For in vivo protection studies, PTE-MMs (25 and 50 mg/kg) were administered orally for 5 days, followed by APAP (300 mg/kg). The results showed that APAP significantly induced injury in liver histopathology as well as an increase in serum aspartate aminotransferase and alanine aminotransferase levels. Moreover, the above characteristics of APAP-induced acute liver injury were inhibited by PTE-MMs. In addition, APAP-induced changes in the activities of antioxidant enzymes such as SOD and GSH in liver tissue were also inhibited by PTE-MMs. Immunohistochemical results showed that PTE-MMs inhibited APAP-induced DNA damage and cGAS-STING pathway activation in liver tissues. For in vivo therapeutic effect study, mice were first given APAP (300 mg/kg), followed by oral administration of PTE-MMs (50 mg/kg) for 3 days. The results showed that PTE-MMs exhibited promising therapeutic effects on APAP-induced acute liver injury. In conclusion, our study shows that the Soluplus/poloxamer 188 MM system has the potential to enhance the biological activity of PTE in the protection and therapeutic of liver injury.
研究领域:
药剂学
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肝脏病学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Journal of Pharmaceutical Innovation
·
2019
·Vol. 15
·期 1
·155-162
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IF 1.452
Huang Zhengwei,Wu Mingjun,Ma Cheng,Bai Xuequn,Zhang Xuejuan,Zhao Ziyu,Huang Ying,Pan Xin,Wu Chuanbin
Objective Solid lipid nanoparticles (SLN) mainly consist of lipids and surfactants. However, the toxicity of surfactant cannot be ignored, as the surfactant may cause unexpected side effect. This study established model SLN with different surfactants, Tween 80 (T80) and poloxamer 188 (P188). It was aimed to establish ultraviolet-visible (UV-Vis) spectroscopy methods for quantifying the contents of T80 and P188 in the model SLN. Methods The model SLN were produced by emulsification-precipitation method, and their particle size distribution was analyzed. The calibration curves for the contents of T80 and P188 were established. Surfactants in the model SLN were extracted by ultrasonication, and UV-Vis spectroscopy methods were utilized for quantification of surfactants in SLN. Results The deviation of precision and accuracy in P188 and T80 assay were acceptable, which indicated the method could be employed in sample quantification. Ten minutes was considered as the optimal ultrasonication time. And the contents of P188 and T80 were successfully measured by the established UV-Vis methods. Conclusion The UV-Vis spectroscopy methods were developed for the quantification of T80 and P188 in the model SLN. It is expected that the methods could be extended to more SLN systems and applied for the quantification of other surfactants.
研究领域:
药剂学
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分析化学
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DOI
高影响因子
CHEMICO-BIOLOGICAL INTERACTIONS
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2023
·
IF 5.1
Xueyan Hou,Yalin Guan,Sisi He,Zeqing Wu,Jintao Bai,Jingjing Xu,Jingwen Wang,Suyue Xu,Huiqing Zhu,Yanyan Yin,Xue Yang,Yongli Shi
Poloxamer 188 is a widely used pharmaceutical excipient, which can be found in a variety of drug formulations. In this study, a novel self-assembled nanoplatform was developed for active targeting of folate receptor-overexpressing triple-negative breast cancer. This platform, FPP NPs, was prepared by the retrofitted poloxamer 188 derivatives, resulting in nanoparticles with an appropriate size (< 100 nm), good stability, and satisfactory biocompatibility. Cellular uptake and in vivo distribution studies showed that the FPP NPs had strong tumor cell uptake and active targeting capabilities. Furthermore, docetaxel (DTX) was loaded into FPP NPs in this research. The resulting DTX/FPP NPs exhibited high drug encapsulation efficiency and drug loading capacity, and could rapidly release DTX under slightly acidic conditions, significantly increasing the antitumor activity of the encapsulated drug both in vitro and in vivo. In addition, DTX/FPP NPs could significantly decrease the hepatotoxicity and nephrotoxicity of DTX. Therefore, this drug delivery nanoplatform, based on retrofitted poloxamer 188 with self-assembly properties in aqueous solution and active targeting capabilities to tumors, may provide a promising approach for targeted treatment of triple-negative breast cancer.
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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药物递送系统
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DOI
PubMed
高影响因子
JOURNAL OF MATERIALS RESEARCH
·
2022
·Vol. 38
·期 2
·337-349
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IF 2.909
Ren Jin,Liang Liang,Yang Yongqing,Liu Xiang,Li Weidong,Liu Wenbo,Wang Yali,Yu Jingmou
Layered Double Hydroxide (LDHs) requires surface functionalization to achieve desirable colloidal and biological stability for effective drug delivery. The present work reported a new functionalized approaches to construct drug-loaded nanohybrids (2:1E and 2.8:1E) by co-assembling LDH sheets, penta-fluorouracil (5Fu) and poloxamer 188 through exfoliation reassembling. Some analysis showed that more poloxamer 188 were needed to prepare 2:1E with appropriate particle size than 2.8:1E. Besides, 2.8:1E shows advantages in drug loading rate and dispersion as compared with ion exchange method. In addition, these nanohybrids can improve the sudden release of 5Fu in naked drug-loaded LDH. Most importantly, significant enhanced cell uptake and better cytotoxicity were seen in these nanohybrids in contrast to naked drug-loaded LDH. Lastly, the results reveal that assembling drug-loaded LDH with poloxamer 188 is a promising strategy to improve cellular uptake and in vitro efficacy of LDHs for biomedical applications. Graphical abstract Drug-loaded nanohybrids were synthesised by co-assembling LDH sheets, penta-fluorouracil (5Fu) and poloxamer 188 through exfoliation reassembling, and showed advantages in dispersion, enhanced cell uptake and better cytotoxicity as compared with naked drug-loaded-LDH prepared by ion exchange method.
研究领域:
药剂学
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生物材料
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纳米医学
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产品关联
DOI
高影响因子
AAPS PHARMSCITECH
·
2024
·Vol. 25
·期 6
·1-15
·
IF 3.4
Chen Jiasheng,Chen Zhenzhen,Wang Wentao,Wang Liyang,Zheng Jiaqi,Wu Shiqiong,Pan Yuru,Li Sai,Zhao Jie,Cai Zheng
Some glycoside drugs can be transported through intestinal glucose transporters (IGTs). The surfactants used in oral drug preparations can affect the function of transporter proteins. This study aimed to investigate the effect of commonly used surfactants, Poloxamer 188 and Tween 80, on the drug transport capacity of IGTs. Previous studies have shown that gastrodin is the optimal drug substrate for IGTs. Gastrodin was used as a probe drug to evaluate the effect of these two surfactants on intestinal absorption in SD rats through pharmacokinetic and in situ single-pass intestinal perfusion. Then, the effects of the two surfactants on the expression of glucose transporters and tight-junction proteins were examined using RT-PCR and western blotting. Additionally, the effect of surfactants on intestinal permeability was evaluated through hematoxylin-eosin staining. The results found that all experimental for Poloxamer 188 (0.5%, 2.0% and 8.0%) and Tween 80 (0.1% and 2.0%) were not significantly different from those of the blank group. However, the AUC (0-∞) of gastrodin increased by approximately 32% when 0.5% Tween 80 was used. The changes in IGT expression correlated with the intestinal absorption of gastrodin. A significant increase in the expression of IGTs was observed at 0.5% Tween 80. In conclusion, Poloxamer 188 had minimal effect on the drug transport capacity of IGTs within the recommended limits of use. However, the expression of IGTs increased in response to 0.5% Tween 80, which significantly enhanced the drug transport capacity of IGTs. However, 0.1% and 2.0% Tween 80 had no significant effect. Graphical Abstract
研究领域:
药剂学
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药理学
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肠道吸收
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产品关联
DOI
PubMed
高影响因子
PHARMACEUTICAL CHEMISTRY JOURNAL
·
2021
·Vol. 54
·期 10
·1033-1039
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IF 0.837
Shi Xiangjun,Ding Zejie,Bao Jiayin,Wang Chao
Solid dispersions (SDs) containing co-carrier were developed to improve in vitro dissolution and in vivo pharmacokinetics of celecoxib (CXB). Various polymers, including PVP K30, PEG4000, PEG6000, Poloxamer 188, Eudragit E100 and colloidal SiO 2 , were studied in the preparation of CXB-containing SDs. Poloxamer 188 and Aerosil stood out in preliminary characterization. Further study was focused on the selection and characterization of optimum ratio of CXB and polymer in solid dispersions (CXB-Poloxamer 188-Aerosil, 1:5:1). Results exhibited remarkable enhancement of both the dissolution and bioavailability of CXB which retained an amorphous form in SD samples.
研究领域:
药学
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药理学
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药物递送系统
✓ 已验证
DOI
高影响因子
PHARMACEUTICAL DEVELOPMENT AND TECHNOLOGY
·
2023
·
IF 3.4
Liang Liang,Jin Ren,Jun Dai,Jianyun Liu,Lifang Zhang,Donglin Li,Chao Yang,Jingmou Yu
Exploitation of advanced methotrexate (MTX) delivery with nanocomposites has important clinical application value. Poloxamer 188 micelle and layered double hydroxide loaded with MTX (LDH-MTX) by exfoliation reassembling were used to prepare LDH-MTX-poloxamer 188 nanocomposites with good dispersibility and efficient cellular uptake for controlled drug delivery. The LDH-MTX-poloxamer 188 nanocomposites with sphere-like morphology, of which the average hydrodynamic diameter was <100 nm, were shown to have better dispersion state than naked LDH-MTX. Importantly, the LDH-MTX-poloxamer 188 nanocomposites could achieve significant sustained drug release and have obvious pH dependent responsive release ability. In addition, these nanocomposites also exhibited long-term and excellent in vitro antitumor efficacy as opposed to pure MTX or LDH-MTX as evident from cell viability. More interestingly, compared to pure FITC used to simulate MTX, LDH nanocomposites labeled with FITC were considered to have better cell adhesion through cell uptake. Therefore, the studied nanocomposites of LDH-MTX-poloxamer 188 can be further used as a new advanced MTX delivery nanovehicles with desired properties in future therapeutic aspects.
研究领域:
药剂学
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纳米医学
·
肿瘤学
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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）