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Comparative study of mucoadhesive and mucus-penetrative nanoparticles based on phospholipid complex to overcome the mucus barrier for inhaled delivery of baicalein

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Acta Pharmaceutica Sinica B 2020年第8期10卷 1576-1585页

作者： Wujun Dong Jun Ye Junzhuo Zhou Weijue Wang Hongliang Wang Xu Zheng Yanfang Yang Xuejun Xia Yuling Liu State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia MedicaChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China Beijing Key Laboratory of Drug Delivery Technology and Novel Formulation Institute of Materia MedicaChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China State Key Laboratory of Nonlinear Mechanics Institute of MechanicsChinese Academy of SciencesBeijing 100190China

Efficient mucosal delivery remains a major challenge for the reason of the respiratory tract mucus act as a formidable barrier to nanocarriers by trapping and clearing foreign particulates. The surface property of nanoparticles determines their retention and penetration ability within the respiratory tract mucus. However, the interaction between nanoparticles and mucus, and how these interactions impact distribution has not been extensively investigated. In this study, polymeric nanoparticles loaded with a baicalein-phospholipid complex were modified with two kinds of polymers, mucoadhesive and mucus-penetrative polymer. Systematic investigations on the physicochemical property, mucus penetration, transepithelial transport, and tissue distribution were performed to evaluate the interaction of nanoparticles with the respiratory tract. Both nanoparticles had a similar particle size and good biocompatibility, exhibited a sustained-release profile, but showed a considerable difference in zeta potential. Interestingly, mucus-penetrative nanoparticles exhibited a higher diffusion rate in mucus, deeper penetration across the mucus layer, enhanced in vitro cellular uptake, increased drug distribution in airways, and superior local distribution and bioavailability as compared to mucoadhesive *** results indicate the potential of mucus-penetrative nanoparticles in design of a rational delivery system to improve the efficiency of inhaled therapy by promoting mucus penetration and increasing local distribution and bioavailability.

关键词： sustained mucus barrier

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Effects of irradiated Ergosan on the growth performance and mucus biological components of rainbow trout Oncorhynchus mykiss

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Chinese Journal of Oceanology and Limnology 2016年第1期34卷 13-18页

作者： Najmeh SHEIKHZADEH Fatemeh CHEHRARA Marzieh HEIDARIEH Katayoon NOFOUZI Behzad BARADARAN Department of Food Hygiene and Aquatic Animals Faculty of Veterinary Medicine University of Tabriz Tabriz Iran Nuclear Science and Technology Research Institute Karaj Iran Departments of Pathobiology Faculty of Veterinary Medicine University of Tabriz Tabriz Iran Immunology Research Center Tabriz University of Medical Sciences Tabriz Iran

Effects of irradiated and non-irradiated Ergosan extract(alginic acid) on rainbow trout growth performance and skin mucosal immunity were compared. Ergosan was irradiated at 30 kGy in a cobalt-60 irradiator. A total of 252 fish(128.03±9.4 g) were randomly divided into four equal groups,given the basal diet either unsupplemented with Ergosan(control group) or supplemented with crude Ergosan(5 g/kg),ethanol-extracted Ergosan(0.33 g/kg) or irradiated Ergosan(0.33 g/kg) according to this protocol: basal diet for 15 days,treatment diet for 15 days,basal diet for 10 days and treatment diet for 15 days. Highest growth performance was observed in fish fed irradiated Ergosan(Pmucus protein level,but improved alkaline phosphatase level and hemagglutination titer compared with the control(basal diet without Ergosan) on day 55 offeeding trial(Pmucus biological components significantly in comparison with the control group(basal diet without Ergosan).

关键词： gamma-irradiation Ergosan growth performance mucus immune system rainbow trout

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Ulcerative colitis as a polymicrobial infection characterized by sustained broken mucus barrier

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World Journal of Gastroenterology 2014年第28期20卷 9468-9475页

作者： Shui-Jiao Chen Xiao-Wei Liu Jian-Ping Liu Xi-Yan Yang Fang-Gen Lu Department of Gastroenterology 2nd Xiangya Hospital of Central South University

To reduce medication for patients with ulcerative colitis(UC),we need to establish the etiology of *** intestinal microbiota of patients with inflammatory bowel disease(IBD)has been shown to differ from that of healthy controls and abundant data indicate that it changes in both composition and *** intestinal bacterial overgrowth is significantly higher in IBD patients compared with *** have been investigated for their capacity to reduce the severity of *** luminal surfaces of the gastrointestinal tract are covered by a mucus *** normally acts as a barrier that does not allow bacteria to reach the epithelial cells and thus limits the direct contact between the host and the *** mucus layer in the colon comprises an inner layer that is firmly adherent to the intestinal mucosa,and an outer layer that can be washed off with minimal *** bacteria can dissolve the protective inner mucus *** in renewal and formation of the inner mucus layer allow bacteria to reach the epithelium and have implications for the causes of *** this review,important elements of UC pathology are thought to be the intestinal bacteria,gut mucus,and the mucosa-associated immune system.

关键词： Ulcerative colitis mucus Infection Bacteria Etiology

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Model for mucus transport in the airways due to air motion： Effect of slipperiness

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International Journal of Biomathematics 2016年第5期9卷 171-183页

作者： Dipak Kumar Satpathi Kota Venkata Ratnamt Adepalli Ramu Department of Mathematics Birla Institute of Technology and Science Pilani Hyderabad Campus Jawahar Nagar Shameerpet Rangaveddy District 500078 India

In this paper, a circular three-layer flow model is proposed to study mucus transport in the airways due to air motion caused by mild forced expiration or mild coughing. mucus is represented by four-parameter viscoelastic fluid, a combination of Maxwell and Voigt elements, whereas air and serous fluid are taken as Newtonian fluids （incompressible）. The pressure gradient generated in the fluid layers is assumed to be given by a time- dependent function representing mild forced expiration or mild cough in the airways causing laminar flow. The effect of slip velocity at the mucus-serous interface caused by the presence of surfactant and at the top surface caused by immotile cilia are Mso taken into account. The roles of rheological properties of mucus on its transport are studied. The effect of serous fluid and its viscosity on mucus transport is also considered.

关键词： Viscoelastic Maxwell fluid mucus serous layer surfactant

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Fight them or feed them:how the intestinal mucus layer manages the gut microbiota

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Gastroenterology Report 2019年第1期7卷 3-12,I0001页

作者： Bjoern O.Schroeder Wallenberg Laboratory and Sahlgrenska Center for Cardiovascular and Metabolic Research Department of Molecular and Clinical MedicineInstitute of MedicineBruna Stra°ket 16University of GothenburgSE 41345 GothenburgSweden

The intestinal tract is inhabited by a tremendous number of microorganisms,termed the gut *** microorganisms live in a mutualistic relationship with their host and assist in the degradation of complex *** the gut microbiota is generally considered beneficial,the vast number of microbial cells also form a permanent threat to the ***,the intestinal epithelium is covered with a dense layer of mucus to prevent translocation of the gut microbiota into underlying *** mucus is an organized glycoprotein network with a host-specific glycan *** the mucus layer has long been considered a passive,host-designed barrier,recent studies showed that maturation and function of the mucus layer are strongly influenced by the gut *** return,the glycan repertoire of mucins can select for distinct mucosa-associated bacteria that are able to bind or degrade specific mucin glycans as a nutrient *** the intestinal mucus layer is at the crucial interface between host and microbes,its breakdown leads to gut bacterial encroachment that can eventually cause inflammation and ***,a dysfunctional mucus layer has been observed in colitis in mice and ***,the increased consumption of a low-fiber Western-style diet in our modern society has recently been demonstrated to cause bacteria-mediated defects of the intestinal mucus ***,I will review current knowledge on the interaction between gut bacteria and the intestinal mucus layer in health and *** the molecular details of this host–microbe interaction may contribute to the development of novel treatment options for diseases involving a dysfunctional mucus layer,such as ulcerative colitis.

关键词： Dietary fiber gut microbiota host-microbe interaction inflammatory bowel disease mucus mucin mucosal barrier metabolic disease probiotics ulcerative colitis

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Development of a physiologically relevant dripping analytical method using simulated nasal mucus for nasal spray formulation analysis

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Journal of Pharmaceutical Analysis 2016年第5期6卷 283-291页

作者： Tina Masiuk Parul Kadakia Zhenyu Wang Respiratory Product Development Merck Research Laboratories Merck & Co.Inc.

Current methods for nasal spray formulations have been elementary evaluating the dripping characteristics of a formulation and have not assessed the behavior of the nasal formulation in the presence of varying types of mucus depending on the indication or diseased state. This research investigated the effects of nasal mucus on the dripping behavior of nasal formulations and focused on developing an improved in vitro analytical test method that is more physiologically relevant in characterizing nasal formulation dripping behavior. Method development was performed using simulated nasal mucus preparations for both healthy and diseased states as coatings for the dripping experiment representing a wide range of viscosity. Factors evaluated during development of this in vitro test method included amount of mucus, application of mucus, drying times, and compatibility of the mucus on a C18 Thin Layer Chromatography(TLC) substrate. The dripping behavior of nasal formulations containing a range of 1%Avicel to 3.5% Avicel was assessed by actuating the nasal spray on a perpendicular TLC plate coated with either healthy or diseased simulated nasal mucus. After actuation of the nasal spray, the dripping of the formulation on the coated TLC plate was measured after the plate was repositioned vertically. The method that was developed generated reproducible results on the dripping behavior of nasal formulations and provided critical information about the compatibility of the formulation with the nasal mucus for different diseased states, aiding in nasal spray formulation development and physical characterization of the nasal spray.

关键词： Nasal spray Nasal spray dripping method Nasal mucus Nasal formulation dripping

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Modulating intestinal mucus barrier for nanoparticles penetration by surfactants

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Asian Journal of Pharmaceutical Sciences 2019年第5期14卷 543-551页

作者： Xin Zhang Wei Dong Hongbo Cheng Meixia Zhang Yongqiang Kou Jian Guan Qiaoyu Liu Mingyue Gao Xiuhua Wang ShiruiMao School of Pharmacy Shenyang Pharmaceutical UniversityShenyang110016China Laboratory of Metabolic Disease Research and Drug Development China Medical UniversityShenyang110122China

Improving peroral delivery efficiency is always a persistent goal for both small-molecule and macromolecular drug development. However,intestinal mucus barrier which greatly impedes drug-loaded nanoparticles penetration is commonly overlooked. Therefore,in this study,taking fluorescent labeled PLGA(poly(lactic-co-glycolic acid)) nanoparticles as a tool,the influence of anionic and nonionic surfactants on mucus penetration ability of nanoparticles and their mucus barrier regulating ability were studied. The movement of PLGA nanoparticles in mucus was tracked by multiple particles tracking method(MPT).Alteration of mucus properties by addition of surfactants was evaluated by rheology and morphology study. Rat intestinal villus penetration study was used to further evaluate penetration enhancement of nanoparticles. The effective diffusivities of the nanoparticles in surfactants pretreated mucus were increased by 2–3 times and the mucus barrier regulating capacity was also surfactant type dependent. Sodium dodecyl sulfate(SDS) increased the complex viscosity and viscoelastic properties of mucus,but poloxamer presented a decreased trend. Tween 80 maintained the rheological property of the mucus. With the mucus barrier regulated by surfactants,the penetration of nanoparticles in intestinal villus was obviously increased. In summary,the mucus penetration ability of nanoparticles could be enhanced by altering mucus microenvironment with surfactants. Tween 80 which largely retains the original mucus rheology and morphology properties may be a promising candidate for facilitating nanoparticle penetration through the mucus barrier with good safety profile.

关键词： mucus barrier mucus modulating agents Rheology PLGA nanoparticles Surfactants

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The co-effect of microstructures and mucus on the adhesion of abalone from a mechanical perspective

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Biosurface and Biotribology 2021年第4期7卷 180-186页

作者： Jing Li Chuandong Ma Jun Liu Xiangwei Dong Jianlin Liu College of Mechanical and Electrical Engineering China University of Petroleum(East China)QingdaoChina College of Pipeline and Civil Engineering China University of Petroleum(East China)QingdaoChina

Reliable and reversible adhesion underwater is challenging due to the water molecules and weak layers of contaminants at the contact interface,which requires to deepen the un-derstanding of wet adhesion of biological ***,the co-effect of microstruc-tures and mucus of abalone foot on wet adhesion is investigated from both experimental and theoretical *** morphologies,adhesion force and coefficient of friction indicate that the mucus in adhesion zone is crucial for successful attachment of abalone based on capillary forces and viscous forces,and the mucus in non-adhesion zone with lower adhesion force and friction coefficient may behave as a lubricant for the *** theoretical calculation manifests that the microstructures may help abalone to form multiple liquid bridges with the secreted mucus,and significantly increase the wet adhesion force of *** findings will bring profound views into the underlying mechanisms of biological surface adhesion.

关键词： abalone capillary force microstructure mucus wet adhesion

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Antimicrobial and hemolytic activity of fish epidermal mucus Cynoglossus arel and Arius caelatus

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Asian Pacific Journal of Tropical Medicine 2011年第4期4卷 305-309页

作者： Subramanian Bragadeeswaran Selvam Priyadharshini Kolandhasamy Prabhu Solomon Raj Sophia Rani Centre of Advanced Study in Marine Biology Faculty of Marine SciencesAnnamalai University

Objective:To study the antimicrobial,hemolytic activity and immunomodulatory activity of fish epidermal mucus and their chemical constituents from Cynoglossus arel(***) and Alius caelatus(***).mucus plays an important role in the prevention of colonization by parasites,bacteria and ***:Epidermal mucus was obtained from two marine fishes,lyophilized and the chemical composition of epidermal mucus was analysed by FT-IR *** in vitro antimicrobial activity against human pathogens(fungi,gram positive and gram-negative bacteria) and also the hemolytic activity and immunomodulatory activity were ***:Totally ten human pathogens were tested against the fish *** of the ten pathogens,five pathogens have proved to be sensitive to the *** zone of inhibition was observed against Vibrio cholera(***)(9 mm and 2 mm in diameter),followed by Staphylococcus aureus(***) with a inhibition zone of(6 mm and 3 mm),Streptococcus areus(***)(5 mm and 4 mm),Vibrio parahemolyticus(***)(4 mm and 5 mm) ***:The present investigation has revealed that positive progresses in the fish mucus extracts against human pathogens and hemolytic *** further efforts are required for the purification and isolation of the active antimicrobial compounds in order to establish their possible applications.

关键词： Antibacterial activity Antifungal activity Fish mucus Cynoglossus arel Arius caelatus

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Bicarbonate Effects on Antibacterial Immunity and mucus Glycobiology in the Cystic Fibrosis Lung:A Review With Selected Experimental Observations

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Infectious Microbes & Diseases 2022年第3期4卷 103-110页

作者： Ruth Siew Tzung-Lin Ou Samira Dahesh Kathryn Akong Victor Nizet Department of Pediatrics University of California San DiegoLa JollaCaliforniaUSA School of Medicine China Medical UniversityTaichungTaiwan Skaggs School of Pharmacy and Pharmaceutical Sciences University of California San DiegoLa JollaCaliforniaUSA

The primary defect in cystic fibrosis(CF)is abnormal chloride and bicarbonate transport in the CF transmembrane conductance regulator epithelial ion *** apical surface of the respiratory tract is lined by an airway surface liquid(ASL)layer composed of mucin comprising mainly MUC5A and MUC5B *** homeostasis depends on sodium bicarbonate secretion into the airways and secretion deficits alter mucus properties leading to airway obstruction,inflammation and *** effects of abnormal ion transport in the lungs include altered intrinsic immune *** observed that neutrophils killed Pseudomonas aeruginosa more efficiently when it had been exposed to sodium bicarbonate,and formation of neutrophil extracellular traps by neutrophils was augmented in the presence of increasing bicarbonate *** levels of bicarbonate sensitized *** to the antimicrobial peptide cathelicidin LL-37,which is present in both lung ASL and neutrophil extracellular *** bicarbonate has various uses in clinical medicine and in the care of CF patients and could be further explored as a therapeutic adjunct against Pseudomonas infections.

关键词： cystic fibrosis bicarbonate mucus pneumonia bacterial infection neutrophil cathelicidin neutrophil extracellular traps

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