Oxidized cholesterol(OXC)is a harmful dietary substance.Although the consumption of OXC has been associated with colonic inflammation,related underlying mechanisms are still limited.We evaluated the influence of dieta...Oxidized cholesterol(OXC)is a harmful dietary substance.Although the consumption of OXC has been associated with colonic inflammation,related underlying mechanisms are still limited.We evaluated the influence of dietary OXC on gut health and ecology by applying the murine model.Results showed that the thickness of the mucus layer was significantly reduced in healthy mice treated with OXC.Short-term intake of OXC did not influence the expression of pro-inflammatory factors in healthy mice but it induced the decrease of Muc2 expression in the proximal colon,accompanied by an increase in the abundance of 2 mucusdegrading bacteria,namely Akkermansia muciniphila and Bacteroides acidifaciens.Consistently,oral exposure of OXC promoted mucus barrier erosion in dextran sulfate sodium(DSS)-induced colitis mice and facilitated bacteria infiltration in the colon.The adverse effect of OXC on mucus layer disappeared in antibiotics-treated healthy mice,suggesting that the damaging effect of OXC on the gut mucus layer was not direct and instead was mediated by causing microbiota dysbiosis.Finally,the impact of OXC on the mucus layer and colitis was partly alleviated by green tea catechins.These studies demonstrated that the OXC-induced mucus barrier damage was mainly induced by the dysregulation of gut microbiota at least in this mouse model.展开更多
Dry powder inhalation represents a promising approach for the treatment of lung cancer,offering several advantages such as enhanced targeting,improved bioavailability,and reduced toxicity.However,traditional dry powde...Dry powder inhalation represents a promising approach for the treatment of lung cancer,offering several advantages such as enhanced targeting,improved bioavailability,and reduced toxicity.However,traditional dry powder formulations suffer from limitations,notably low pulmonary delivery efficiency and inadequate penetration into tumor tissues,thereby limiting their therapeutic efficacy.In response to these challenges,we have developed an innovative trojan horse strategy,harnessing an inhalable nanoparticlein-microsphere system characterized by tunable size,reversible charge,and mucus-penetrating capabilities.The inhalable nanoparticle-in-microsphere system exhibit stable structural properties,excellent environmental responsiveness and high biocompatibility.More importantly,the therapeutic effect of MTX@PAMAM@HA@Gel(MPHG)was demonstrated in vitro and in vivo.This system offers improved pulmonary delivery efficiency,enhanced drug retention within tumor tissues,and effective penetration,thus representing a promising strategy in lung cancer treatment.展开更多
Local delivery of nanoparticles holds promise for colorectal cancer(CRC)therapy.However,the presence of the mucus layer on the epithelium poses a significant challenge to drug delivery,thereby adversely affecting trea...Local delivery of nanoparticles holds promise for colorectal cancer(CRC)therapy.However,the presence of the mucus layer on the epithelium poses a significant challenge to drug delivery,thereby adversely affecting treatment efficiency.It is crucial to develop efficient drug delivery carriers that can effectively overcome mucus barriers to treat colorectal cancer.Herein,we utilized poly(1,4-butadiene)-b-poly(ethylene oxide)polymers to prepare four distinct geometries of polymeric micelles,namely linear micelles(LMs),worm-like micelles(WLMs),large spherical micelles(LSMs),and small spherical micelles(SSMs)to investigate the influence of shape effects on overcoming colonic mucosal barrier.We found that the carriers exhibited diverse shapes while maintaining comparable physicochemical properties.Of these,WLMs had an aspect ratio similar to segmented filamentous bacteria,which exhibited superior mucus penetration ability,leading to prolonged drug release kinetics and faster entry into epithelial cells compared to LSMs.Furthermore,rectally administrated 10-hydroxycamptothecin-loaded WLMs traversed the colorectal mucus in orthotopic CRC nude mice model,penetrated and accumulated within tumor tissue,and effectively aggregated within cancer cells,thereby inducing significantly robust antitumor outcomes in vivo.These findings underscore the significance of shape design in overcoming colonic mucosal absorption barriers,offering a novel approach for the development of drug delivery carriers tailored for effective tumor therapy.展开更多
Mucus can effectively protect the exposed mucosal surfaces due to its adhesive and viscoelastic properties.Most foreign particulates are efficiently trapped in mucus layers via steric obstruction and adhesion.Trapped ...Mucus can effectively protect the exposed mucosal surfaces due to its adhesive and viscoelastic properties.Most foreign particulates are efficiently trapped in mucus layers via steric obstruction and adhesion.Trapped particles are typically removed from the mucosal tissue within seconds to a few hours depending on their location sites.This article focuses on describing the tenacious mucus barrier properties,the strategies to investigate the interaction of nanoparticles with the mucus as well as the novel developments of mucus penetrating nanoparticles.展开更多
To reduce medication for patients with ulcerative colitis(UC),we need to establish the etiology of UC.The intestinal microbiota of patients with inflammatory bowel disease(IBD)has been shown to differ from that of hea...To reduce medication for patients with ulcerative colitis(UC),we need to establish the etiology of UC.The 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 localization.Small intestinal bacterial overgrowth is significantly higher in IBD patients compared with controls.Probiotics have been investigated for their capacity to reduce the severity of UC.The luminal surfaces of the gastrointestinal tract are covered by a mucus layer.This 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 bacteria.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 rinsing.Some bacteria can dissolve the protective inner mucus layer.Defects in renewal and formation of the inner mucus layer allow bacteria to reach the epithelium and have implications for the causes of colitis.In this review,important elements of UC pathology are thought to be the intestinal bacteria,gut mucus,and the mucosa-associated immune system.展开更多
AIM:To assess the mucosa-associated bacterial microflora and mucus layer in adolescents with inflammatory bowel disease(IBD) .METHODS:Sixty-one adolescents(mean age 15 years,SD ± 4.13) were included in the study....AIM:To assess the mucosa-associated bacterial microflora and mucus layer in adolescents with inflammatory bowel disease(IBD) .METHODS:Sixty-one adolescents(mean age 15 years,SD ± 4.13) were included in the study.Intestinal biopsies from inflamed and non-inflamed mucosa of IBD patients and from controls with functional abdominal pain were cultured under aerobic and anaerobic conditions.The number of microbes belonging to the same group was calculated per weight of collected tissue.The mucus thickness in frozen samples was measured under a fluorescent microscope.RESULTS:The ratios of different bacterial groups in inflamed and non-inflamed mucosa of IBD patients and controls were specific for particular diseases.Streptococcus spp.were predominant in the inflamed mucosa of Crohn's disease(CD) patients(80% of all bacteria) ,and Lactobacillus spp.were predominant in ulcerative colitis patients(90%) .The differences were statistically significant(P = 0.01-0.001) .Lower number of bifidobacteria was observed in the whole IBD group.A relation was also found between clinical and endoscopic severity and decreased numbers of Lactobacillus and,to a lesser extent,of Streptococcus in biopsies from CD patients.The mucus layer in the inflamed sites was significantly thinner as compared to controls(P = 0.0033) and to non-inflamed areas in IBD patients(P = 0.031) .CONCLUSION:The significantly thinner mucosa of IBD patients showed a predominance of some aerobes specific for particular diseases,their numbers decreased in relation to higher clinical and endoscopic activity of the disease.展开更多
Objective:To study the antimicrobial,hemolytic activity and immunomodulatory activity of fish epidermal mucus and their chemical constituents from Cynoglossus arel(C.arel) and Alius caelatus(A.caelatus).Mucus plays an...Objective:To study the antimicrobial,hemolytic activity and immunomodulatory activity of fish epidermal mucus and their chemical constituents from Cynoglossus arel(C.arel) and Alius caelatus(A.caelatus).Mucus plays an important role in the prevention of colonization by parasites,bacteria and fungi.Methods:Epidermal mucus was obtained from two marine fishes,lyophilized and the chemical composition of epidermal mucus was analysed by FT-IR analysis.The in vitro antimicrobial activity against human pathogens(fungi,gram positive and gram-negative bacteria) and also the hemolytic activity and immunomodulatory activity were determined.Results:Totally ten human pathogens were tested against the fish mucus.Out of the ten pathogens,five pathogens have proved to be sensitive to the mucus.Maximum zone of inhibition was observed against Vibrio cholera(V.cholera)(9 mm and 2 mm in diameter),followed by Staphylococcus aureus(S.aureus) with a inhibition zone of(6 mm and 3 mm),Streptococcus areus(S.areus)(5 mm and 4 mm),Vibrio parahemolyticus(V.parahemolyticus)(4 mm and 5 mm) respectively.Conclusions:The present investigation has revealed that positive progresses in the fish mucus extracts against human pathogens and hemolytic activity.But further efforts are required for the purification and isolation of the active antimicrobial compounds in order to establish their possible applications.展开更多
Adhesion of Vibrio alginolyticus to the gill mucus of Pseudosciaena crocea has been investigated using [ methyl-^3 H ] thymidine as isotope tracer. The results showed that： the adhesive quantity of V. alginolyticus i...Adhesion of Vibrio alginolyticus to the gill mucus of Pseudosciaena crocea has been investigated using [ methyl-^3 H ] thymidine as isotope tracer. The results showed that： the adhesive quantity of V. alginolyticus increased with bacterial concentrations and reached equilibrium after incubated for 180 min; the higher adhesive quantity was obtained at 15 ~ 30 ℃ and sourish conditions; adhesion of V. alginolyticus could not achieved without Na^＋ , and Ca^2＋ played an auxiliary role in the bacterial adhesion; adhesion of V. alginolyticus was inhibited remarkably by starvation, heat treatment and periodic acid treatment; all of the eight kinds of carbohydrates investigated enhanced the adhesion of V. alginolyticus to the gill mucus of P. crocea, among them, glucose, mannose, fructose and maltose showed the specially enhanced adhesion. The results indicated that E alginolyticus could adhere to the gill mucus of P. crocea facilely in seawater, and this bacterial adhesion was influenced by environmental factors and closely related to superficial carbohydrate structures and some heat-sensitive structures.展开更多
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 penetrati...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.展开更多
Self-nanoemulsifying systems(SNEs) have excellent ability to improve the solubility ofpoorly water-soluble drugs(PWSD). However, SNEs are likely to be degraded in gastroin-testinal(GIT) when their surface is recognize...Self-nanoemulsifying systems(SNEs) have excellent ability to improve the solubility ofpoorly water-soluble drugs(PWSD). However, SNEs are likely to be degraded in gastroin-testinal(GIT) when their surface is recognized by lipase/co-lipase enzyme complex, result-ing in rapid release and precipitation of encapsulated drugs. The precipitates are then cap-tured and removed by intestinal mucus, reducing the delivery efficacy of SNEs. Herein, theamphiphilic polymer Pluronic? F127 was incorporated into long and short-chain triglyc-erides(LCT, SCT) based SNEs to diminish the recognition and therefore minimized theirdegradation by enzymes and clearance by mucus. The SNEs were characterized in termsof particle size, zeta potential and stability. Ex vivo multiple particles tracking studies wereperformed by adding particle solution into fresh rat mucus. Cellular uptake of SNEs wereconducted by using E12 cells, the absorption and distribution in small intestine were alsostudied after oral administration in male Sprague-Dawley(SD) rats. The in vitro digestionrate of SNEs were found to be in following order SCT-SNE > SCT-F127-SNE > LCT-SNE > LCT-F127-SNE. Moreover, the LCT-F127-SNE was found to be most effective in enhancing cellularuptake, resulting in 3.5-fold, 2.1-fold and 1.7-fold higher than that of SCT-SNE, LCT-SNE andSCT-F127-SNE, respectively. After incubating the SNE with E12 cells, the LCT-F127-SNE ex-hibited the highest amount regarding both mucus penetration and cellular uptake, with anuptake amount number(via bicinchoninic acid(BCA) analysis) of 3.5-fold, 2.1-fold and 1.7-fold higher than that of SCT-SNE, LCT-SNE and SCT-F127-SNE, respectively. The in vivo results revealed that orally administered LCT-F127-SNE could significantly increase the bioavailability of Cyclosporine A(CsA), which was approximately 2.43-fold, 1.33-fold and 1.80-fold higher than that of SCT-SNE, SCT-F127-SNE and LCT-SNE, respectively. We address in this work that F127-modified SNEs have potentials to improve oral drug absorption by significantly reducing gastrointestinal enzymatic degradation and simultaneously enhancing mucus penetration.展开更多
Vibriofluvialis incubated in trypticase soy broth （TSB） showed stronger adhesion to the skin mucus of Epinephelus awoara than V. fluvialis grown on trypticase soy agar （TSA）, and this bacterial adhesion was assess...Vibriofluvialis incubated in trypticase soy broth （TSB） showed stronger adhesion to the skin mucus of Epinephelus awoara than V. fluvialis grown on trypticase soy agar （TSA）, and this bacterial adhesion was assessed in terms of saturation kinetics. Treating bacteria with antibody against O-antigens resulted in significantly reduced bacterial adhesion. In the early growth stage, the adhering bacteria numbers increased with incubation time, peaked at 24 h, and then dropped sharply. Prior heat treatment of the mucus at various temperatures resulted in different effects on bacterial adhesion. No remarkable effect on bacterial adhesion was detected after treating mucus with protease K and trypsin, whereas periodic acid treatment significantly enhanced bacterial adhesion. Extracts of K fluvialis surface structures at high concentrations significantly inhibited bacterial adhesion, while relatively low concentrations enhanced adhesion. V. fluvialis had strong affinity for a high molecular weight mucus component. These results indicate that V.fluvialis adhered strongly to E. awoara mucus by specific adhesion and that this adhesion was influenced by many factors, including bacterial conditions, mucus, and the environment.展开更多
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 o...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.展开更多
Objective Mucus forms the physical barrier along the gastrointestinal(GI)tract.It plays an important role to prevent mucosal damage and inflammation.Our previous finding showed that antibacterial peptide 'cathelic...Objective Mucus forms the physical barrier along the gastrointestinal(GI)tract.It plays an important role to prevent mucosal damage and inflammation.Our previous finding showed that antibacterial peptide 'cathelicidin' increased mucus thickness and prevented inflammation in the colon.In the current study,we examined the protective mechanisms by which the peptide increased mucus synthesis in vitro.Methods Human colonic cell line(HT-29)was used to assess the stimulatory action of cathelicidin on mucus synthesis which was measured by the D-[6-3H] glucosamine incorporation assay.Results Human cathelicidin(LL-37)dose-dependently(10-40 μg·mL-1)and significantly stimulated mucus synthesis.Real-time PCR data showed that addition of LL-37 induced more than 50% increase in MUC1 and MUC2 mRNA levels.Treatment with MUC1 and MUC2 siRNAs normalized the stimulatory action of LL-37 on mucus synthesis.LL-37 also activated the phosphorylation of mitogen-activated protein(MAP)kinase in the cells.A specific inhibitor of the MAP kinase pathway,U0126,completely blocked the increase of MUC1 and MUC2 expression as well as mucus synthesis by LL-37.Conclusions Taken together LL-37 stimulates mucus synthesis through the activation of MUC1 and MUC2 expression and the MAP kinase pathway in human colonic cells.展开更多
The aim of this study was to investigate whether a relationship exists between the presence of low numbers of leukocytes in normal ovulatory cervical mucus and sperm quality and lipid content after migration. The perc...The aim of this study was to investigate whether a relationship exists between the presence of low numbers of leukocytes in normal ovulatory cervical mucus and sperm quality and lipid content after migration. The percentages of live, motile and morphologically normal spermatozoa, movement parameters assessed by computer-aided sperm analysis （CASA）, and ionophore-induced acrosome reaction measured by flow cytometry were determined before and after migration. High-performance liquid chromatography with ultraviolet detection was used to measure the sperm lipid content, including the various diacyl subspecies. The number of leukocytes found in solubilized mucus samples was counted using a haemocytometric method. Overall, the presence of leukocytes in the cervical mucus samples did not significantly influence sperm motility and morphology, sperm kinematic parameters, or the sperm content in sphingomyelin or cholesterol. In contrast, after migration, the decrease in various sperm diacyls and the level of induced acrosome reaction was significantly less pronounced in mucus samples containing ≥10^4 leukocytes than in mucus samples with no or rare leukocytes whereas the level of induced acrosome reaction was higher. The present data suggest that the low level of leukocytes found in normal ovulatory cervical mucus could influence the process of sperm lipid remodelling/capacitation.展开更多
Loach skin mucin was isolated from loach skin mucus and found to be similar to mammalian mucins in many aspects, i.e., low amino acid residue content, high molecular weight, presence of hydrophobic blocks and gel-form...Loach skin mucin was isolated from loach skin mucus and found to be similar to mammalian mucins in many aspects, i.e., low amino acid residue content, high molecular weight, presence of hydrophobic blocks and gel-forming characteristics in water. However, loach skin mucin can form a weak gel in water at a much lower concentration （3 mg/mL） than mammalian mucins, indicating its good hydrophilicity. Loach skin mucin can also form a stable adsorption layer on gold surface in aqueous environment, owing to the existence of hydrophobic blocks within mucin. The nature of high hydrophilicity and interfacial behavior give loach skin mucin potential as excellent material for use in solid-water interfaces for antifouling and lubrication, and should be crucial to the versatile functions of loach skin mucus.展开更多
Little was known about mammalian colon mucus(CM)until the beginning of the 21^(st) century.Since that time considerable progress has been made in basic research addressing CM structure and functions.Human CM is formed...Little was known about mammalian colon mucus(CM)until the beginning of the 21^(st) century.Since that time considerable progress has been made in basic research addressing CM structure and functions.Human CM is formed by two distinct layers composed of gel-forming glycosylated mucins that are permanently secreted by goblet cells of the colonic epithelium.The inner layer is dense and impenetrable for bacteria,whereas the loose outer layer provides a habitat for abundant commensal microbiota.Mucus barrier integrity is essential for preventing bacterial contact with the mucosal epithelium and maintaining homeostasis in the gut,but it can be impaired by a variety of factors,including CM-damaging switch of commensal bacteria to mucin glycan consumption due to dietary fiber deficiency.It is proven that impairments in CM structure and function can lead to colonic barrier deterioration that opens direct bacterial access to the epithelium.Bacteria-induced damage dysregulates epithelial proliferation and causes mucosal inflammatory responses that may expand to the loosened CM and eventually result in severe disorders,including colitis and neoplastic growth.Recently described formation of bacterial biofilms within the inner CM layer was shown to be associated with both inflammation and cancer.Although obvious gaps in our knowledge of human CM remain,its importance for the pathogenesis of major colorectal diseases,comprising inflammatory bowel disease and colorectal cancer,is already recognized.Continuing progress in CM exploration is likely to result in the development of a range of new useful clinical applications addressing colorectal disease diagnosis,prevention and therapy.展开更多
Colonoscopy is currently the gold standard for diagnosis of inflammatory bowel disease(IBD)and colorectal cancer(CRC).This has the obvious drawback of being invasive as well as carrying a small risk.The most widely us...Colonoscopy is currently the gold standard for diagnosis of inflammatory bowel disease(IBD)and colorectal cancer(CRC).This has the obvious drawback of being invasive as well as carrying a small risk.The most widely used non-invasive approaches include the use of faecal calprotectin in the case of IBD and fecal immunochemical test in the case of CRC.However,the necessity of stool collection limits their acceptability for some patients.Over the recent years,there has been emerging data looking at the role of non-invasively obtained colorectal mucus as a screening and diagnostic tool in IBD and CRC.It has been shown that the mucus rich material obtained by self-sampling of anal surface following defecation,can be used to measure various biomarkers that can aid in diagnosis of these conditions.展开更多
Coral mucus covers the surface of coral and contains antibacterial substances as a first line of defense. Coral mucus not only enables the coral itself to resist disease, but also provides antibacterial agents for peo...Coral mucus covers the surface of coral and contains antibacterial substances as a first line of defense. Coral mucus not only enables the coral itself to resist disease, but also provides antibacterial agents for people. We collected mucus from a scleractinian coral （Symphyllia gigantea） at Sta. Sanya （China）, then extracted the antibacterial substances using 10% glacial acetic acid with the help of antiprotease inhibitors, and tested the antibacterial activity by a terrestrial bacterium （Staphylococcus aurevs） and a marine bacterium （Vibrio anguillarum）. The result showed that, there were antibacterial agents in the mucus, and their antibacterial activities were lost by treatment of the sample at 90 ℃ water for 10 min.展开更多
AIM To determine the ability of intrapulmonary percussive ventilation(IPV) to promote airway clearance in spontaneously breathing patients and those on mechanical ventilation.METHODS An artificial lung was used to sim...AIM To determine the ability of intrapulmonary percussive ventilation(IPV) to promote airway clearance in spontaneously breathing patients and those on mechanical ventilation.METHODS An artificial lung was used to simulate a spontaneously breathing patient(Group 1), and was then connected to a mechanical ventilator to simulate a patient on mechanical ventilation(Group 2). An 8.5 mm endotracheal tube(ETT) connected to the test lung, simulated the patient airway. Artificial mucus was instilled into the mid-portion of the ETT. A filter was attached at both ends of the ETT to collect the mucus displaced proximally(mouth-piece filter) and distally(lung filter). The IPV machine was attached to the proximal end of the ETT and was applied for 10-min each to Group 1 and 2. After each experiment, the weight of the various circuit components were determined and compared to their dry weights to calculate the weight of the displaced mucus.RESULTS In Group 1(spontaneously breathing model), 26.8% ± 3.1% of the simulated mucus was displaced proximally, compared to 0% in Group 2(the mechanically ventilated model) with a P-value of < 0.01. In fact, 17% ± 1.5% of the mucus in Group 2 remained in the mid-portion of the ETT where it was initially instilled and 80% ± 4.2% was displaced distally back towards the lung(P < 0.01). There was an overall statistically significant amount of mucusmovement proximally towards the mouth-piece in the spontaneously breathing(SB) patient. There was also an overall statistically significant amount of mucus movement distally back towards the lung in the mechanically ventilated(MV) model. In the mechanically ventilated model, no mucus was observed to move towards the proximal/mouth piece section of the ETT. CONCLUSION This bench model suggests that IPV is associated with displacement of mucus towards the proximal mouthpiece in the SB patient, and distally in the MV model.展开更多
The rapid diffusion of nanoparticles （NPs） through mucus layer is critical for efficient transportation of NPs-loaded drug delivery system. To understand how the physical and surface properties of NPs affect their d...The rapid diffusion of nanoparticles （NPs） through mucus layer is critical for efficient transportation of NPs-loaded drug delivery system. To understand how the physical and surface properties of NPs affect their diffusion in mucus, we have developed a coarse-grained molecular dynamics model to study the diffusion of NPs in modeled mucus layer. Both steric obstruction and hydrodynamic interaction are included in the model capable of capturing the key characteristics of NPs＇ diffusion in mucus. The results show that both particle size and surface properties significantly affect the diffusivities of NPs in mucus. Furthermore, we find rodlike NPs can gain a higher diffusivity than spherical NPs with the same hydrodynamic diameter. In addition, the disturbed environment can enhance the diffusivity of NPs. Our findings can be utilized to design mucus penetrating NPs for targeted drug delivery system.展开更多
基金supported by Hong Kong Research Grants Council General Research Fund(CUHK 14102321,14103722 and 14104923)。
文摘Oxidized cholesterol(OXC)is a harmful dietary substance.Although the consumption of OXC has been associated with colonic inflammation,related underlying mechanisms are still limited.We evaluated the influence of dietary OXC on gut health and ecology by applying the murine model.Results showed that the thickness of the mucus layer was significantly reduced in healthy mice treated with OXC.Short-term intake of OXC did not influence the expression of pro-inflammatory factors in healthy mice but it induced the decrease of Muc2 expression in the proximal colon,accompanied by an increase in the abundance of 2 mucusdegrading bacteria,namely Akkermansia muciniphila and Bacteroides acidifaciens.Consistently,oral exposure of OXC promoted mucus barrier erosion in dextran sulfate sodium(DSS)-induced colitis mice and facilitated bacteria infiltration in the colon.The adverse effect of OXC on mucus layer disappeared in antibiotics-treated healthy mice,suggesting that the damaging effect of OXC on the gut mucus layer was not direct and instead was mediated by causing microbiota dysbiosis.Finally,the impact of OXC on the mucus layer and colitis was partly alleviated by green tea catechins.These studies demonstrated that the OXC-induced mucus barrier damage was mainly induced by the dysregulation of gut microbiota at least in this mouse model.
基金supported by the National Natural Science Foundation of China(No.52273123)the Natural Science Foundation of Chongqing,China(No.CSTB2022NSCQ-MSX0474)the Talent-introduction Program of Chongqing Medical and Pharmaceutical College(No.YGZRC2023103).
文摘Dry powder inhalation represents a promising approach for the treatment of lung cancer,offering several advantages such as enhanced targeting,improved bioavailability,and reduced toxicity.However,traditional dry powder formulations suffer from limitations,notably low pulmonary delivery efficiency and inadequate penetration into tumor tissues,thereby limiting their therapeutic efficacy.In response to these challenges,we have developed an innovative trojan horse strategy,harnessing an inhalable nanoparticlein-microsphere system characterized by tunable size,reversible charge,and mucus-penetrating capabilities.The inhalable nanoparticle-in-microsphere system exhibit stable structural properties,excellent environmental responsiveness and high biocompatibility.More importantly,the therapeutic effect of MTX@PAMAM@HA@Gel(MPHG)was demonstrated in vitro and in vivo.This system offers improved pulmonary delivery efficiency,enhanced drug retention within tumor tissues,and effective penetration,thus representing a promising strategy in lung cancer treatment.
基金the financial support from the National Natural Science Foundation of China(Nos.82003678,82222066,82025032)Chinese Pharmacopoeia Commission(No.2021Y30)。
文摘Local delivery of nanoparticles holds promise for colorectal cancer(CRC)therapy.However,the presence of the mucus layer on the epithelium poses a significant challenge to drug delivery,thereby adversely affecting treatment efficiency.It is crucial to develop efficient drug delivery carriers that can effectively overcome mucus barriers to treat colorectal cancer.Herein,we utilized poly(1,4-butadiene)-b-poly(ethylene oxide)polymers to prepare four distinct geometries of polymeric micelles,namely linear micelles(LMs),worm-like micelles(WLMs),large spherical micelles(LSMs),and small spherical micelles(SSMs)to investigate the influence of shape effects on overcoming colonic mucosal barrier.We found that the carriers exhibited diverse shapes while maintaining comparable physicochemical properties.Of these,WLMs had an aspect ratio similar to segmented filamentous bacteria,which exhibited superior mucus penetration ability,leading to prolonged drug release kinetics and faster entry into epithelial cells compared to LSMs.Furthermore,rectally administrated 10-hydroxycamptothecin-loaded WLMs traversed the colorectal mucus in orthotopic CRC nude mice model,penetrated and accumulated within tumor tissue,and effectively aggregated within cancer cells,thereby inducing significantly robust antitumor outcomes in vivo.These findings underscore the significance of shape design in overcoming colonic mucosal absorption barriers,offering a novel approach for the development of drug delivery carriers tailored for effective tumor therapy.
基金support from the National Natural Science Foundation of China(81173010).
文摘Mucus can effectively protect the exposed mucosal surfaces due to its adhesive and viscoelastic properties.Most foreign particulates are efficiently trapped in mucus layers via steric obstruction and adhesion.Trapped particles are typically removed from the mucosal tissue within seconds to a few hours depending on their location sites.This article focuses on describing the tenacious mucus barrier properties,the strategies to investigate the interaction of nanoparticles with the mucus as well as the novel developments of mucus penetrating nanoparticles.
基金Supported by National Natural Science Foundation of China,No.81270471
文摘To reduce medication for patients with ulcerative colitis(UC),we need to establish the etiology of UC.The 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 localization.Small intestinal bacterial overgrowth is significantly higher in IBD patients compared with controls.Probiotics have been investigated for their capacity to reduce the severity of UC.The luminal surfaces of the gastrointestinal tract are covered by a mucus layer.This 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 bacteria.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 rinsing.Some bacteria can dissolve the protective inner mucus layer.Defects in renewal and formation of the inner mucus layer allow bacteria to reach the epithelium and have implications for the causes of colitis.In this review,important elements of UC pathology are thought to be the intestinal bacteria,gut mucus,and the mucosa-associated immune system.
基金Supported by Polish Ministry of Science and Higher Education,Grant No.3PO5E09125
文摘AIM:To assess the mucosa-associated bacterial microflora and mucus layer in adolescents with inflammatory bowel disease(IBD) .METHODS:Sixty-one adolescents(mean age 15 years,SD ± 4.13) were included in the study.Intestinal biopsies from inflamed and non-inflamed mucosa of IBD patients and from controls with functional abdominal pain were cultured under aerobic and anaerobic conditions.The number of microbes belonging to the same group was calculated per weight of collected tissue.The mucus thickness in frozen samples was measured under a fluorescent microscope.RESULTS:The ratios of different bacterial groups in inflamed and non-inflamed mucosa of IBD patients and controls were specific for particular diseases.Streptococcus spp.were predominant in the inflamed mucosa of Crohn's disease(CD) patients(80% of all bacteria) ,and Lactobacillus spp.were predominant in ulcerative colitis patients(90%) .The differences were statistically significant(P = 0.01-0.001) .Lower number of bifidobacteria was observed in the whole IBD group.A relation was also found between clinical and endoscopic severity and decreased numbers of Lactobacillus and,to a lesser extent,of Streptococcus in biopsies from CD patients.The mucus layer in the inflamed sites was significantly thinner as compared to controls(P = 0.0033) and to non-inflamed areas in IBD patients(P = 0.031) .CONCLUSION:The significantly thinner mucosa of IBD patients showed a predominance of some aerobes specific for particular diseases,their numbers decreased in relation to higher clinical and endoscopic activity of the disease.
文摘Objective:To study the antimicrobial,hemolytic activity and immunomodulatory activity of fish epidermal mucus and their chemical constituents from Cynoglossus arel(C.arel) and Alius caelatus(A.caelatus).Mucus plays an important role in the prevention of colonization by parasites,bacteria and fungi.Methods:Epidermal mucus was obtained from two marine fishes,lyophilized and the chemical composition of epidermal mucus was analysed by FT-IR analysis.The in vitro antimicrobial activity against human pathogens(fungi,gram positive and gram-negative bacteria) and also the hemolytic activity and immunomodulatory activity were determined.Results:Totally ten human pathogens were tested against the fish mucus.Out of the ten pathogens,five pathogens have proved to be sensitive to the mucus.Maximum zone of inhibition was observed against Vibrio cholera(V.cholera)(9 mm and 2 mm in diameter),followed by Staphylococcus aureus(S.aureus) with a inhibition zone of(6 mm and 3 mm),Streptococcus areus(S.areus)(5 mm and 4 mm),Vibrio parahemolyticus(V.parahemolyticus)(4 mm and 5 mm) respectively.Conclusions:The present investigation has revealed that positive progresses in the fish mucus extracts against human pathogens and hemolytic activity.But further efforts are required for the purification and isolation of the active antimicrobial compounds in order to establish their possible applications.
基金This study was funded by the National Hi-Tech Development Plan("863"Plan)of China under contract Nos 2001AA5070 and 2002AA639600the Natural Science Foundation of Fujian Province under contract No.B0410022.
文摘Adhesion of Vibrio alginolyticus to the gill mucus of Pseudosciaena crocea has been investigated using [ methyl-^3 H ] thymidine as isotope tracer. The results showed that： the adhesive quantity of V. alginolyticus increased with bacterial concentrations and reached equilibrium after incubated for 180 min; the higher adhesive quantity was obtained at 15 ~ 30 ℃ and sourish conditions; adhesion of V. alginolyticus could not achieved without Na^＋ , and Ca^2＋ played an auxiliary role in the bacterial adhesion; adhesion of V. alginolyticus was inhibited remarkably by starvation, heat treatment and periodic acid treatment; all of the eight kinds of carbohydrates investigated enhanced the adhesion of V. alginolyticus to the gill mucus of P. crocea, among them, glucose, mannose, fructose and maltose showed the specially enhanced adhesion. The results indicated that E alginolyticus could adhere to the gill mucus of P. crocea facilely in seawater, and this bacterial adhesion was influenced by environmental factors and closely related to superficial carbohydrate structures and some heat-sensitive structures.
基金financially supported by the National Natural Science Foundation of China (Grant No. 31870987)
文摘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.
基金financial support received from the National Natural Science Foundation of China(81373356,81573378 and 81703436)the Science and Technology Innovation Action Plan for Basic Research of Shanghai 2014 (14JC1493200)CASIMM0120153020,Shanghai Sailing Program 2017(17YF1423500)
文摘Self-nanoemulsifying systems(SNEs) have excellent ability to improve the solubility ofpoorly water-soluble drugs(PWSD). However, SNEs are likely to be degraded in gastroin-testinal(GIT) when their surface is recognized by lipase/co-lipase enzyme complex, result-ing in rapid release and precipitation of encapsulated drugs. The precipitates are then cap-tured and removed by intestinal mucus, reducing the delivery efficacy of SNEs. Herein, theamphiphilic polymer Pluronic? F127 was incorporated into long and short-chain triglyc-erides(LCT, SCT) based SNEs to diminish the recognition and therefore minimized theirdegradation by enzymes and clearance by mucus. The SNEs were characterized in termsof particle size, zeta potential and stability. Ex vivo multiple particles tracking studies wereperformed by adding particle solution into fresh rat mucus. Cellular uptake of SNEs wereconducted by using E12 cells, the absorption and distribution in small intestine were alsostudied after oral administration in male Sprague-Dawley(SD) rats. The in vitro digestionrate of SNEs were found to be in following order SCT-SNE > SCT-F127-SNE > LCT-SNE > LCT-F127-SNE. Moreover, the LCT-F127-SNE was found to be most effective in enhancing cellularuptake, resulting in 3.5-fold, 2.1-fold and 1.7-fold higher than that of SCT-SNE, LCT-SNE andSCT-F127-SNE, respectively. After incubating the SNE with E12 cells, the LCT-F127-SNE ex-hibited the highest amount regarding both mucus penetration and cellular uptake, with anuptake amount number(via bicinchoninic acid(BCA) analysis) of 3.5-fold, 2.1-fold and 1.7-fold higher than that of SCT-SNE, LCT-SNE and SCT-F127-SNE, respectively. The in vivo results revealed that orally administered LCT-F127-SNE could significantly increase the bioavailability of Cyclosporine A(CsA), which was approximately 2.43-fold, 1.33-fold and 1.80-fold higher than that of SCT-SNE, SCT-F127-SNE and LCT-SNE, respectively. We address in this work that F127-modified SNEs have potentials to improve oral drug absorption by significantly reducing gastrointestinal enzymatic degradation and simultaneously enhancing mucus penetration.
基金Supported by the National High Technology Research and Development Program of China(863 Program)(No.2007AA09Z115)Technology Program of Xiamen(No.3502Z20073019)
文摘Vibriofluvialis incubated in trypticase soy broth （TSB） showed stronger adhesion to the skin mucus of Epinephelus awoara than V. fluvialis grown on trypticase soy agar （TSA）, and this bacterial adhesion was assessed in terms of saturation kinetics. Treating bacteria with antibody against O-antigens resulted in significantly reduced bacterial adhesion. In the early growth stage, the adhering bacteria numbers increased with incubation time, peaked at 24 h, and then dropped sharply. Prior heat treatment of the mucus at various temperatures resulted in different effects on bacterial adhesion. No remarkable effect on bacterial adhesion was detected after treating mucus with protease K and trypsin, whereas periodic acid treatment significantly enhanced bacterial adhesion. Extracts of K fluvialis surface structures at high concentrations significantly inhibited bacterial adhesion, while relatively low concentrations enhanced adhesion. V. fluvialis had strong affinity for a high molecular weight mucus component. These results indicate that V.fluvialis adhered strongly to E. awoara mucus by specific adhesion and that this adhesion was influenced by many factors, including bacterial conditions, mucus, and the environment.
文摘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.
文摘Objective Mucus forms the physical barrier along the gastrointestinal(GI)tract.It plays an important role to prevent mucosal damage and inflammation.Our previous finding showed that antibacterial peptide 'cathelicidin' increased mucus thickness and prevented inflammation in the colon.In the current study,we examined the protective mechanisms by which the peptide increased mucus synthesis in vitro.Methods Human colonic cell line(HT-29)was used to assess the stimulatory action of cathelicidin on mucus synthesis which was measured by the D-[6-3H] glucosamine incorporation assay.Results Human cathelicidin(LL-37)dose-dependently(10-40 μg·mL-1)and significantly stimulated mucus synthesis.Real-time PCR data showed that addition of LL-37 induced more than 50% increase in MUC1 and MUC2 mRNA levels.Treatment with MUC1 and MUC2 siRNAs normalized the stimulatory action of LL-37 on mucus synthesis.LL-37 also activated the phosphorylation of mitogen-activated protein(MAP)kinase in the cells.A specific inhibitor of the MAP kinase pathway,U0126,completely blocked the increase of MUC1 and MUC2 expression as well as mucus synthesis by LL-37.Conclusions Taken together LL-37 stimulates mucus synthesis through the activation of MUC1 and MUC2 expression and the MAP kinase pathway in human colonic cells.
文摘The aim of this study was to investigate whether a relationship exists between the presence of low numbers of leukocytes in normal ovulatory cervical mucus and sperm quality and lipid content after migration. The percentages of live, motile and morphologically normal spermatozoa, movement parameters assessed by computer-aided sperm analysis （CASA）, and ionophore-induced acrosome reaction measured by flow cytometry were determined before and after migration. High-performance liquid chromatography with ultraviolet detection was used to measure the sperm lipid content, including the various diacyl subspecies. The number of leukocytes found in solubilized mucus samples was counted using a haemocytometric method. Overall, the presence of leukocytes in the cervical mucus samples did not significantly influence sperm motility and morphology, sperm kinematic parameters, or the sperm content in sphingomyelin or cholesterol. In contrast, after migration, the decrease in various sperm diacyls and the level of induced acrosome reaction was significantly less pronounced in mucus samples containing ≥10^4 leukocytes than in mucus samples with no or rare leukocytes whereas the level of induced acrosome reaction was higher. The present data suggest that the low level of leukocytes found in normal ovulatory cervical mucus could influence the process of sperm lipid remodelling/capacitation.
基金financially supported by the National Natural Science Foundation of China(Nos.20674072 and 51173164)
文摘Loach skin mucin was isolated from loach skin mucus and found to be similar to mammalian mucins in many aspects, i.e., low amino acid residue content, high molecular weight, presence of hydrophobic blocks and gel-forming characteristics in water. However, loach skin mucin can form a weak gel in water at a much lower concentration （3 mg/mL） than mammalian mucins, indicating its good hydrophilicity. Loach skin mucin can also form a stable adsorption layer on gold surface in aqueous environment, owing to the existence of hydrophobic blocks within mucin. The nature of high hydrophilicity and interfacial behavior give loach skin mucin potential as excellent material for use in solid-water interfaces for antifouling and lubrication, and should be crucial to the versatile functions of loach skin mucus.
文摘Little was known about mammalian colon mucus(CM)until the beginning of the 21^(st) century.Since that time considerable progress has been made in basic research addressing CM structure and functions.Human CM is formed by two distinct layers composed of gel-forming glycosylated mucins that are permanently secreted by goblet cells of the colonic epithelium.The inner layer is dense and impenetrable for bacteria,whereas the loose outer layer provides a habitat for abundant commensal microbiota.Mucus barrier integrity is essential for preventing bacterial contact with the mucosal epithelium and maintaining homeostasis in the gut,but it can be impaired by a variety of factors,including CM-damaging switch of commensal bacteria to mucin glycan consumption due to dietary fiber deficiency.It is proven that impairments in CM structure and function can lead to colonic barrier deterioration that opens direct bacterial access to the epithelium.Bacteria-induced damage dysregulates epithelial proliferation and causes mucosal inflammatory responses that may expand to the loosened CM and eventually result in severe disorders,including colitis and neoplastic growth.Recently described formation of bacterial biofilms within the inner CM layer was shown to be associated with both inflammation and cancer.Although obvious gaps in our knowledge of human CM remain,its importance for the pathogenesis of major colorectal diseases,comprising inflammatory bowel disease and colorectal cancer,is already recognized.Continuing progress in CM exploration is likely to result in the development of a range of new useful clinical applications addressing colorectal disease diagnosis,prevention and therapy.
文摘Colonoscopy is currently the gold standard for diagnosis of inflammatory bowel disease(IBD)and colorectal cancer(CRC).This has the obvious drawback of being invasive as well as carrying a small risk.The most widely used non-invasive approaches include the use of faecal calprotectin in the case of IBD and fecal immunochemical test in the case of CRC.However,the necessity of stool collection limits their acceptability for some patients.Over the recent years,there has been emerging data looking at the role of non-invasively obtained colorectal mucus as a screening and diagnostic tool in IBD and CRC.It has been shown that the mucus rich material obtained by self-sampling of anal surface following defecation,can be used to measure various biomarkers that can aid in diagnosis of these conditions.
基金This work was supported by the National Natural Science Foundation of China under contract No.40576052the Scientific Research Foundation of China Three Gorges University under contract No.0620060113.
文摘Coral mucus covers the surface of coral and contains antibacterial substances as a first line of defense. Coral mucus not only enables the coral itself to resist disease, but also provides antibacterial agents for people. We collected mucus from a scleractinian coral （Symphyllia gigantea） at Sta. Sanya （China）, then extracted the antibacterial substances using 10% glacial acetic acid with the help of antiprotease inhibitors, and tested the antibacterial activity by a terrestrial bacterium （Staphylococcus aurevs） and a marine bacterium （Vibrio anguillarum）. The result showed that, there were antibacterial agents in the mucus, and their antibacterial activities were lost by treatment of the sample at 90 ℃ water for 10 min.
文摘AIM To determine the ability of intrapulmonary percussive ventilation(IPV) to promote airway clearance in spontaneously breathing patients and those on mechanical ventilation.METHODS An artificial lung was used to simulate a spontaneously breathing patient(Group 1), and was then connected to a mechanical ventilator to simulate a patient on mechanical ventilation(Group 2). An 8.5 mm endotracheal tube(ETT) connected to the test lung, simulated the patient airway. Artificial mucus was instilled into the mid-portion of the ETT. A filter was attached at both ends of the ETT to collect the mucus displaced proximally(mouth-piece filter) and distally(lung filter). The IPV machine was attached to the proximal end of the ETT and was applied for 10-min each to Group 1 and 2. After each experiment, the weight of the various circuit components were determined and compared to their dry weights to calculate the weight of the displaced mucus.RESULTS In Group 1(spontaneously breathing model), 26.8% ± 3.1% of the simulated mucus was displaced proximally, compared to 0% in Group 2(the mechanically ventilated model) with a P-value of < 0.01. In fact, 17% ± 1.5% of the mucus in Group 2 remained in the mid-portion of the ETT where it was initially instilled and 80% ± 4.2% was displaced distally back towards the lung(P < 0.01). There was an overall statistically significant amount of mucusmovement proximally towards the mouth-piece in the spontaneously breathing(SB) patient. There was also an overall statistically significant amount of mucus movement distally back towards the lung in the mechanically ventilated(MV) model. In the mechanically ventilated model, no mucus was observed to move towards the proximal/mouth piece section of the ETT. CONCLUSION This bench model suggests that IPV is associated with displacement of mucus towards the proximal mouthpiece in the SB patient, and distally in the MV model.
基金the financial support from the National Natural Science Foundation of China (No. 11422215, 11272327 and 11672079)supported by the Supercomputing Center of Chinese Academy of Sciences (SC CAS)
文摘The rapid diffusion of nanoparticles （NPs） through mucus layer is critical for efficient transportation of NPs-loaded drug delivery system. To understand how the physical and surface properties of NPs affect their diffusion in mucus, we have developed a coarse-grained molecular dynamics model to study the diffusion of NPs in modeled mucus layer. Both steric obstruction and hydrodynamic interaction are included in the model capable of capturing the key characteristics of NPs＇ diffusion in mucus. The results show that both particle size and surface properties significantly affect the diffusivities of NPs in mucus. Furthermore, we find rodlike NPs can gain a higher diffusivity than spherical NPs with the same hydrodynamic diameter. In addition, the disturbed environment can enhance the diffusivity of NPs. Our findings can be utilized to design mucus penetrating NPs for targeted drug delivery system.
