Bovine Mucus Research Articles

A simple and reliable refractometric method to determine the total solids concentration of the cervico-vaginal bovine mucus samples

Cervico-vaginal mucus (CVM) is a viscoelastic substance continuously produced by secretory cells of the endocervix and the vagina of cows. Its physicochemical composition varies depending on the hormonal status of the estrous cycle. In veterinary medicine refractometry is a widely diffused technique to determine total solids (TS) content of biological samples, but there are not published data of CVM total solids from refractometric measures. Refractometric TS determination contributes to the qualitative constituents analysis of CVM, additionally it is an easier and more inexpensive technique than gravimetric TS determination. The main goal of the present paper was to validate a refractometric method to estimate TS concentration of the soluble fraction of CVM samples. Samples were collected from seventy-three Holando Argentino cows of Santa Fe province farms in Argentina. Cows were classified in three experimental groups: healthy, subclinical (SE) and clinical endometritis (CE) group. To achieve a solubilisation protocol for CVM samples, four Triton™ X-100 concentrations were tested. Refractive index (RI) and gravimetric total solid (gTS) concentration of solubilised samples were determined for the three experimental groups. A mathematical equation was determined with the experimental data from the healthy group, in order to obtain calculated total solid concentration (cTS) from refractivity (R) values. To validate the RI method for CVM samples, cTS concentrations were compared with gTS concentrations from endometritis group samples. Triton™ X-100 0.01% (V/V) improved CVM samples handling and did not change physicochemical parameters (gTS, Na+ and K+ concentration, and RI values). The linear regression equation obtained was: cTS (g/dL) = (R – 0.67)/16.2, r2 = 0.91. Correlation between gTS and cTS concentration was: r = 0.97 for SE group and r = 0.97 for CE group. The homogenization protocol allowed the measurement of physicochemical parameters without altering their values. A high correlation coefficient between cTS and gTS postulates refractometry as an accurate method to determine TS concentration for solubilised CVM samples.

Examination of oestrus-dependent alterations of bovine cervico-vaginal mucus glycosylation for potential as optimum fertilisation indicators.

Oestrus is the period in the sexual cycle of female mammals where they become most receptive to mating and are most fertile. Efficient detection of oestrus is a key component in successful reproductive livestock management programmes. Oestrus detection in cattle is most often performed by visual observation, such as mounting behaviour and standing heat, to facilitate more successful prediction of optimal time points for artificial insemination. This time-consuming method requires a skilled, diligent observer. Biological measurements using easily accessible biomolecules in the cervico-vaginal mucus could provide an alternative strategy to physical methods of oestrus detection, providing an inexpensive means of rapidly and accurately assessing the onset of oestrus. In this study, glycosylation changes in cervico-vaginal mucus from three heifers following oestrus induction were investigated as a proof of concept to assess whether potential glycosylation-based trends could be useful for oestrus stage indication. Mucus collected at different time points following oestrus induction was immobilised in a microarray format and its glycosylation interrogated with a panel of fluorescently labelled lectins, carbohydrate-binding proteins with different specificities. Individual animal-specific glycosylation patterns were observed, however each pattern followed a similar trend around oestrus. This unique oestrus-associated glycosylation was identified by a combination of relative binding of the lectins SNA-I and WFA for each animal. This alteration in cervico-vaginal mucus glycosylation could potentially be exploited in future to more accurately identify optimal fertilisation intervention points compared to visual signs. More effective oestrus biomarkers will lead to more successful livestock reproductive programmes, decreasing costs and animal stress.

Diffusions of β-cyclodextrins in mucus studied by 19F diffusion NMR

β-Cyclodextrin (β-CD) based materials have been widely used as drug carriers for pharmaceutical applications. To understand the diffusion of β-CDs in mucus is important for selecting β-CD based drug carriers for applications targeting mucosal absorption because the surfaces of many biological membranes are covered with a highly viscous aqueous mucus layer which forms relatively effective diffusion barriers for drugs. In this study, 19F self-diffusion NMR technique has been applied to study the self-diffusions of β-CDs in mucus. The 19F NMR signals arose from 1-fluoroadamantane molecules entrapped in the cavities of β-CDs. The diffusive abilities of different β-CDs in mucus were assessed through analyzing the diffusion coefficients using the presented kinetic model, and Ogston’s and Renkin’s diffusion models for hydrogel systems. The kinetic results show that 2-hydroxypropyl-β-CD and 2-Carboxyethyl-β-CD have the smallest binding affinities to bovine submaxillary mucin and human nasal mucin among five tested β-CDs. The mesh sizes of the bovine submaxillary mucus at different concentrations and that of the human nasal mucus were evaluated using the diffusion models. We hope that this 19F diffusion method will be useful to study the diffusion of β-CD based materials in other biological systems.

Mucoadhesive liposomes as new formulation for vaginal delivery of curcumin

Local delivery to the affected area represents the optimal means by which advantageous pharmacological properties of curcumin may be fully exploited as currently, due to the biopharmaceutical limitations associated with this polyphenol, its full beneficial effects remain limited. Curcumin-containing liposomes coated with bioadhesive polymers of natural and synthetic origin (chitosan and Carbopol) were evaluated in vitro. For these purposes, an in vitro model of vaginal mucus was developed allowing the monitoring of curcumin permeability in the conditions mimicking vaginal environment. The model was optimized by varying the amounts of glycoproteins, as compared to the permeabilities determined through isolated bovine mucus. The strength of bioadhesion was evaluated using the isolated bovine mucosa. Both curcumin solution and non-coated curcumin liposomes served as controls. Bioadhesive polymers enabled significantly higher (p<0.05) curcumin permeability through the artificial and isolated bovine mucus compared to the controls. Polymer coating of liposomes resulted in an increase in their bioadhesiveness. Mucoadhesive liposomes can be considered as potential novel drug delivery systems intended for vaginal administration of curcumin.

Diffusion against convection

I read with great interest the recent paper entitled “Convective washout reduces antidiarrheal efficacy of enterocyte surface–targeted antisecretory drugs” by Jin et al. (2013) in the February 2013 issue of the Journal. In this paper, the influence on drug diffusion of adverse fluid convection was modeled by solving a diffusion convection equation with appropriate boundary conditions. In effect, the paper models the likelihood that solute can travel from the mucosal surface to the crypts in the face of adverse fluid secretion. The concept of normal intestinal secretion from the enterocytes has been advocated many times, but its existence and function have periodically been questioned, as early as the late nineteenth century (Hoppe-Seyler, 1879). The need for luminally directed movement of fluid specifically to flush material or harmful bacteria away from the mucosal surface was advocated by Pavlov (1897) as itself confirming the existence of fluid secretion as a normally occurring physiological event. Although it can also be argued that secretion has no obvious normal physiological function (Lucas, 2010), the concept of an antibacterial purpose to secretion arises often (Barrett and Keely, 2000), as well as a putative need for secretion to transport in a timely way crypt cell products to the tips of the villi. Despite this, there are very few published solutions to this diffusion–convection problem, and the present authors are to be commended for providing one. If their input values are accepted, it seems clear that normal secretion rates close to those observed in extreme cases of cholera (Fig. 2 of Jin et al., 2013) would be required to keep the mucosal surface free of bacteria. This is evident when the diffusion coefficient for bacteria is taken into account, as this can be of the order of 10−5 cm2 sec−1 (Kiorboe et al., 2002) for some bacteria. At rates of fluid velocity that are allegedly normal, i.e., required by the premise that the small intestine normally secretes one liter of fluid per day, the Peclet number is likely to be far less than that assumed by the authors and insufficient to keep bacteria off the mucosal surface. The argument for normally occurring rates of secretion having a hygienic function seems fatally undermined by the calculations provided by the authors. However, a concern that should be expressed is that the theoretical values selected by the authors may vary by an order of magnitude from real values. On the question of what constitutes reasonable values for convection and diffusion in the crypts, it may be that the authors have overestimated the velocity of convection and underestimated the diffusion coefficient within the crypts. In their Table 1 of baseline parameters, the diffusion coefficient in the crypt/villus region is estimated to be one tenth of the value in the intestinal lumen and implies that free diffusion does not occur within the fluid between the villi because of the presence of mucus. There is no doubt that viscosity is increased by mucus, but it is unlikely that diffusion is reduced to the extent that the authors assume. Using bovine mucus at a concentration of 10%, which had an extremely high viscosity, the reduction in the diffusion coefficient was estimated to be only 30% (Lucas, 1984), which meant that the diffusion coefficient was 70% of the normal value in aqueous solution. This could be higher with the concentrations of mucus that occur physiologically within the inter-villus space. In set agar as opposed to mucus in the flowing state, no reduction in diffusion coefficients is found (Schantz and Lauffer, 1962); hence, the selection by the authors of a diffusion coefficient that is one tenth of normal would need to be justified. Accordingly, it would be interesting to know how the authors’ calculations might change when the diffusion coefficient within the cryptal and inter-villus space is assumed to equal the value in aqueous solution and also when rates of secretion are not set to the extremely high value that occurs in cases of cholera.

Screening of an E. coli O157:H7 Bacterial Artificial Chromosome Library by Comparative Genomic Hybridization to Identify Genomic Regions Contributing to Growth in Bovine Gastrointestinal Mucus and Epithelial Cell Colonization.

Enterohemorrhagic E. coli (EHEC) O157:H7 can cause serious gastrointestinal and systemic disease in humans following direct or indirect exposure to ruminant feces containing the bacterium. The main colonization site of EHEC O157:H7 in cattle is the terminal rectum where the bacteria intimately attach to the epithelium and multiply in the intestinal mucus. This study aimed to identify genomic regions of EHEC O157:H7 that contribute to colonization and multiplication at this site. A bacterial artificial chromosome (BAC) library was generated from a derivative of the sequenced E. coli O157:H7 Sakai strain. The library contains 1152 clones averaging 150 kbp. To verify the library, clones containing a complete locus of enterocyte effacement (LEE) were identified by DNA hybridization. In line with a previous report, these did not confer a type III secretion (T3S) capacity to the K-12 host strain. However, conjugation of one of the BAC clones into a strain containing a partial LEE deletion restored T3S. Three hundred eighty-four clones from the library were subjected to two different selective screens; one involved three rounds of adherence assays to bovine primary rectal epithelial cells while the other competed the clones over three rounds of growth in bovine rectal mucus. The input strain DNA was then compared with the selected strains using comparative genomic hybridization (CGH) on an E. coli microarray. The adherence assay enriched for pO157 DNA indicating the importance of this plasmid for colonization of rectal epithelial cells. The mucus assay enriched for multiple regions involved in carbohydrate utilization, including hexuronate uptake, indicating that these regions provide a competitive growth advantage in bovine mucus. This BAC-CGH approach provides a positive selection screen that complements negative selection transposon-based screens. As demonstrated, this may be of particular use for identifying genes with redundant functions such as adhesion and carbon metabolism.

Penetration ability of human spermatozoa into standardized bovine cervical mucus (Penetrak) in patients with normal and pathological semen samples.

Semen samples from 89 men were analyzed and evaluated with a standardized bovine cervical mucus penetration test (Penetrak). 29 patients had a normozoospermia, 22 patients a teratozoospermia and 38 patients an oligozoospermia of various degree. The most important parameters of semen analysis were compared with sperm mucus penetration. The sperm mucus penetration test correlated best with progressive motility (r = 0.6758), followed by total motility (r = 0.6302), sperm count (r = 0.6190), and % normal spermatozoa (r = 0.5493) (p less than 0.01 for each correlation coefficient). In the group of patients with normozoospermia 6 cases had been detected with insufficient sperm mucus penetration and in both groups with subfertility 15 cases with adequate sperm mucus penetration. 8 semen samples with normal sperm count and normal sperm motility were used for IVF. Only 6 patients with normal sperm penetration (greater than 30 mm/90') the spermatozoa fertilized the ova, but not from two patients, who had a sperm mucus penetration of less than 30 mm/90'. The study demonstrated that standardized bovine mucus penetration test detects disturbances of sperm motility which may not be discovered by conventional semen analysis.

Host Protein Binding and Adhesive Properties of H6 and H7 Flagella of Attaching and Effacing Escherichia coli

It had been suggested that the flagella of enteropathogenic Escherichia coli (EPEC) and enterohemorrhagic E. coli (EHEC) might contribute to host colonization. In this study, we set out to investigate the adhesive properties of H7 and H6 flagella. We studied the abilities of EHEC EDL933 (O157:H7) and EPEC E2348/69 (O127:H6) flagella to bind to bovine mucus, host proteins such as mucins, and extracellular matrix proteins. Through several approaches, we found that H6 and H7 flagella and their flagellin monomers bind to mucins I and II and to freshly isolated bovine mucus. A genetic approach showed that EHEC and EPEC fliC deletion mutants were significantly less adherent to bovine intestinal tissue than the parental wild-type strains. In addition, we found that EPEC bacteria and H6 flagella, but not EHEC, bound largely, in a dose-dependent manner, to collagen and to a lesser extent to laminin and fibronectin. We also report that EHEC O157:H7 strains agglutinate rabbit red blood cells via their flagella, a heretofore unknown phenotype in this pathogroup. Collectively, our data demonstrate that the H6 and H7 flagella possess adhesive properties, particularly the ability to bind mucins, that may contribute to colonization of mucosal surfaces.

Application of Bacteriophages To Control Intestinal Escherichia coli O157:H7 Levels in Ruminants

A previously characterized O157-specific lytic bacteriophage KH1 and a newly isolated phage designated SH1 were tested, alone or in combination, for reducing intestinal Escherichia coli O157:H7 in animals. Oral treatment with phage KH1 did not reduce the intestinal E. coli O157:H7 in sheep. Phage SH1 formed clear and relatively larger plaques on lawns of all 12 E. coli O157:H7 isolates tested and had a broader host range than phage KH1, lysing O55:H6 and 18 of 120 non-O157 E. coli isolates tested. In vitro, mucin or bovine mucus did not inhibit bacterial lysis by phage SH1 or KH1. A phage treatment protocol was optimized using a mouse model of E. coli O157:H7 intestinal carriage. Oral treatment with SH1 or a mixture of SH1 and KH1 at phage/bacterium ratios > or = 10(2) terminated the presence of fecal E. coli O157:H7 within 2 to 6 days after phage treatment. Untreated control mice remained culture positive for >10 days. To optimize bacterial carriage and phage delivery in cattle, E. coli O157:H7 was applied rectally to Holstein steers 7 days before the administration of 10(10) PFU SH1 and KH1. Phages were applied directly to the rectoanal junction mucosa at phage/bacterium ratios calculated to be > or = 10(2). In addition, phages were maintained at 10(6) PFU/ml in the drinking water of the phage treatment group. This phage therapy reduced the average number of E. coli O157:H7 CFU among phage-treated steers compared to control steers (P < 0.05); however, it did not eliminate the bacteria from the majority of steers.

DNA Diffusion in Mucus: Effect of Size, Topology of DNAs, and Transfection Reagents

DNA represents a promising therapeutic and prophylactic macromolecule in treating genetic diseases, infectious diseases and cancers. The therapeutic potential of DNA is directly related to how DNA transports within the targeted tissue. In this study, fluorescence photobleaching recovery was used to examine the diffusion of plasmid DNAs with various size (2.7 ∼ 8.3 kb), topology, and in the presence of transfection reagents in mucus. We observed that DNAs diffused slower when size of DNAs increased; supercoiled DNAs diffused faster than linear ones; mucus did not reduce the diffusion of linear DNAs but retarded the diffusion of supercoiled DNAs. Diffusion data were fitted to models of a polymer chain diffusing in gel systems. Diffusion of linear DNAs in mucus were better described by the Zimm model with a scaling factor of −0.8, and supercoiled DNAs showed a reptational behavior with a scaling factor of −1.3. Based on the Zimm model, the pore size of bovine mucus was estimated and agreed well with previous experimental data. In the presence of transfection reagents, e.g., liposomes, the diffusion of DNAs increased by a factor of 2 in mucus. By using bovine mucus as a model system, this work suggests that DNA size, topology, and the presence of transfection reagents may affect the diffusion of DNA in tissues, and thus the therapeutic effects of DNA.

Pokeweed antiviral protein: a potential nonspermicidal prophylactic antiviral agent

Objective: To investigate the effects of pokeweed antiviral protein (PAP), a 29-kDa anti-human immunodeficiency virus (HIV) protein purified from the leaves of Phytolacca americana, on human sperm function. Design: Prospective, controlled study. Setting: Reproductive biology department. Patient(s): Seven sperm donors. Intervention(s): Human sperm and female genital tract epithelial cells were exposed to PAP ranging in concentration from 1 to 1,000 μg/mL. Main Outcome Measures: Effect of PAP on sperm motility, kinematics, and sperm penetration through bovine mucus, as well as binding, penetration, and fusion of zona-free hamster eggs. Results: Exposing human sperm to PAP (IC 50 p24 = 14 ± 2 nM) did not affect sperm motility and kinematics over a dose range of 1 to 1,000 μg/mL. Treating sperm with either 100 or 1,000 μg/mL of PAP had no effect on cervical mucus penetrability, nor did it affect sperm binding, penetration, and fusion of zona-free hamster eggs. PAP was noncytotoxic to genital-tract epithelial cells. Conclusions: The broad-spectrum antiviral agent PAP was nontoxic to human sperm and female genital tract epithelial cells even at a concentration 2,000 times higher than its IC 50 value against HIV-1. PAP has particular clinical usefulness both as a nonspermicidal intravaginal microbicide and as a prophylactic antiviral agent that can inactivate infective viruses and virus-infected cells in semen before assisted reproductive technology procedures are undertaken.

Characterization of Antigenic Proteins from Tritrichomonas foetus Recognized by Antibodies in Rabbit Serum, Bovine serum and Bovine cervicovaginal Mucus

Tritrichomonas foetus is an obligate parasite of the bovine urogenital tract and is recognized as 1 of the more common infectious agents causing decreased reproductive efficiency in beef cattle. Infections result in reproductive failure and produce considerable economic loss. Vaccination of heifers with vaccines containing T. foetus induces elevated serological responses to many T. foetus antigens, decreases the rate and/or length of infection with T. foetus, and decreases fetal loss caused by infection. Because T. foetus infections are usually limited to lumen and mucosal surfaces of the reproductive tract, it has been assumed that protection from infection and abortion is partially mediated by immunoglobulins in the uterus and vagina. The objective of this study was to identify and characterize specific antigens of T. foetus that show promise for use in a recombinant vaccine that will generate a protective mucosal immune response in cattle. Surface proteins were identified by using polyclonal rabbit anti-trichomonal sera eluted from paraformaldehyde-fixed cells. Analyses of these proteins, utilizing mucosal antibodies from vaccinated and convalescent cows, have identified proteins involved in generating a local immune response. Western immunoblot analysis indicates that these proteins are well conserved and are excellent candidates for incorporation into a recombinant vaccine.

Risk factors for antisperm antibodies in infertile men.

The prevalence of anti-sperm antibodies (ASAs) in the general population is 0 to 2%; the prevalence in infertile men is much higher at 7 to 26%. However, the role of ASAs in male infertility remains controversial to date. Although several risk factors for ASA development have been defined (such as testicular torsion, varicocele, cryptorchidism, vasectomy, and genital tract infection), there are no specific indications for ASA testing. In order to examine if a single parameter exists identifying patients with elevated ASA titers, serum ASA testing was performed with an enzyme-linked immunosorbent assay (ELISA) in 226 consecutive male patients. The new assay, synchron ELISA (Synelisa) used in our study represents a new type of ELISA without fixation of the sperm surface antigens by formaldehyde or glutaraldehyde. Therefore, the quantitative assay is highly sensitive and reproducible since the structure of sperm surface antigens is not altered by the fixation process. The prevalence of ASAs in this population was 14%, while the prevalence of the control group was 2.5%. Of all factors analyzed only a history of vasectomy, an acute epididymitis, and an abnormal result in the bovine mucus penetration test was associated with elevated ASA titers (P < .001). In addition, we could demonstrate a time related formation of ASAs in men after vasectomy.

Demonstration of antibodies against Candida guilliermondii var. guilliermondii in asymptomatic infertile men.

Candida guilliermondii (C.g.) occurs mostly in animals, but it can affect humans too. Using serological screening methods studies have been carried out in 57 (30 normozoospermic and 27 oligozoospermic) asymptomatic infertile men, of whom 15 (26.3%; 9 oligozoospermic and 6 normozoospermic) were found to have responded to Candida guilliermondii var. guilliermondii. Sperm parameters (cell count, motility, morphology) were determined and various tests (hypo-osmotic swelling test, bovine mucus penetration, swim-up and testosterone examinations) were also performed. In the C.g.-infected and non-infected groups no significant difference was observed in any of the parameters. Precipitation was performed with a special antigen and in the positive group agglutination titres ranged from 0 to 1/320. Comparing C.g. titres with sperm parameters, only the swim-up technique showed noticeable alteration (P = 0.003). One month following ketoconazole treatment, the patients showed no precipitation reactions and their agglutination titres were < 1/80. Our results suggest that for the diagnosis of male infertility a serologic screening for C.g. is essential. As C.g. can also be sexually transmitted, both the husband and wife must be treated, if infection occurs.

The effect of cocaine on sperm motility characteristics and bovine cervical mucus penetration

To determine the in vitro effects of cocaine on sperm motility and bovine mucus penetration because cocaine abuse is associated with decreased sperm motility, and related compounds, such as procaine, are known to decrease sperm motility. Human semen samples were exposed to a range of cocaine concentrations and the effects quantified using computer-assisted sperm analysis and the bovine mucus penetration test. University research laboratory. Samples were obtained from 18 healthy volunteers. Normal semen samples were exposed to concentrations of cocaine ranging from 10 −11 to 10 −4 M. Motility characteristics were evaluated after 2 hours, and bovine mucus penetration was evaluated after 30 minutes, 1 hour, and 2 hours. Mucus penetration by washed sperm was also evaluated. Motility characteristics were evaluated using computer-assisted sperm analysis, and functional sperm motility was evaluated using the bovine mucus penetration test. Cocaine exposure decreased the percentage of motile sperm in a concentration-dependent manner with a maximum decrease of 23% at 10 −4 M but had no effect on other motility characteristics. Cocaine decreased bovine mucus penetration by 12% at high cocaine concentrations (10 −4 M), but increased penetration by 69% at low concentrations (10 −9 M). Washing sperm before cocaine exposure attenuated the increased sperm penetration. The ability of cocaine to decrease the percentage of motile sperm at high concentrations may explain the decreased sperm motility associated with cocaine use. Cocaine’s ability to augment sperm penetration at low concentrations suggests an interaction of cocaine with the sperm adrenergic system.

Hyaluronic acid as a medium for human sperm migration tests

Hyaluronic acid was used as a substitute for human cervical mucus as a medium for sperm migration since its viscosity, molecular weight and structure are similar to constituent glycoproteins of human cervical mucus. Parameters of sperm motility were comparable in human cervical mucus and hyaluronate as measured by a computerized sperm motion analysis system (Hamilton-Thorn 2030 and Strömberg-Mika System). Sperm migration rates were also similar in human cervical mucus, bovine mucus and hyaluronic acid and the reproducibility was best in hyaluronic acid. Sperm survival for 24 h was maintained in human cervical mucus and hyaluronic acid but not in bovine mucus. The use of hyaluronic acid in sperm migration tests is recommended.

The occurrence of Chlamydia trachomatis in the semen of men participating in an IVF programme.

Chlamydia trachomatis is one of the most common causative agents of sexually transmitted diseases. The authors studied the occurrence of C. trachomatis in the semen of 184 asymptomatic men participating in the IVF programme. Twenty-six (14.1%) of the 184 tested were positive for C. trachomatis, these patients and their wives receiving doxycycline capsules twice, 100 mg on the first day and 100 mg/day for the following 13 days. This treatment was effective in 88.5% of the cases and in the rest, treatment continued with erithromycin 250 mg four times/day for 2 weeks. The authors compared the semen parameters (cell count, motility, morphology, bovine mucus penetration and hypo-osmotic swelling test) in the infected and non-infected groups and observed no significant difference between these two groups.

Bioadhesive analysis of controlled-release systems. I. Fracture and interpenetration analysis in poly(acrylic acid)-containing systems

Novel bioadhesive controlled release tablets were prepared from poly (acrylic acid) and hydroxypropyl methylcellulose. Their bioadhesive behavior was studied in a modified tensile tester in contact with bovine sublingual mucus, and the force-elongation behavior was measured up to the breakpoint. The work of adhesion was calculated and related to bioadhesive characteristics of the tablets. It was found that the bioadhesive bond strength between these tablets and the bovine mucus was a monotonically increasing function of their poly (acrylic acid) content. The bioadhesive results were analyzed in terms of a new theoretical framework based on the fracture and interpenetration (diffusion) theories of bioadhesion. Important molecular parameters were calculated and new bioadhesive correlations were verified.

Bioadhesive analysis of controlled-release systems. II. Time-Dependent bioadhesive stress in poly(acrylic acid)-containing systems

Analysis of the dynamic behavior of the bioadhesive strength is presented for novel controlled release systems containing poly (acrylic acid) and hydroxypropyl methylcellulose. By measuring the stress relaxation behavior of these systems in preswollen form and in contact with sublingual bovine mucus it was possible to examine the effect of their mean relaxation time and permanent deformation on their adhesive behavior.

Bioadhesive analysis of controlled-release systems. III. Bioadhesive and release behavior of metronidazole-containing poly(acrylic acid)-hydroxypropyl methylcellulose systems

Bioadhesive controlled release systems for the delivery of metronidazole were prepared by compression of hydroxypropyl methylcellulose with poly(acrylic acid), which served as the bioactive adhesive compound. The release behavior of systems containing 50 wt% metronidazole and various amounts of the two polymers was found to be non-Fickian. The bioadhesive strength of the bond formed between surface-preswollen systems and the sublingual bovine mucus was determined by novel tensile experiments and it was found to be dependent on the poly( acrylic acid) content.