JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2020
·
IF 3.209
Baolin Wang,Yimeng Lu,Rong Wang,Shumeng Liu,Xiaolong Hu,Hao Wang
Amentoflavone, a kind of biflavonoid existing in several medicinal plants such as Selaginella moellendorfi and Gingko biloba , possesses anti-inflammatory, antioxidant, anti-virus, anti-tumor activities. In the present study, a new reliable and sensitive UHPLC-ESI-MS/MS method was developed to determine the permeability of amentoflavone under different conditions, and its metabolites in Caco-2 cells were identified by means of UHPLC-Q-TOF-MS/MS method. The results showed that amentoflavone could be considered as a compound with moderate intestinal absorption in Caco-2 cell model and its absorption characteristics might be involved in paracellular passive penetration and clathrin-mediated endocytosis with no participation of efflux transporters. Eight metabolites of amentoflavone were identified in Caco-2 cell model, indicating that the main metabolic pathways were oxidation, reduction, methylation and glucuronide conjugation. This study can provide valuable evidence for an in-depth understanding of absorption mechanism and transformation of amentoflavone in the intestine.
研究领域:
药理学
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分析化学
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生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING RESEARCH & DESIGN
·
2025
·
IF 3.9
Ying Zhang,Jingjing Liu,Ling Yin,Chengyun Yan,Bingli Jiang,Yueyi Deng
The cocrystals of Indomethacin (Imc) with isonicotine (Iso), isoniazid (Inh), and salicylic acid (Sa) were prepared to improve solubility, dissolution rate, and in vivo intestinal absorption. The prepared cocrystals were characterized by X-ray diffraction (XRPD), differential scanning calorimetry (DSC), thermogravimetric analysis (TG), and Fourier infrared spectroscopy (FTIR). Subsequently, the equilibrium solubility and in vitro dissolution of the cocrystals were evaluated. The results indicate that the equilibrium solubility of the Imc-Inh cocrystal is 3.2 times that of Imc, and the maximum dissolution of the Imc-Iso cocrystal is approximately 4 times that of Imc. The mechanism underlying the formation of the Imc-Iso, Imc-Inh, and Imc-Sa cocrystals was investigated through the thermodynamics of the cocrystal formation and the calculation of DFT-D. The results demonstrate that the Gibbs free energy change (ΔG), the formation enthalpy change (ΔH) of the Imc cocrystals with Iso, Inh, and Sa are less than zero, indicating that the formation of cocrystals is spontaneous and driven by enthalpy. As the temperature rises, the values of ΔG of the cocrystals formation demonstrate a gradual increase, indicating that elevated temperatures are not favorable to cocrystal formation. In vivo single-pass intestinal perfusion experiments (SPIP) reveal that the Imc-Iso cocrystals can enhance the permeability of Imc.
研究领域:
药学
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物理化学
✓ 已验证
产品关联
DOI
高影响因子
Biomaterials Research
·
2025
·
IF 9.6
Zijian Dai,Wanting Yin,Jiahao Li,Lingjun Ma,Fang Chen,Qun Shen,Xiaosong Hu,Yong Xue,Junfu Ji
Quercetin as a flavonoid polyphenol in nature has shown great anti-obesity effects. Due to its poor stability in chemical structure and low intestinal absorption, the in vivo bioavailability of quercetin is considered to be the main challenge for applications. To achieve the oral quercetin administration, chitosan was successfully trimethylated (TMC) to coat the quercetin-loaded zein nanoparticles (Zein-Q), which were designed as the core–shell structure for enhancing the intestinal absorption in this study. TMC-Zein-Q was demonstrated to protect quercetin from degradation and showed the sustained-release effect in an in vitro drug release experiment. The nanoparticles were found to reversibly open tight junctions between intestinal epithelial cells and help to increase quercetin uptake via the paracellular pathway in Caco-2 cells. In addition, the delivery system also showed stronger intestinal permeability and mucoadhesion in vivo, which improved the bioavailability of quercetin in cellular and animal experiments. After 10 weeks of intervention, TMC-Zein-Q could effectively suppress weight gain, improve serum lipid levels, and ameliorate hepatic steatosis and glucose tolerance in high-fat diet (HFD) mice by mediating the AMPK pathway. Consequently, this work successfully constructed TMC-Zein-Q for oral quercetin delivery, providing a novel and feasible strategy for the treatment of obesity via the oral route.
研究领域:
药剂学
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营养学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
·
2021
·
IF 4.384
Kunkun Guo,Xin Wang,Baolin Huang,Xiaoyun Wu,Shuimei Shen,Zimin Lin,Jie Zhao,Zheng Cai
Gastrodin is the main active constituent of Tianma, a famous traditional Chinese herbal medicine. Our previous research has found that gastrodin is absorbed rapidly in the intestine by the sodium-dependent glucose transporter 1 (SGLT1). In the current report, gastrodin is the best glycoside compound absorbed via the glucose transport pathway. This study aimed to investigate the effect of the slight difference in chemical structure on the drug intestinal absorption via the glucose transport pathway. Traditional biopharmaceutical and computer-aided molecular docking methods were used to evaluate the intestinal absorption characteristics of three gastrodin analogues, namely, salicin , arbutin and 4-methoxyphenyl-β-D-glucoside (4-MG). The oil–water partition coefficient (log P ) experiments showed that the log P values of the gastrodin analogues followed the order: 4-MG > salicin > arbutin. In vitro Caco-2 cell transport experiments demonstrated that the apparent permeability coefficient ( P app ) value of arbutin was higher than those of salicin and 4-MG. In situ single-pass intestinal perfusion experiments showed that the absorption of arbutin and 4-MG was better than that of salicin and that the absorption of the three compounds in the colon was lower than that in the small intestine. Quantitative real-time polymerase chain reaction results confirmed that the SGLT1 mRNA expression in the small intestine of rats was obviously higher than that in the colon of rats. In vivo pharmacokinetic experiments demonstrated that the oral bioavailability of salicin was lower than those of arbutin and 4-MG. In vitro and in vivo experiments showed that glucose or phlorizin (SGLT1 inhibitor) could decrease the intestinal absorption of the three compounds. Contrary to the above biopharmaceutical experiments, the computer-aided molecular docking test showed that the affinity of salicin to the v SGLT receptor was stronger than those of arbutin and 4-MG. In conclusion, the SGLT1 can facilitate the intestinal absorption of salicin, arbutin and 4-MG, and the slight difference in chemical structure can affect absorption.
研究领域:
药理学
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生物医学工程
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中药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DRUG DELIVERY
·
2015
·
IF 2.558
Hailong Zhang,Xiaoyan Huang,Ya Sun,Jianfeng Xing,Akira Yamamoto,Yang Gao
Effects of chitosan oligomers with different types and varying concentrations on the intestinal and pulmonary absorptions of calcitonin were investigated in rats by an in situ closed loop method and an in vivo pulmonary absorption experiment, respectively. Various chitosan oligomers demonstrated different efficiencies in improving the intestinal and pulmonary absorptions of calcitonin, and chitosan hexamer with the optimal concentration of 0.5% (w/v) showed the greatest absorption enhancing effect. Moreover, pharmacodynamic parameters of calcitonin after its coadministration intrapulmonarily with various chitosan oligomers were consistently larger than that in the intestinal delivery, indicating the superior potential of pulmonary administration for systemic delivery of calcitonin. Furthermore, various chitosan oligomers neither obviously increased release amounts of protein nor activities of lactate dehydrogenase (LDH) in bronchoalveolar lavage fluid (BALF), revealing the safety of these chitosan oligomers to lung tissue. In addition, bioadhesions of various chitosan oligomers were well consistent with their absorption enhancing effects in the absorption experiment, suggesting the contribution of mucoadhesive properties of chitosan oligomers to their absorption improving effects. Taken together, chitosan oligomers, especially chitosan hexamer, can effectively improve the intestinal and pulmonary absorptions of calcitonin partly due to the mucoadhesion between positive chitosan oligomers and negative mucus in the membrane.
研究领域:
药剂学
·
药物递送
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2022
·
IF 10.723
Chengtao Han,Li Fang,Shixin Song,Weihong Min
A polysaccharides-based delivery system was designed to encapsulate and control the release of peanut peptide (PP). The PP-loaded polyelectrolyte complex (TMC-PP-SA) was fabricated based on the electrostatic self-assembly between n-trimethy chitosan (TMC) and sodium alginate (SA). The complex exhibited uniform spherical morphology, satisfactory stability and high encapsulation efficiency. In vitro release behavior indicated that TMC-PP-SA polyelectrolyte complex could inhibit the release of PP at simulated gastric medium and enhance the release of PP at simulated intestinal medium. Moreover, the antioxidant activity of PP after encapsulation was significantly improved compared with that of directly digested PP. Ex vivo intestinal permeation study confirmed that about 41.76 ± 1.43% PP in TMC-PP-SA could be absorbed in the intestinal. The cytotoxicity measurement indicated that the fabricated TMC-PP-SA polyelectrolyte complex was biocompatible and nontoxic. Therefore, these results indicated that the polysaccharides-based delivery system had great potential in protecting active peptides from degradation and facilitating their absorption.
研究领域:
食品科学
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生物技术
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药剂学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
AMERICAN JOURNAL OF CHINESE MEDICINE
·
2025
·Vol. 53
·期 02
·543-566
·
IF 5.5
Jia-Yuan He,Fu-Lan Xiao,Qin-Yue Zheng,Chang-Hong Wang,Yi-Yue Tang,Jun-Xuan Fu,Jia-Yi Huang,Lian-Di Zhou,Qi-Hui Zhang
The intestinal absorption of active herbal constituents plays an important role in the biomedical efficacy of Traditional Chinese Medicine (TCM) formulations after oral administration. TCM compounds with low oral bioavailability can reach the distal intestine and then interact with intestinal flora, influencing the botanical pharmacological effects. In this study, in vitro digestion and an ex vivo Ussing chamber model were utilized to evaluate the intestinal absorption behavior of Forsythiae Fructus - Lonicerae Japonicae Flos -containing Yinqiao Jiedu Granule (YQJDG). It was found that the jejunum exhibited active absorption effects for some components of the formula, while the oral bioavailability of other herbal ingredients was low. Through further research using a combined UPLC-MS/MS and 16S rDNA sequencing technique, we studied the existence of the reciprocal interactions between YQJDG and gut microbiome. The in vitro fecal fermentation results showed that YQJDG significantly impacted the microbial community composition. The YQJDG markedly increased the abundance of beneficial microorganisms, such as Parabacteroides distasonis and Streptococcus gallolyticus subsp. Macedonicus, and suppressed the abundance of conditional pathogens including Prevotella steorerea, Haemophilus parainfluenzae , and Bacteroides . These effects may potentially contribute to the body’s immune functions and anti-inflammatory capacities. UPLC-MS/MS analysis suggested that the fecal microbiota chemically transformed constituents with low bioavailability to more readily absorbed potentially active metabolites. These findings provided valuable insights into the absorption characteristics of YQJDG and its interaction with the gut microbiome, further facilitating our understanding of precise pharmacological mechanisms of action of this Chinese herbal formulation.
研究领域:
中药学
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微生物学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF MICROENCAPSULATION
·
2019
·
IF 2.04
Ran Li,Rui Bao,Qiu-Xuan Yang,Qi-Long Wang,Michael Adu-Frimpong,Qiu-Yu Wei,Toreniyazov Elmurat,Hao Ji,Jiang-Nan Yu,Xi-Ming Xu
Aims: The aim was to improve the absorption and bioavailability of [6]-shogaol with β-cyclodextrin (β-CD) prior to in vitro and in vivo evaluation.Methods: [6]-Shogaol/β-CDs inclusion complexes (6-S-β-CDs) were developed using saturated aqueous solution method and characterised with appropriate techniques. The absorption and bioavailability potential of [6]-shogaol was evaluated via in vivo pharmacokinetics and in situ intestinal perfusion.Results: The results of characterisation showed that 6-S-β-CDs (drug loading, 7.15%) were successfully formulated. In vitro release study indicated significantly improved [6]-shogaol release. Pharmacokinetic parameters such as Cmax, AUC0–36 h, and oral relative bioavailability (about 685.36%) were substantially enhanced. The in situ intestinal perfusion study revealed that [6]-shogaol was markedly absorbed via passive diffusion in the intestinal segments, and duodenum followed by ileum and jejunum.Conclusions: Cyclodextrin inclusion technology could enhance the intestinal absorption and oral bioavailability of hydrophobic drugs like [6]-shogaol.
研究领域:
药剂学
·
药物代谢动力学
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生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE
·
2025
·
IF 3.5
Lijun Su,Zhipeng Yu,Wenzhu Zhao
BACKGROUND This study aimed to elucidate the transport mechanism of lycopene-loaded nanomicelles to improve intestinal absorption of lycopene. The interactive mechanism between lycopene and nanomicelles was investigated through isothermal titration calorimetry (ITC). The cytotoxicity, cellular uptake, endocytosis, and intracellular transport pathways of lycopene-loaded nanomicelles were investigated using the Caco-2 cell model. RESULTS The ITC results demonstrated that nanomicelles/lycopene binding was an entropy-driven spontaneous exothermic reaction, and hydrophobic interactions were the main driving force. Lycopene-loaded nanomicelles were not cytotoxic, and uptake of lycopene by Caco-2 cells increased 2.20-fold after nanoencapsulation. The results of intracellular transport of lycopene-loaded nanomicelles indicated that the endoplasmic reticulum, Golgi apparatus, and lysosomes play key roles in this process. The intracellular transport results showed that the endoplasmic reticulum, Golgi apparatus, and lysosomes were important organelles for intracellular transport of lycopene-loaded nanomicelles. CONCLUSION Nanomicelles effectively enhance the cellular uptake of lycopene and are promising carriers for its delivery. This study contributes to the understanding of the transport mechanism of nanomicelles through intestinal epithelial cells. © 2025 Society of Chemical Industry.
研究领域:
营养学
·
生物化学
·
药剂学
✓ 已验证
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2019
·Vol. 8
·期 8
·1800934
·
IF 6.27
Yuan Liu,Dan Chen,Jialin Li,Dengning Xia,Miaorong Yu,Jinsong Tao,Xinxin Zhang,Li Li,Yong Gan
Gene vectors for oral delivery encounter harsh conditions throughout the gastrointestinal tract, and the continuous peristaltic activity can quickly remove the vectors, leading to inefficient intestinal permeation. Therefore, vectors have demanding property requirements, such as stability under various pH and, more importantly, efficient uptake in different intestinal segments. In this study, a functional polymer, cholesterol-grafted poly(β-amino ester) (poly[hexamethylene diacrylate-β-(5-amino-1-pentanol)] (CH-PHP)), is synthesized and electrostatically interacted with plasmid DNA to form a CH-PHP/DNA complex (CPNC). This complex is designed to target the Niemann–Pick C1-like receptor, a cholesterol receptor, to improve oral gene delivery efficacy. With the presence of cholesterol, CH-PHP shows mitigated cytotoxicity, enhanced enzyme resistance, and improved gene condensing ability. CPNC further contributes to ≈43.1- and 2.3-fold increases in luciferase expression in Caco-2 cells compared with PNC and Lipo 2000/DNA complexes, respectively. In addition, the in vivo transfection efficacy of CPNC is ≈4.1-, 2.1-, and 1.6-fold higher than that of Lipo 2000/DNA complexes in rat duodenum, jejunum, and ileum, respectively. Therefore, CPNC may be a promising delivery vector for gene delivery, and using a cholesterol-specific endocytic pathway can be a novel approach to achieve efficient oral gene transfection.
研究领域:
药剂学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2024
·
IF 10.5
Yingnan Zhu,Ruikang Zhang,Wenwen Gao,Fei Li,Mei Yang,Jie Feng,Yalan Ji,Jiahang Si,Xiangrong Wang,Yuze Dong
Oral insulin delivery is considered a revolutionary alternative to daily subcutaneous injections in terms of compliance and convenience. However, significant challenges remain in terms of inactivation in gastrointestinal environment and limited permeation across the intestinal epithelium. Herein, we used acid-resistant metal-organic framework (PCN-222) to load insulin and modified the exterior with sodium dodecyl sulfate (SDS) to achieve efficient oral insulin delivery. The PCN-222 nanocarrier with ordered mesoporous cage structure and suitable pore size achieved a high insulin loading of 75 %. The SDS on the surface of nanocarrier reduces its hydrophilicity while reversibly altering cell morphology and increasing epithelial cell permeability, thereby promoting intestinal epithelial absorption. The constructed particle (I@P@S) was encapsulated in sodium alginate (SA) microspheres to protect it from gastric acid degradation and releases it upon entry into the intestinal tract. Through an uptake pathway dominated by clathrin-mediated endocytosis, the released I@P@S realized efficient intestinal permeability and controlled insulin release under physiological conditions due to the phosphate sensitivity of PCN-222, leading to an in vivo bioavailability of 12.9 %. This work provides a valuable reference for the design of oral insulin delivery systems.
研究领域:
药剂学
·
生物医学工程
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOOD CHEMISTRY
·
2024
·
IF 8.5
Mian Wei,Huipeng Zhu,Qiang Zhang,Dawei Gao,Lu Wang,Xiaoyu Li
In order to elucidate the digestion, absorption and metabolism mechanism, Hohenbuehelia serotina polysaccharides were successfully labelled by fluorescein isothiocyanate (FITC-Tyr-HSP), with the fluorescent substitution degree of 0.37 %. FITC-Tyr-HSP with excellent physiological stability possessed the significant fluorescent characteristics, which could be dynamically monitored by in vivo fluorescence imaging and high performance gel permeation chromatography-fluorescence detector (HPGPC-FLD). Through investigation of gastrointestinal digestion in vitro , the degradation of HSP was only occurred in small intestinal fluid. The results of in vivo studies also confirmed that a small amount of HSP were degraded in small intestine, and then absorbed by intestinal epithelial cells to enter into the bloodstream, reaching to liver, spleen and kidney. Meanwhile, most of HSP that could not be digested were directly transported to cecum and colon, where they were metabolized by gut microbiota to produce SCFAs, with the total content of which reached to 60.52 mmol/L after gavage for 24 h. Ultimately, the polysaccharides were excreted from the body mainly by feces and urine pathways. This study is meaningful for providing a practical basis to elucidate the digestion, absorption and metabolism of polysaccharides.
研究领域:
食品科学
·
营养学
·
微生物学
✓ 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）