FOOD RESEARCH INTERNATIONAL
·
2025
·
IF 8
Linlin He,Lan Zhang,Fanyi Meng,Jingge Wei,Fei Chen,Siqi Qin,Ge Jin,Hailong Cao
Intestinal senescence, often characterized by increased oxidative stress, is linked to gastrointestinal disorders such as inflammatory bowel disease and colorectal cancer. While previous studies have suggested that diets rich in food additives, such as the emulsifier Polysorbate 80 (P80), may influence gut health, the impact of P80 exposure on intestinal senescence remains unclear. This study aimed to explore the effects of P80 on intestinal senescence in a senescence-accelerated mouse prone model. The results revealed that P80 exposure could damage the intestinal barrier, induce oxidative stress, and accelerate intestinal senescence. Mechanistically, P80 activated the peroxisome proliferator-activated receptor-α (PPARα) and fatty acid-binding protein 1 (FABP1) axis, increasing intestinal fatty acid absorption and triggering lipotoxicity, which promoted senescence. Additionally, P80 exacerbated D-galactose-induced epithelial cell senescence and lipid accumulation via the PPARα signalling pathway. Importantly, the PPARα antagonist GW6471 mitigated fatty acid uptake and reduced senescence in the intestine. In conclusion, the emulsifier P80 accelerated intestinal senescence by regulating the PPARα-FABP1 axis to induce intestinal fatty acid uptake and lipotoxicity, suggesting new insights into the adverse effects of food additives on gut health.
研究领域:
营养学
·
分子生物学
·
胃肠病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MICROCHEMICAL JOURNAL
·
2020
·
IF 3.594
Zhongping Huang,Chaochao Tu,Huijun Liu,Lili Wang,Zuoyi Zhu,Ichi Watanabe
An on-line two-step pyrolytic methylation technique combined with gas chromatography was developed for rapid analysis of free and bonded fatty acids in Polysorbate 80 respectively. Free fatty acids in Polysorbate 80 were transformed to their corresponding fatty acid methyl esters in the presence of tetramethylammonium acetate (TMAAc) in the first step with a vertical microfurnace pyrolyzer at 300 °C. After the analysis of free fatty acids, bonded fatty acids were then transformed into methyl esters in the presence of tetramethylammonium hydroxide (TMAH) at 300 °C. The effects of pyrolytic methylation temperature, TMAAc concentration and ratio to Polysorbate 80 were evaluated. The range of linearity, reproducibility, the detection limits (LODs), and the quantitation limits (LOQs) were also investigated using linoleic (C18:2), oleic (C18:1), stearic (C18:0) acids. The recoveries ranged from 92.2 to 105.0%. The RSDs of intra-day and inter-day precision were in the range of 2.89–5.9% (n = 6) and 4.4–7.2% (n = 3) respectively. Compositions of free and bonded fatty acids in five Polysorbate 80 samples were analyzed respectively to evaluate the feasibility of the proposed method. The results prove that the proposed method is simple, solvent saving and environmentally friendly since it avoids off-line derivatization and solvent extraction, and has a potential application in the high quality control of Polysorbate 80.
研究领域:
分析化学
·
药物分析
·
食品科学
✓ 已验证
产品关联
DOI
高影响因子
ACS Applied Nano Materials
·
2024
·
IF 5.3
Rujing Xu,Ying Lu,Mengxiao Liu,Yanzhao Yin,Junsheng Zhao,Lin Wu,Song Shen
Oral delivery of insulin exhibits low bioavailability due to the hydrolysis in acidic gastric juice, biodegradation of enzymes, and inefficient penetration through the intestinal mucus and epithelial cell layer. Here, we report a micelle platform to enhance the oral delivery of insulin. Insulin was precipitated by zinc ions to form hydrophobic nanoparticles and subsequently coated with a surfactant polysorbate-80 (Tween-80) to form nanosized micelles (TW-Zn-rhINS). Tween-80 protects the insulin from the degradation of enzymes, meanwhile facilitating the diffusion within mucus and the epithelial cell layer by opening the tight junctions. The micelles were then lyophilized and encapsulated in enteric capsules to overcome acidic hydrolysis in gastric juice. The micelles significantly increased transcellular insulin transport and uptake. The in vivo experiments demonstrated that oral TW-Zn-rhINS micelle capsules (30 IU/kg) decreased the blood glucose of diabetic mice by 58.74% after administration for 6 h, while the postprandial blood glucose dropped by 51.1%. Pharmacokinetics data indicated that the relative oral bioavailability of TW-Zn-rhINS was 7.88%, which was 7.73 times higher than that of insulin. The micelles present a promising platform to enhance the oral bioavailability of insulin, also indicating a potential for oral delivery of protein.
研究领域:
药剂学
·
生物医学工程
·
药物代谢动力学
✓ 已验证
产品关联
DOI
高影响因子
Frontiers in Pharmacology
·
2026
·
IF 4.8
Huabing Yuan,Lu Han,Hao Deng,Yue Tan,Yi Yang,Yi Liu,Jiaxin Ying,Mengqi Fang,Hui Wei,Zhihe Tao
Brain-targeted drug delivery remains a major challenge in pharmaceutical research. In this study, four types of polysorbate 80 and cholesterol-modified pullulan polymers (CHPP) were synthesized and self-assembled into nanoparticles (CHPP NPs) for brain drug delivery. The properties of these NPs, including brain targeting efficiency, were systematically evaluated to investigate the influence of polymer modification on their performance. The hydrophobicity of the polymers increased with the degree of cholesterol substitution, which in turn led to a reduction in nanoparticle size. Furthermore, higher hydrophobicity contributed to an increased drug loading capacity for paclitaxel (PTX) and a more sustained drug release profile. In vivo fluorescence imaging revealed that formulations with higher levels of polysorbate 80 and cholesterol modification exhibited significantly enhanced brain targeting efficiency compared to other variants. The PTX-loaded CHPP NPs (PTX-CHPP NPs) demonstrated potent cytotoxicity and inhibitory effects against SJ-GBM2 glioma cells in vitro, underscoring their potential as a promising platform for brain-targeted drug delivery. These findings provide valuable insights for the rational design of brain-targeting nanocarriers.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2023
·
IF 3.4
Ling Bai,Yanlan Zhang,Cai Zhang,Yuchen Lu,Zhiguo Li,Gang Huang,Bo Meng
A study on the polysorbate 80 stability in various formulation buffers commonly used in biopharmaceuticals was performed, to investigate the excipients influence on polysorbate 80 degradation. Polysorbate 80 is a common excipient in biopharmaceutical products. However, its degradation will potentially impact the drug product quality, and may trigger protein aggregation and particles formation. Due to the heterogeneity of the polysorbates and the mutual effects with other formulation compositions , the study of polysorbate degradation is challenging. Herein, a real-time stability study was designed and performed. The polysorbate 80 degradation trend was monitored by fluorescence micelle-based assay (FMA), reversed-phase-ultra-performance liquid chromatography-evaporative light scattering detector (RP-UPLC-ELSD) assay, and LC-MS assay. These assays provide orthogonal results to reveal both the micelle-forming capability and the compositional changes of polysorbate 80 in different buffer systems. The degradation occurred after a period of storage under 25 °C in different trend, which indicates the excipients could impact the degradation kinetics. Upon comparison, the degradation is prone to happen in histidine buffer than in acetate, phosphate or citrate buffers. LC-MS confirms oxidation as an independent degradation pathway with detection of the oxidative aldehyde. Thus, it is necessary to pay more attention to the excipients selection and their potential impact on polysorbate 80 stability to achieve longer shelf life for the biopharmaceuticals. Besides, the protective roles of several additives were figured out, which could be applied as potential industrial solutions to the polysorbate 80 degradation issues.
研究领域:
生物制药
·
药物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Pharmaceutics
·
2025
·Vol. 17
·期 12
·1572
·
IF 5.5
Xiaofeng Wang,Jue Wang,Xia Zhao,Langui Xie,Rui Yang,Chunmeng Sun,Jiasheng Tu,Huimin Sun
Background/Objectives : Polysorbate 80 (PS80), a complex surfactant mixture, is widely recognized for its ability to enhance drug permeation across the blood–brain barrier (BBB). While this effect is generally attributed to the combined actions of its components, the specific contribution and potential selectivity of individual minor components remain poorly understood. This study therefore aimed to isolate and compare the primary minor components of PS80 to determine whether they uniformly enhance BBB permeation or exhibit drug-specific functions. Methods : In this research, four primary minor components of PS80—polyoxyethylene sorbitan monooleate (PSM), polyoxyethylene isosorbide monooleate (PIM), polyoxyethylene sorbitan dioleate (PSD), and a polyethylene glycol/polyoxyethylene sorbitan/polyoxyethylene isosorbide mixture (PEG/PS/PI mixture)—were isolated using preparative liquid-phase chromatography. Drug-loaded formulations were then prepared using the solvent evaporation method incorporating five model drugs: 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindotricarbocyanine iodide (DiR, MW = 1013.39 Da), donepezil (MW = 379.49 Da), nimodipine (MW = 418.44 Da), chlorogenic acid (MW = 354.31 Da), and paclitaxel (MW = 853.92 Da). The permeability of these formulations across the BBB was evaluated in BALB/c mice after intravenous administration. Brain distribution of the lipophilic dye DiR was assessed using fluorescence imaging, whereas brain homogenate concentrations of therapeutic drugs were quantified by UPLC-MS/MS. Results : Results revealed that the enhancement of brain delivery was dependent on both the specific minor component and the drug. The PEG/PS/PI mixture specially enhanced the brain homogenate concentration of donepezil to 11.8 ± 1.2 ng/mL, representing a 6.9-fold enhancement, while PIM micelles increased the delivery of DiR, donepezil, and nimodipine. In contrast, PSM and PSD micelles improved transport of only DiR and donepezil. The broad performance of PIM suggests a more flexible formulation—a hypothesis that warrants further validation. Conversely, none of the different minor components enhanced the delivery of chlorogenic acid or paclitaxel, underscoring the critical role of specific drug–component interactions. Conclusions : This component-resolved insight challenges the conventional perception of PS80 and provides a rational framework for engineering precision brain-targeted delivery systems by selecting functional minor components.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHROMATOGRAPHIA
·
2018
·Vol. 81
·期 4
·669-675
·
IF 1.401
Huang Zhongping,Qiu Ruofeng,Huang Yilei,Liu Huijun,Pan Zaifa,Wang Lili
A novel method of on-line pyrolytic methylation–gas chromatography was developed for the rapid analysis of fatty acid composition in Polysorbate 80 without any tedious pre-treatment steps. Fatty acids in Polysorbate 80 were converted into their corresponding fatty acid methyl esters in the presence of trimethylsulfonium hydroxide with a vertical microfurnace pyrolyzer at 300 °C. The premixing procedure of sample and organic alkali reagent was necessary before the on-line pyrolytic methylation to improve the repeatability. The relative standard deviations for peak areas of fatty acids in Polysorbate 80 were over the range of 0.3–9.1% ( n = 5). Six Polysorbate 80 samples, consisting of three samples of pharmaceutical grade and three samples of non-pharmaceutical grade, were analyzed to evaluate the feasibility of the proposed method. The relative percentages (%) of fatty acids for samples of pharmaceutical grade meet the Chinese Pharmacopoeia requirements with the amount of oleic acid varying from 78.4 to 89.3%. On the other hand, the relative percentages (%) for palmitic acid and stearic acid in samples of non-pharmaceutical grade were out of the specification limits, with the amount of oleic acid varying from 62.0 to 63.5%. The quantitative results determined by on-line pyrolytic methylation were in agreement with those obtained by off-line methylation. The result proved that gas chromatography with on-line pyrolytic methylation technique is of great value for rapid screening analysis of Polysorbate 80 samples in bulks.
研究领域:
分析化学
·
药学
✓ 已验证
产品关联
DOI
高影响因子
ANALYTICAL CHEMISTRY
·
2023
·
IF 7.4
Xinjian Li,Zhe Wang,Bowen Zheng,Yanan Wang,Jinlan Zhang
Polysorbate 80 (PS80) is widely used as an excipient in vaccines and biopharmaceuticals. The oxidized species of PS80 have raised concern because of their potential to compromise product stability and pose a clinical risk. Analytical methods to profile and identify the oxidized species are hard to develop owing to their complexity and low abundance. Herein, a novel strategy was demonstrated to comprehensively profile and identify the oxidized species of PS80 using ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. The characteristic fragmentation patterns of the oxidized species were obtained under the “all ions” scan mode. Then, 10 types of distinct fragments from oxidized oleates were identified and confirmed using two purified oxidized species (polyoxyethylene (POE) sorbitan mono-hydroxy oleate and POE mono-keto oleate) whose structures were elucidated via nuclear magnetic resonance. A total of 348 (32 types) oxidized species were profiled and identified in the oxidized PS80 samples, including 119 (10 types) species found for the first time to our knowledge. Mathematical models were established and validated based on the good logarithmic relation between the POE degree of polymerization and the relative retention time and used to rapidly discover and identify the oxidized species. A novel strategy was established to profile and identify the PS80 oxidized species based on their retention time, HRMS, and HRMS2 data of the detected peaks using an in-house dataset. Using this strategy, 104 (14 types) and 97 (13 types) oxidized species were identified for the first time in PS80 and its preparations, respectively.
研究领域:
药物分析
·
生物制药
✓ 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）