International Journal of Nanomedicine
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2018
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IF 4.37
Jiao Liu,Jie Cao,Jianhua Cao,Shangcong Han,Yan Liang,Mingfeng Bai,Yong Sun
Introduction Nanoparticles are increasingly used as drug carriers for oral administration. The delivery of drug molecules is largely dependent on the interaction of nanocarriers and gastrointestinal (GI) mucus, a critical barrier that regulates drug absorption. It is therefore important to understand the effects of physical and chemical properties of nanocarriers on the interaction with GI mucus. Unfortunately, most of the nanoparticles are unable to be prepared with satisfactory structural monodispersity to comprehensively investigate the interaction. With controlled size, shape, and surface chemistry, copolymers are ideal candidates for such purpose. Materials and methods We synthesized a series of diblock copolymers via the atom transfer radical polymerization method and investigated the GI mucus permeability in vitro and in vivo. Results Our results indicated that uncharged and hydrophobic copolymers exhibited enhanced GI absorption. Conclusion These results provide insights into developing optimal nanocarriers for oral administration.
研究领域:
药学
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材料科学
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生物医学工程
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DOI
PubMed
高影响因子
PLoS Pathogens
·
2025
·Vol. 21
·期 1
·e1012787
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IF 4.9
Tingting Wang,Huaizhi Yang,Qiushuang Sheng,Ying Ding,Jian Zhang,Feng Chen,Jianfeng Wang,Lei Song,Xuming Deng
Hypervirulent Klebsiella pneumoniae (hvKP) poses an alarming threat in clinical settings and global public health owing to its high pathogenicity, epidemic success and rapid development of drug resistance, especially the emergence of carbapenem-resistant lineages (CR-hvKP). With the decline of the “last resort” antibiotic class and the decreasing efficacy of first-line antibiotics, innovative alternative therapeutics are urgently needed. Capsule, an essential virulence determinant, is a major cause of the enhanced pathogenicity of hvKP and represents an attractive drug target to prevent the devastating clinical outcomes caused by hvKP infection. Here, we identified isoferulic acid (IFA), a natural phenolic acid compound widely present in traditional herbal medicines, as a potent broad-spectrum K . pneumoniae capsule inhibitor that suppresses capsule polysaccharide synthesis by increasing the energy status of bacteria. In this way, IFA remarkably reduced capsule thickness and impaired hypercapsule-associated hypermucoviscosity phenotype (HMV), thereby significantly sensitizing hvKP to complement-mediated bacterial killing and accelerating host cell adhesion and phagocytosis. Consequently, IFA facilitated effective bacterial clearance and thus remarkably protected mice from lethal hvKP infection, as evidenced by limited bacterial dissemination and a significant improvement in survival rate. In conclusion, this work promotes the development of a capsule-targeted alternative therapeutic strategy for the use of the promising candidate IFA as an intervention to curb hvKP infection, particularly drug-resistant cases.
Hypervirulent Klebsiella pneumoniae (hvKP) is becoming an imminent threat to public health because of the constant emergence of drug resistance and its devastating clinical outcomes. Meanwhile, the both notorious phenotypes are integrated to create carbapenem-resistant and hypervirulent K . pneumoniae (CR-hvKP), which leads to a scarcity of effective treatments. Therefore, there is an increasing urgent need for new therapeutics other than antibiotics. The indispensable role of capsule in immune evasion and pathogenesis renders it a promising target for developing novel alternative strategies to combat hvKP infections. In this study, we identified the small natural compound isoferulic acid (IFA) as a potent broad-spectrum inhibitor of K . pneumoniae capsule. Hypercapsule-associated hypermucoviscosity (HMV), a characteristic phenotype that has been shown to play a distinct and critical role in the pathogenesis of hvKP, is significantly impaired by IFA. RNA-seq analysis revealed that IFA interferes with the biosynthesis of capsule polysaccharide through altering bacterial metabolism status. Consequently, IFA sensitizes hvKP to serum killing and impedes capsule- and HMV-mediated resistance to adherence and phagocytosis. In vivo, IFA treatment facilitates effective host clearance and thereby systemically protects mice against hvKP infection. Our research sheds light on the development of capsule-targeted drug and provides an effective lead compound that may contribute to the management of hvKP infections as an intervention.
研究领域:
微生物学
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传染病学
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药物开发
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PubMed
高影响因子
CHEMICAL RESEARCH IN CHINESE UNIVERSITIES
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2025
·Vol. 41
·期 2
·358-366
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IF 3
Dong Jiaxin,Su Rui,Wu Xiaokang,Dong Deming,Wang Yining,Huang Chenni,Qiu Tao,Gu Yu,Hua Xiuyi,Liang Dapeng
The study of the metabolic toxicity of perfluorooctanoic acid (PFOA) is of great importance in assessing its potential impact on aquatic organisms and the aquatic environment, and provides a fundamental scientific basis for environmental protection and sustainable development. In this study, an electrospray ionization (ESI) source capable of direct analysis of solution samples was combined with a high-resolution Orbitrap Fusion Tribrid mass spectrometer to investigate the metabolic perturbations induced by different concentrations of perfluorooctanoic acid (PFOA) and their correlations in skin mucus and liver tissue of tilapia. Seven common metabolites were found in mucus and liver, and nitrogen metabolism pathways were disturbed in all of them. The up-regulation of glutamate in mucus may reflect an increased demand for amino acids and energy, whereas the down-regulation of glutamate in the liver may lead to dysregulation of nitrogen metabolism, protein synthesis and amino acid metabolism. Enrichment analyses suggest a dysregulation of nitrogen metabolism pathways, which may lead to impaired maintenance of tissue function and dysregulated energy metabolism in tilapia.
研究领域:
环境科学
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毒理学
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代谢组学
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DOI
高影响因子
IMMUNOLOGY LETTERS
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2025
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IF 2.8
Rui Kong,Jun Bai,Qing Yao,Xiaoqing Xu
Allergic asthma is characterized by persistent chronic airway inflammation, leading to mucus hypersecretion and airway hyperresponsiveness. Dual-specificity phosphatase 14 (DUSP14), a member of the DUSP family, is a key regulator in various biological processes. However, the function of DUSP14 in allergic asthma remains to be elucidated. In this study, we aim to explore the function and mechanism of DUSP14 in asthma-related airway inflammation. In an ovalbumin (OVA) asthma mouse model, DUSP14 was found to be significantly diminished. DUSP14 overexpression relieved airway inflammation and attenuated airway mucus production. In vitro , overexpression of DUSP14 attenuated IL-13-induced cellular inflammation and mucus hypersecretion in bronchial epithelial cells (BEAS-2B). Afterwards, we used the co-immunoprecipitation assay to confirm that DUSP14 interacted with TAK1. DUSP14 overexpression restrained the activation of TAK1 and NF-κB signaling pathway in vitro and in vivo . Taken together, our findings clearly showed that DUSP14 could alleviate airway inflammation by inhibiting TAK1 activity and NF-κB signaling pathway, positioning the DUSP14-TAK1-NF-κB regulatory axis as a potential therapeutic target for allergic asthma.
研究领域:
免疫学
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呼吸病学
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分子生物学
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PubMed
高影响因子
ACS Nano
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2023
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IF 17.1
Yiyang Guo,Yubin Ma,Xin Chen,Min Li,Xuehu Ma,Gang Cheng,Changying Xue,Yi Y. Zuo,Bingbing Sun
The penetration behavior of nanoparticles in mucous depends on physicochemical properties of the nanoparticles and the mucus microenvironment, due to particle–mucin interactions and the presence of the mucin mesh space filtration effect. To date, it is still unclear how the surface properties of nanoparticles influence their mucus penetration behaviors in various physiological and pathophysiological conditions. In this study, we have prepared a comprehensive library of amine-, carboxyl-, and PEG-modified silica nanoparticles (SNPs) with controlled surface ligand densities. Using multiple particle tracking, we have studied the mechanism responsible for the mucus penetration behaviors of these SNPs. It was found that PEG- and amine-modified SNPs exhibited pH-independent immobilization under iso-density conditions, while carboxyl-modified SNPs exhibited enhanced movement only in weakly alkaline mucus. Biophysical characterizations demonstrated that amine- and carboxyl-modified SNPs were trapped in mucus due to electrostatic interactions and hydrogen bonding with mucin. In contrast, high-density PEGylated surface formed a brush conformation that shields particle–mucin interactions. We have further investigated the surface property-dependent mucus penetration behavior using a murine airway distribution model. This study provides insights for designing efficient transmucosal nanocarriers for prevention and treatment of pulmonary diseases.
研究领域:
生物医学工程
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药剂学
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DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
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2025
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IF 11.5
Wanting Dai,Xiaoxiao Song,Rui Wang,Weiwei He,Junyi Yin,Shaoping Nie
Selenium deficiency associated with a high risk of many diseases remains a global challenge. Owing to the narrow margin between “nutrition-toxicity” doses of selenium, it is imperative to achieve accurate selenium supplement. Nano‑selenium (SeNPs) is a novel form of selenium supplement with low toxicity, but it could be trapped and removed by intestinal mucus, thus limiting its oral delivery. The mucus penetration of SeNPs is highly associated with interactions between SeNPs and mucin (the structural component of mucus). In this study, we selected four polysaccharides with different functional groups and molecular weights, i.e. chitosan oligosaccharide (COS), chitosan (CS), chitosan quaternary ammonium salt (HACC), and carboxymethyl cellulose (CMC) as templates to modify SeNPs. Then we systematically explored the non-covalent interactions between polysaccharides stabilized nano-Se (PS-SeNPs) and mucin, determined and examined mucus penetration behavior and mechanism of different PS-SeNPs by coarse-grained molecular dynamics simulations, both in vitro and in vivo . It could be observed that penetration of PS-SeNPs depends on their distinct surface properties and mucus pH conditions. COS-SeNPs with short oligosaccharide chains accumulated and bridged with mucin, hindering its mucus penetration at pH 7.4. While HACC-SeNPs with NH 3 + and N + exhibited high binding affinity with mucin, inducing its mucus penetration. The negatively charged CMC-SeNPs diffused freely in mucus due to their electrostatic-repelled interaction and hydrophobic interaction with mucin. This study establishes a theoretical foundation for precise application of SeNPs in oral administration and offers valuable insights into the precise utilization of polysaccharides as tailored carriers of nanoparticles in mucus-covered tissues.
研究领域:
生物医学工程
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药剂学
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DOI
PubMed
高影响因子
MOLECULAR NUTRITION & FOOD RESEARCH
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2025
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IF 4.2
Yi Wang,Suqing Lan,Laiming Zhang,Yunxuan Li,Ziyang Deng,Xingqian Ye,Haibo Pan,Shiguo Chen
Scope: Polyphenols reportedly possess strong in vitro α-glucosidase inhibitory activity, even higher than acarbose, but their in vivo regulation on postprandial hyperglycemia is poor. So far this typical problem of polyphenols remains unsolved, greatly hindering their application as α-glucosidase inhibitors. Methods and results: Here, we identify the small intestinal mucus layer acts as a barrier to significantly reduce in vivo α-glucosidase inhibitory activity of epigallocatechin gallate, prodelphinidin B digallate (proDB DG), and proanthocyanidins from Chinese bayberry leaves. Multispectroscopy, rheology, solvent method, and molecular docking analysis showed that these pyrogallol-based polyphenols, especially proDB DG strongly interacted with small intestinal mucins through hydrogen bonding, hydrophobic interactions, and electrostatic interactions. These interactions block polyphenols from penetrating the mucus layer, resulting in their low binding rates with α-glucosidase in vivo. Besides, polyphenol-driven aggregation of the mucins enhanced the barrier function and reduced the permeability of the mucus layer, resulting in delayed digestion and absorption of carbohydrates. Conclusions: The mucus barrier weakens the inhibitory activity of pyrogallol-based polyphenols against α-glucosidase. Hence, overcoming the mucus barrier is a promising strategy to improve the regulation of pyrogallol-based polyphenols against postprandial hyperglycemia in vivo, which helps them to become novel α-glucosidase inhibitors in the clinic.
研究领域:
营养学
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生物化学
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药理学
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DOI
PubMed
高影响因子
Frontiers in Microbiology
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2024
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IF 4
Xiao Yao,Du Mijia,Deng Yang,Deng Qinglin,Wang Xin,Yang Yiwen,Zhang Binghuo,Zhang Yu-Qin
Harmful algal blooms (HABs) in natural waters are of escalating global concern due to their detrimental impact on environmental health. Emerging evidence indicates that algae-bacteria symbionts can affect HAB features, though much about this interplay remains largely unexplored. The current study isolated a new species of Mucilaginibacter (type strain JXJ CY 39T) from culture biomass of the bloom-causing Microcystis aeruginosa FACHB-905 (Maf) from Lake Dianchi, China. Strain JXJ CY 39T was an aerobic, Gram-stain-negative rod bacterium that grew at 5–38°C, pH 4.0–11.0, and 0–3.0% NaCl. Taxonomic evaluation proposed a new species, with Mucilaginibacter lacusdianchii sp. nov., as the species epithet. Experimental results revealed that strain JXJ CY 39T spurred the growth of Maf by supplying soluble phosphorus and nitrogen during cultivation, despite the unavailability of soluble phosphorus and nitrogen. Additionally, by producing the plant hormone indole-3-acetate, strain JXJ CY 39T possibly impacted Maf’s functionality. Results from co-culture experiments with other strains from Maf biomass showed possible effects of strain JXJ CY 39T on the relationship between Maf and other cohabiting bacteria, as well as microcystin toxin production characteristics. Although Maf could foster the growth of strain JXJ CY 39T by supplying organic carbon, the strain’s growth could be regulated via specific chemical compounds based on antibiotic assays. Community composition analysis disclosed that this Mucilaginibacter strain positively affected Maf’s growth and modified densities and types of bacteria linked to Maf. Overall, these results suggest that the interactions between important HAB-causing organisms and their attached bacteria are complex, dynamic, and may influence the growth characteristics of algae.
研究领域:
环境科学
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微生物学
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PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2017
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IF 3.649
Lei Wu,Min Liu,Wei Shan,Yi Cui,Zhirong Zhang,Yuan Huang
Lipid nanoparticles (LNs) are widely investigated for oral drug delivery , and for achieving significant advantages in colloidal stability, biocompatibility and scaled-up possibility. However, researchers face challenge of developing methods to improve the ability of LNs in overcoming multiple barriers (i.e., mucus and epithelium barrier) in gastrointestinal (GI) tract because of the contradictory requirement of nanoparticle (NP) surface properties in the two processes. Therefore, we designed novel LNs with adjustable surface properties by coating lipid core with hydrophobic substitutes grafting N-(2-hydroxypropyl) methacrylamide copolymer (pHPMA). In the present study, different substitutes (i.e., monocyclic, polycyclic, and linear segments) were grafted on pHPMA backbone. Screening studies demonstrated that type and grafting degree of substitutes both influenced hydrophilic-hydrophobic properties of NP surface and improved penetration through mucus. When a hydrophilic-hydrophobic balance was achieved, NPs showed elevated mucus permeability compared with bare LNs; this phenomenon subsequently contributed to higher cellular uptake. Moreover, β-sitosterol (SITO)-modified pHPMA-coated (grafting degree: 5%) LNs (5% SITO-LNs) exhibited the highest mucus permeability, transepithelial transport, and in situ absorption. Interestingly, even with the highest surface hydrophilicity, 5% SITO-LNs with Caco-2 cells did not show impaired membrane affinity, which was not observed in other groups. Further investigations of mechanism demonstrated that membrane affinity was significantly enhanced by β-SITO-mediated interaction with Niemann-Pick C1-like 1 (NPC1L1) protein on cell membranes. These results proved that hydrophobic substitutes play a critical role in altering hydrophilic-hydrophobic property of particle surface and improving penetration through multiple barriers. β-SITO-induced specific interaction can provide additional benefits to efficiency of oral delivery of LNs.
研究领域:
药剂学
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生物材料学
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DOI
PubMed
高影响因子
APPLIED SURFACE SCIENCE
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2024
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IF 6.3
Xiaolai Zhang,Luxing Wei,Xiaoyong Qiu,Tianbiao Wu,Yiming Zhao,Baohua Hu,Teng Yang,Haichao Fu,Shuai Chen,Jun Huang
Okra is an important vegetable that is rich in mucilage, which is a promising and environment friendly bio-lubricant due to its excellent physicochemical and lubrication properties. In this work, the adsorption behavior and lubrication mechanism of purified okra mucilage on model surfaces ( e.g., freshly-cleaved mica) were systematically investigated using nano-mechanical techniques such as surface force apparatus and atomic force microscopy. Experimental results indicate that thin layers of okra-mucilage coatings are built up within 120 min after injecting diluted mucilage solution between two mica surfaces. Moreover, the confined mucilage layers can serve as good bio-lubricants and exhibit anti-wear performance. Because of the varying film thickness and configuration of adsorbed mucilage films, the measured friction coefficient (μ) is lower on hydrophobic silane ( e.g., octadecyltrichlorosilane) modified mica (μ ∼ 0.07) than that on hydrophilic mica (μ ∼ 0.12). Additionally, it is demonstrated that the incorporation of okra mucilage into the polyacrylamide hydrogel network could further reduce the interfacial friction by one order of magnitude at high loads (friction coefficient μ < 0.01). This work provides fundamental insights into the adsorption and lubrication behavior and mechanisms of water-based bio-lubricants on solid substrate, which contributes to the developing of environment friendly bio-lubricants for various applications.
研究领域:
材料科学
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生物学
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DOI
高影响因子
Biomaterials Science
·
2020
·Vol. 8
·期 23
·6786-6797
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IF 6.183
Jing Zhao,Jian Su,Lu Qin,Xin Zhang,Shirui Mao
Liposomes are promising vectors for pulmonary drug delivery, and have been used in marketed inhalation products. Membrane fluidity is an important property of liposomes. However, the influence of liposome membrane fluidity on its interaction with pulmonary physiological barriers is still unclear and needs elucidation. Here, a series of PEGylated DPPC (1,2-dihexadecanoyl-rac-glycero-3-phosphocholine) liposomes with different membrane fluidity were prepared, and their interaction with different pulmonary physiological barriers, including the mucus permeation capacity, macrophage uptake, trachea distribution and retention behavior, was investigated. The liposomes exhibited sizes of around 100 nm, near-neutral surface charge, and the membrane fluidity increased with increasing cholesterol ratio. In vitro studies showed that the liposomes with lower membrane fluidity presented optimal mucus permeation efficiency, while those with higher membrane fluidity displayed lower macrophage uptake. An in vivo trachea distribution study revealed that liposomes with low or medium membrane fluidity exhibited enhanced trachea permeation. No significant difference in lung retention was found among these liposomes. In conclusion, the mucus permeation and macrophage phagocytosis behavior of liposomes could be well tuned by changing their membrane fluidity.
研究领域:
药剂学
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生物医学工程
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呼吸系统研究
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2025
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IF 5.2
Yiyao Li,Huixian Tian,Han Zeng,Yu Zhang,Tian Yin,Haibing He,Jingxin Gou,Xing Tang
Oral delivery of peptide and protein drugs (PDs) is hindered by the impermeable intestinal mucosa, which consists of both the mucus layer and the epithelium. Therefore, double-layer (mucus layer and epithelium) overcoming nanocarriers need to be designed to enhance the transporting efficiency of PDs. However, the requirements for surface properties to penetrate these two barriers are quite distinct. In this study, nanoparticles (NPs) with balanced mucus permeation and cellular uptake were developed by modulating surface properties to improve the endocytosis efficiency of exenatide (EXT). The EXT-loaded ovolecithin (Lipoid E 80)/dextran/bovine serum albumin (EDB) NPs, solidified by sodium trimetaphosphate (STMP), were prepared through double emulsification combined with interfacial crosslinking solidification. The EDB NPs were then coated with cationic polyelectrolyte chitosan (CS) shell to form CS-EDB NPs, which exhibited 83.50 ± 0.44 % of encapsulation efficiency (EE), a particle size of approximately 277.0 ± 3.96 nm, and a Zeta potential of −16.2 ± 0.71 mV. Compared to uncoated EDB NPs, CS-EDB NPs showed a 1.1-fold reduction in mucus penetration (P app ), as measured using the Transwell mucus-penetrating model. However, CS-EDB NPs demonstrated a 2.15-fold and 1.77-fold increase in cellular uptake and transepithelial transport efficiency across a Caco-2/E-12 co-culture model, respectively, primarily driven by energy-dependent endocytosis and partially mediated by macropinocytosis. Furthermore, CS-EDB NPs achieved 13.29 % of pharmacological bioavailability and effectively regulated blood glucose, serum lipid levels, and improved islet function upon long-term administration. In conclusion, the core–shell structured CS-EDB NPs successfully protected against the harsh gastrointestinal tract (GIT) environment, providing improved endocytosis efficiency by slightly compromising mucus penetration while significantly enhancing cellular uptake, offering a promising approach for the oral delivery of PDs.
研究领域:
药剂学
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生物医学工程
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DOI
PubMed
高影响因子
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