COLLOIDS AND SURFACES B-BIOINTERFACES
·
2023
·
IF 5.8
Jie Huang,Xiao Tang,Ziqiong Yang,Jianqiu Chen,Kun Wang,Chengnan Shi,Zihan Liu,Ming Wu,Qian Du
Irinotecan (CPT-11) is used as a first or second-line chemotherapy drug for the treatment and management of colorectal cancers. In vitro studies have shown that 7-ethyl-10-hydroxycamptothecin (SN38), the active metabolite of CPT-11, displays promising anticancer efficacy. However, its poor aqueous solubility and hydrolytic degradation result in its lower oral bioavailability and impracticable clinical application. To overcome these limitations, a novel amphiphilic chitosan derivative, deoxycholic acid decorated N’-nonyl-trimethyl chitosan, was synthesized. Nano-micelles loaded with SN38 were subsequently prepared to enhance the bioavailability and anti-tumor efficacy of the drug through oral administration. The nano-micelles demonstrated improved dilution stability, enhanced greater mucosal adherence, significant P-gp efflux inhibition, and increased drug transport in the intestine by paracellular and transcellular pathways. Consequently, both the in vivo pharmacokinetic profile and therapeutic efficacy of SN38 against cancer were substantially improved via the micellar system . Thus, the developed polymeric micelles can potentially enhance the SN38 oral absorption for cancer therapy, offering prospective avenues for further exploration.
研究领域:
药剂学
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肿瘤学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
PROCESS BIOCHEMISTRY
·
2023
·
IF 4.4
Qi Liu,Shan Shao,Jingyu Bao,Syed Jalil Shah,Shumin Yue,Xinqi Luan,Qing Liu,Linguang Xing,Zhongfeng Shi,Zhenxia Zhao,Zhongxing Zhao
The 3D-QSAR model is one of the most effective techniques for predicting the peptide bioactivity based on their structure properties. The accuracy of model prediction is highly dependent on the bio-activity of the peptides in its dataset. However, the same peptide used for constructing the database was reported to have obviously different activities in different published articles, which may significantly decrease the prediction accuracy. Based on this, we chose ACE inhibitory (ACE-I) dipeptides that can be absorbed directly into the human small intestine as research object. Ten dipeptides were randomly selected from the literatures for molecular docking with ACE and synthesized to test their activity. Ultimately, a linear equation was developed between bio-activities and docking scores, which was used to revalidate the reliable ACE-I activities of all reported dipeptides for constructing a credible dataset of 3D-QSAR model. The prediction accuracy was significantly enhanced and the model we established had a high Q 2 = 0.840 and R 2 = 0.998. Furthermore, dipeptide CW was predicted and tested in vitro to achieve the highest ACE-I activity (IC 50 = 0.16 μM), and the inhibition mechanism was also investigated. This study introduced a new method for predicting bio-activity with high precision using the 3D-QSAR model.
研究领域:
生物信息学
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药物化学
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生物化学
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产品关联
DOI
高影响因子
FOOD RESEARCH INTERNATIONAL
·
2021
·
IF 6.475
Baiyu Zhang,Mengmeng Liu,Gang Liu,Dan Li,Benhong Zhou
The mechanisms of action of polysaccharides in vivo have been widely elucidated. However, the systematic research of its absorption and transport mechanisms remains unclear. Herein, we extracted a polysaccharide fraction (GEP) from Gastrodia elata by water extraction and alcohol precipitation and aimed to reveal its oral absorption processes through animal models and Caco-2 cells monolayer models. Our research data showed that GEP-Cy5.5 could be absorbed through the small intestine and the main absorption intestinal segment was the ileum (the absorption rate constant [Ka]: (3.64 ± 0.70) × 10 −4 cm/s; the effective apparent permeability [Papp value]: (4.88 ± 1.02) × 10 −5 cm/s). The ligated intestinal loops also revealed that GEP-Cy5.5 could pass through the villi of the small intestine and the mucosal barrier into the submucosa. Furthermore, GEP-Cy5.5 was readily absorbed into the blood through the gastrointestinal tract, then distributed in the liver and the kidney. The Papp value of in vitro transport study was (1.29 ± 0.08) × 10 −6 cm/s, which was a time-dependent process. Notably, GEP-Cy5.5 was transported through the endocytosis process mediated by clathrin and macropinocytosis. The underlying absorptive mechanisms of GEP in vivo and in vitro were clarified, which provided the guidance for clinical medicine administration and could deepen the biological understanding of oral polysaccharides.
研究领域:
药理学
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生物化学
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DOI
PubMed
高影响因子
FOOD CHEMISTRY
·
2025
·
IF 9.8
Ruihong Dong,Yuting Wang,David Julian McClements,Qiang Yu,Jianhua Xie,Huijie Zhang,Lizhi Huang,Bin Li,Jinlong Tian,Yi Chen
This study investigated intestinal absorption and cellular antioxidant efficacy of anthocyanin (ACN)-loaded ovalbumin (OVA)-carrageenans (ι-, λC)/dextran sulfate (DS) nanocomplexes. Utilizing Caco-2 cells, we assessed endocytic pathways, intracellular trafficking, and delivery efficacy of ternary nanocomplexes. ACN-loaded nanocomplexes could be internalized by cells in a time-, dose-, energy-dependent manner, with macropinocytosis, lipid raft/caveolae, and actin co-mediated endocytosis routes playing pivotal roles. Nanocomplexes inhibited P-glycoprotein efflux of Rhodamine-123, enhancing the apparent permeability of ACN into cells, especially for OVA-ιC-ACN. Transport pathways of ACN-loaded nanocomplexes through Caco-2 monolayers involved different organelles including microtubules, Golgi complexes, endoplasmic reticulum, and lysosomes. Compared to free ACN, nanocomplexes exhibited more efficiency in recovering cellular viability and endogenous antioxidant enzyme activities under oxidative stress. Our findings provide a more comprehensive understanding of internalization, transport mechanisms of protein-polysaccharide-anthocyanin nanocomplexes across epithelial cell monolayers, and provide valuable insights for designing efficient ACN-loaded nanocomplex systems with high transportation efficiency and intestinal absorption.
研究领域:
生物化学
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药剂学
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细胞生物学
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营养学
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产品关联
DOI
PubMed
高影响因子
Current Pharmaceutical Analysis
·
2022
·Vol. 18
·期 2
·199-207
·
IF 0.743
Yang Ping,Luo Jinhua,Yan Shuo,Li Xiaohong,Yao Qian
Background: Cyclodextrins (CDs) are commonly used host molecules of inclusion complex. However, due to the lack of a sensitive determination method, the absorption process of CDs remains unclear. Objective: In this study, an oleuropein (OL) inclusion complex employing hydroxylpropyl-betacyclodextrin
(HP-beta-CD) as host molecules was prepared and the formation of inclusion complex was ascertained by FT-IR and DSC. Spectrophotometry was established for the determination of HP-beta-CD, based on the fact that the absorbance of phenolphthalein (PP) decreased in the presence of HP-beta-CD.
Methods: The assay conditions were optimized to augment the method sensitivity. Molecular docking was employed to verify the strong interaction between PP and HP-beta-CD. The permeation process of free HP-beta-CD, HP-beta-CD of OL inclusion complex, free OL, and OL in the inclusion complex,
was examined using an in vitro mouse small intestine model. Results: Though HP-beta-CD possessed a hydrophilic outside shell, it could permeate through the mouse small intestine quickly with a cumulative permeating amount of over 90% in 2 h. Free HPbeta- CD, the host molecule HP-beta-CD,
and guest molecule OL of the inclusion complex exhibited consistent permeating profiles across the mouse small intestine. Conclusion: The approach for the determination of HP-beta-CD was accurate and precise (%RSD=2.98).
研究领域:
药剂学
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生物药剂学
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药物分析
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DOI
高影响因子
Food Bioscience
·
2025
·
IF 5.9
Yongjie Zhou,Zixin Fu,Peipei Dou,Chen Yu,Xianyou Dong,Hui Hong,Yongkang Luo,Yuqing Tan
Nattokinase (NK), an alkaline serine protease, is recognized for its cardiovascular benefits through the modulation of blood coagulation and fibrinolytic pathways. Atherosclerosis (AS), a primary cause of cardiovascular disease (CVD) worldwide, is responsive to dietary interventions. However, studies investigating NK’s digestion, absorption, and mechanisms in mitigating AS remain limited. This study evaluated the effects of high-dose NK treatment (H-NK, 900 FU/kg body weight) administered over six weeks in ApoE -/- mice, which resulted in significant reductions in atherosclerotic lesions. In vitro digestion simulations showed that 25.8% of NK’s enzymatic activity was retained post-digestion, and thrombolysis assays demonstrated a thrombolytic efficacy of 30%-40% at concentrations ≥ 5,000 μg/mL, regardless of clot age. Absorption experiments using a rat everted intestinal sac model revealed a small intestine absorption rate of 37.0%, with the absorbed peptides being predominantly hydrophobic, uncharged, and shorter than 10 amino acids. Proteomic analysis of mouse liver tissues identified that high-dose NK down-regulated PXDN (peroxidasin) and PNLIP (pancreatic lipase), proteins involved in promoting lipid oxidation, and intestinal lipid absorption. These proteomic changes enhanced lipid metabolism, reduced lipid peroxidation, and alleviated AS through the "Lipid and Atherosclerosis" pathway. Overall, this study provides a deeper understanding of NK’s biological activity and supports its potential as a novel dietary supplement for the management of CVD.
研究领域:
心血管疾病研究
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营养学
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分子生物学
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产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2024
·
IF 5.3
Yehan Li,Fei Liu,Jiajing Che,Yu Zhang,Tian Yin,Jingxin Gou,Xing Tang,Yanjiao Wang,Haibing He
The aim of this study was to prepare sodium glycocholate liposomes (SGC-Lip) encapsulating semaglutide (Sml) to improve oral bioavailability and better exert hypoglycemic effect. In this paper, SGC-Lip was prepared by reverse-phase evaporation method with particle size around 140 nm, potential around -27 mV, rounded morphology and better stability. The hypoglycemic and intestinal uptake effects of SGC-Lip and cholesterol-containing liposomes (CH-Lip) were comparatively investigated in rats, and the oral safety of SGC-Lip was examined by cytotoxicity assay. The results indicate that SGC-Lip can achieve a hypoglycemic effect of 40% of the initial value within 12 hours, and the AAC 0-12h is approximately six times that of CH-Lip without sodium glycocholate. The results of the cytotoxicity tests indicate that SGC-Lip has good oral safety. SGC-Lip enhances the absorption of semaglutide in the small intestinal villi via an apical sodium-dependent bile acid transporter (ASBT)-mediated pathway with the highest penetration at the ileal site. In summary, the oral bioavailability of semaglutide can be improved by encapsulating semaglutide in SGC-Lip and utilizing the stabilizing and permeation-promoting effects of SGC on liposomes.
研究领域:
药剂学
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药物递送系统
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代谢病学
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产品关联
DOI
PubMed
高影响因子
Evidence-based Complementary and Alternative Medicine
·
2018
·
IF 2.064
Renjie Xu,Yichu Yuan,Jia Qi,Jia Zhou,Xiaowen Guo,Jian Zhang,Ruanjuan Zhan
Loganin, iridoid glycosides, is the main bioactive ingredients in the plant Strychnos nux-vomica L. and demonstrates various pharmacological effects, though poor oral bioavailability in rats. In this study, the intestinal absorption mechanism of loganin was investigated using the human intestinal Caco-2 cell monolayer model in both the apical-to-basolateral (A-B) and the basolateral-to-apical (B-A) direction; additionally, transport characteristics were systematically investigated at different concentrations, pHs, temperatures, and potential transporters. The absorption permeability (AB) of loganin, which ranged from 12.17 to 14.78 × 10−6cm/s, was high at four tested concentrations (5, 20, 40, and 80μM), while the major permeation mechanism of loganin was found to be passive diffusion with active efflux mediated by multidrug resistance-associated protein (MRP) and breast cancer resistance protein (BCRP). In addition, it was found that loganin was not the substrate of efflux transporter P-glycoprotein (P-gp) since the selective inhibitor (verapamil) of the efflux transporter exhibited little effects on the transport of loganin in the human intestinal Caco-2 cells. Meanwhile, transport from the apical to the basolateral side increased 2.09-fold after addition of a MRP inhibitor and 2.32-fold after addition of a BCRP inhibitor. In summary, our results clearly demonstrate, for the first time, a good permeability of loganin in the human intestinal Caco-2 cell model and elucidate, in detail, the intestinal absorption mechanism and the effects of transporters on iridoid glycosides compounds.
研究领域:
药理学
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生物医学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Xiaochun Wu,Yan Xu,Dandan Zhu,Weiye Zhang,Yanjun Yang,Liang Feng,Bing Yang,Xiaobin Jia
Understanding the absorption of natural polysaccharides is crucial for advancing their development and application. However, their oral absorption mechanisms and potential applications remain unclear. In this study, Astragalus homogeneous polysaccharide (APS3a) was isolated and characterized. Based on the structural analysis, in vitro and in vivo tracking of APS3a was conducted using FITC- and Cy7 amine labeling to investigate its transport and absorption mechanisms. The results indicated that APS3a can traverse the intestinal mucus layer and is mainly absorbed in the jejunum, subsequently distributing gradually to the liver and kidneys. Further investigation of its transport mechanism revealed that APS3a undergoes energy-dependent active transport, utilizing transcellular transport pathways such as caveolin-mediated endocytosis, macropinocytosis, and sodium-glucose cotransporter 1 (SGLT1)-mediated endocytosis. Additionally, APS3a has the capacity to reversibly open tight junction proteins, facilitating transport through the paracellular transport pathway. Moreover, APS3a can function as an excipient, self-assembling with flavonoids from Astragalus Radix to form complexes, thereby enhancing the permeability and absorption of these flavonoids. These findings provide valuable insights into the oral absorption of APS3a and its potential applications, which are significant for the development and application of polysaccharides.
研究领域:
药剂学
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分子药理学
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生物药剂学
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天然产物化学
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药物代谢
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肠道吸收
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纳米药物递送
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2024
·
IF 4.8
Yanjun Yang,Zhouyang Qian,Chenhui Wu,Yue Cheng,Bing Yang,Jianguo Shao,Jing Zhao,Xiangjun Zhu,Xiaobin Jia,Liang Feng
Ethnopharmacological relevance Pudilan Xiaoyan Oral Liquid (PDL) is a proprietary Chinese medicinal preparation approved by the State for treating acute pharyngitis in both adults and children (Approval No. Z20030095). It is worth noting that children exhibit unique physiopathological characteristics compared to adults. However, the in vivo regulatory characteristics of PDL in treating acute pharyngitis in children remain incompletely understood. Aim of the study The differential absorption and metabolism characteristics of the main pharmacological components in PDL in young and adult rats were investigated with a view to providing a reference for preclinical data of PDL in medication for children. Materials and Methods This study utilized UPLC-Q-TOF-MS to investigate the pharmacodynamic material basis of PDL. The focus was on the gastrointestinal digestion and absorption characteristics of organic acid components in PDL (PDL-OAC), known as the primary pharmacodynamic components in this formulation. The research combined in vitro dynamic simulation and a Quadruple single-pass intestinal perfusion model to examine these characteristics. The permeability properties of PDL-OAC were evaluated using an artificial parallel membrane model. Additionally, an acute pharyngitis model was established to evaluate the histopathological condition of the pharynx in young rats using H&E staining. The levels of IL-1 β , TNF- α , IL-6, and IL-10 in blood and pharyngeal tissue homogenates of young rats were quantified using ELISA kits. Results A total of 91 components were identified in PDL, including 33 organic acids, 24 flavonoids, 14 alkaloids, 5 terpenoids and coumarins, 3 sugars, and 12 amino acids. The PDL-OAC exhibited a significant reduction in IL-1 β , TNF- α , IL-6, and IL-10 levels in the pharyngeal tissues of young rats with acute pharyngitis. Results from dynamic simulation studies of gastrointestinal fluids revealed that the PDL-OAC (Specifically chlorogenic acid (CGA), gallic acid (GA), chicoric acid (CRA), and caffeic acid (CA)) were effectively stabilized in the gastrointestinal fluids of both children and adults in vitro . Young rats, characterized by thinner intestinal walls and higher permeability, efficiently absorbed the four organic acids across the entire intestinal segment. The absorption of CGA, GA, and CRA followed a concentration-dependent pattern, with CGA and GA absorption being influenced by exocytosis. Conclusion The efficacy of the PDL-OAC in treating acute pharyngitis was demonstrated in young rats. The absorption rate of these components was observed to be faster in young rats compared to adult rats, underscoring the need for dedicated studies on the drug's usage in children. This research provides valuable insights for the appropriate clinical use of PDL in pediatric patients.
研究领域:
药理学
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民族药理学
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儿科
·
药学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2018
·
IF 3.115
Min Zhang,Ying Peng,Mengyue Wang,Beibei Gao,Lijuan Zhao,Xiaobo Li
Ethnopharmacological relevance In traditional Chinese medicine , processed aconite root (lateral root of Aconitum carmichaelii Debx.) is used as the principle herb of the Si-Ni decoction (SND) formula due to its cardiotonic effect, while its cardiotoxicity and neurotoxicity caused by diester and monoester diterpenoid alkaloids are reduced by compatibility of dried ginger and honey-processed liquorice in SND. Aim of the study To investigate the detoxification of processed aconite root by compatibility of SND from the perspective of intestinal absorption with metabolism in intestinal bacteria . Materials and methods Decoctions of processed aconite root (AD), processed aconite root and honey-processed liquorice (ALD), and SND with the same amount of each herb were prepared, then were incubated in human intestinal bacteria juice (IBJ) in vitro for different durations. Bidirectional transmembrane transports of these decoctions and their IBJ-incubated decoctions were conducted on Caco-2 monolayers. Correlation between efflux ratios changes of benzoylmesaconine, benzoylaconine, benzoylhypaconine (monoester-diterpenoid alkaloids, MDAs) and hypaconitine (diester-diterpenoid alkaloids) from processed aconite root, and metabolic trends of compounds from honey-processed liquorice and dried ginger were also performed. Results The absorption of MDAs from processed aconite root was increased by combination with honey-processed liquorice in ALD, but they were decreased significantly by the addition of dried ginger in SND. Take benzoylhypaconine for example, the P app, AP to BL soared from ( 3.13 ± 0.18) × 10 −7 cm/s in AD to (23.32 ± 3.51) × 10 −7 cm/s in ALD, while it dropped to (1.12 ± 0.17) × 10 −7 cm/s in SND. When herb combined decoctions metabolised by intestinal bacteria for 12 h, the efflux ratio of benzoylhypaconine were both increased from 0.56 to 1.21 in ALD and from 1.10 to 2.61 in SND, which was correlative with the generation of davidigenin and glycyrrhetic acid (the metabolites of chalcones and pentacyclic triterpenoids from liquorice) in ALD and with the metabolism of [6]-gingerol (the major compound from dried ginger) in SND, respectively. Conclusions Compatibility of SND altered the intestinal absorption of toxic MDAs and hypaconitine from processed aconite root. In SND, dried ginger rather than honey-processed liquorice played the role of detoxification of these toxic compounds in the intestinal absorption. The intestinal detoxification of SND was significantly and strongly correlative with metabolism of dried ginger and honey-processed liquorice by intestinal bacteria, simultaneously.
研究领域:
药理学
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民族药理学
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微生物学
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毒理学
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中医药学
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产品关联
DOI
PubMed
高影响因子
Science Advances
·
2024
·Vol. 10
·期 35
·
IF 11.7
Shujun Feng,Yu Zhang,Chunyuan Hou,Yuta Liu,Yanfeng Gao,Yujun Song,Jun Luo
Despite the therapeutic benefits of insulin-pramlintide dual-hormone therapy in diabetes, its application potential has been limited due to a lack of efficient delivery routes. Here, we developed a temperature-responsive dual-hormone foam nanoengine (HormFoam) and combined it with a customized spraying device to further construct an in situ foam-generating system for improving the rectal bioavailability of dual-hormone therapy. To support rapid clinical translation, a continuous microfluidic preparation for HormFoam was proposed, including the power unit of perfluorocarbon nanodroplets and the pharmaceutical components Pluronic F127–functionalized liposomal insulin and pramlintide. We found that HormFoam could consistently generate foams to drive drugs forward after rectal administration, which enhanced intestinal distribution and mucosa absorption, leading to systemic codelivery of insulin-pramlintide. HormFoam reproduced the physiology of endocrine pancreas for glycemic control and induced body weight loss while reversing metabolic disorders in diabetic mice with good biosafety. Therefore, HormFoam represents a state-of-the-art dual-hormone regimen with the potential to address unmet needs in diabetes management.
研究领域:
药学
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生物医学工程
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糖尿病研究
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药物递送系统
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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）