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Mucoadhesion is a special case of bioadhesion in which a material adheres to soft mucosal tissues. This review elucidates our current understanding of mucoadhesion across length, time, and energy scales by focusing on relevant structural features of mucus. We highlight the importance of both covalent and non-covalent interactions that can be tailored to maximize mucoadhesive interactions, particularly concerning proteinaceous mucoadhesives, which have been explored only to a limited extent so far in the literature. In particular, we highlight the importance of thiol groups, hydrophobic moieties, and charged species inherent to proteins as key levers to fine tune mucoadhesive performance. Some aspects of protein surface modification by grafting specific functional groups or coupling with polysaccharides to influence mucoadhesive performance are examined. Insights from this review offer a physicochemical roadmap to inform the development of biocompatible, protein-based mucoadhesive systems that can fulfil dual roles for both adhesion and delivery of actives, enabling the fabrication of advanced biomedical, nutritional and allied soft material technologies., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier B.V.)

Misoprostol (MSP) is commonly prescribed in obstetrics and gynecology clinical practice for labor induction, cervical ripening, first-trimester pregnancy termination, and the treatment of postpartum hemorrhage. Furthermore, there is a lack of comprehensive discussion evaluating how different commercially available formulations influence the overall efficacy of MSP, even though reports indicate issues with the quality of these formulations, particularly regarding stability and vaginal absorption processes. This study investigates the stability of MSP under acidic conditions and its in vitro permeation using swine vaginal mucosa. A forced degradation study was conducted using 0.2 M HCl, and a high-efficiency LC method was developed. Three degradation products were identified and characterized using electrospray ionization-high-resolution quadrupole-time-of-flight-MS, with respective m/z values of 391.2508, 405.2705, and 387.2259, respectively. These results suggest that the degradation mechanism involves dehydration of the β-hydroxy ketone moiety, followed by isomerization to its most resonance-stable form and de-esterification. Finally, the in vitro permeation study revealed that the esterified form of MSP was unable to permeate the mucosa and required prior degradation for any component to be detected in the receptor fluid., (© 2024 John Wiley & Sons Ltd.)

Background: Loropetalum chinensis (R.Br) Oliv (Bhjm), a Chinese folk herbal medicine, was traditionally used in the treatment of wound bleeding and skin ulcers. A new drug named JIMUSAN granules used for gastrosia was developed by our group, and clinical trials have been approved. However, as the principal herb, the material basis and underlying mechanisms of Bhjm in attenuating gastrointestinal mucosa damage (GMD) remain to be systemically illuminated., Purpose: An integrated strategy was used to explore the therapeutic effects and mechanisms of Bhjm and ellagic acid (EA) on GMD zebrafish, using network pharmacology, transcriptomics, lipidomics, and real-time quantitative PCR (RT-qPCR) verification., Methods: First, network pharmacological analysis was used to infer the major effective constituents and targets of Bhjm. Ultra high performance liquid chromatography-linear ion trap/orbitrap high resolution mass spectrometry (UHPLC-LTQ-Orbitrap HRMS) and ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) were employed to identify the chemical constituents and quantify the different types of constituents. Second, zebrafish model of GMD was established by using 2,4,6-trinitrobenzenesulfonic acid (TNBS) to evaluate the efficacy of Bhjm and EA. The potential mechanism was examined by integrated transcriptomics and lipidomics analysis. Finally, validation tests were implemented using RT-qPCR., Results: In this study, targets indentified by network pharmacology were related to inflammation and mucosal damage. Ten representative components that interacted with these targets were simultaneously determined by UHPLC-MS/MS. Sixty four compounds were identified or tentatively characterized, most of which were flavonoids and polyphenols. Bhjm and EA alleviated mucosal damage and reduced inflammation in a TNBS-induced zebrafish GMD model, indicating that EA was the main active compounds. Eight common differentially expressed genes were downregulated by Bhjm and EA, as determined by transcriptomics analysis. Lipidomics analysis confirmed 12 differential lipids, including phosphatidylcholine (PC) and triglyceride (TG). Further network enrichment analysis demonstrated that differential lipid metabolism was regulated by klf4 and hist1h2ba, and were validated by RT-qPCR., Conclusion: In our study, the chemical profile of Bhjm was clarified. Moreover, the GMD repair effect and the mechanism of Bhjm and EA was comprehensively analyzed for the first time, involving inflammation and lipid metabolism. Collectively, these findings will be significantly helpful for deeply exploring the clinical application value of Bhjm., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interest., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Curcumin is a natural phenol found in the rhizome of Curcuma longa. It has been studied to treat several human carcinomas, such as melanomas and breast, head and neck, prostate, and ovary cancers. Here, we develop and validate a method for recovering curcumin from the skin layers and mucosa and selectively quantifying it, aiming to support permeation studies in developing topical formulations containing the natural compound. Recovery of curcumin from the stratum corneum, remaining skin, and mucosa was performed using ethanol, DMSO/ethanol, and DMSO, respectively, under mild stirring for specific periods. The separation of curcumin from the other curcuminoids, skin, and mucosa interferents was obtained using a C 18 column as a stationary phase. The mobile phase was composed of pH 3.0 phosphoric acid at 1.0 mmol/L and acetonitrile (47:53, v/v), which flowed at 1 mL min -1 . UV-Vis detection of curcumin was at 424 nm. The chromatographic method was selective, linear (r > 0.999), with a regression curve in the concentration range from 1.0 to 30.0 μg mL -1 , robust, precise, and accurate, with curcumin recovery rates higher than 95 ± 7 % from the mucosa, 82 ± 2 % from the stratum corneum, and 65 ± 10 % from the remaining skin. Finally, the method was successfully used in a skin permeation test performed with porcine skin and mucosa. The validated method is, therefore, suitable for the recovery and quantification of curcumin from the skin layers and mucosa, favoring the development of new topical formulations destined for these sites of administration., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Strains LMG 7974 T and LMG 8286 T represent single, novel Campylobacter lineages with Campylobacter pinnipediorum and Campylobacter mucosalis as nearest phylogenomic neighbours, respectively. The results of average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) analyses of LMG 7974 T , LMG 8286 T and type strains of species of the genus Campylobacter confirmed that these strains represent novel species of the genus Campylobacter . The 16S rRNA gene sequences of both strains showed highest identity towards C. mucosalis (97.84 and 98.74 %, respectively). Strains LMG 7974 T and LMG 8286 T shared 72.5 and 73.7% ANI, respectively, with their nearest phylogenomic neighbours and less than 21 % dDDH. The draft genome sizes of LMG 7974 T and LMG 8286 T are 1 945429 bp and 1 708214 bp in length with percentage DNA G+C contents of 33.8 and 37.2 %, respectively. Anomalous biochemical characteristics and low MALDI-TOF mass spectrometry log scores supported their designation as representing novel species of the genus Campylobacte . We therefore propose to classify strain LMG 7974 T (=CCUG 20705 T ) as the type strain of the novel species Campylobacter majalis sp. nov. and strain LMG 8286 T (=CCUG 24193 T , NCTC 11879 T ) as the type strain of the novel species Campylobacter suis sp. nov.

Introduction: Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) resulted in a worldwide pandemic, due to its great capacity to invade the human body. Previous studies have shown that the primary route of invasion of this virus is the human respiratory tract via the co-expression of ACE2 receptor and TMPRSS2, a serine protease on the cellular surface. Interestingly, this condition is present not only on the respiratory epithelium but on the conjunctival mucosa, as well. Thus, we hypothesized that SARS-CoV-2 is present on the conjunctival mucosa., Aim: To prove that SARS-CoV-2 can be detected in the conjunctiva., Methods: Previously nasopharyngeal swab-sample based real-time polymerase chain reaction (PCR) positive COVID-19 infected patients were selected at the COVID Care Centers of Semmelweis University, Budapest, Hungary. The study was approved by the ethical committee of Semmelweis University. During their recovery, both nasopharyngeal and conjunctival swab-samples were taken and PCR method was used to detect the presence of SARS-CoV-2 RNA. Appropriate statistical analysis was performed., Results: The study population consisted of 97 patients, 49 females (50.5%) and 48 males (49.5%), with a mean age of 67.2 ± 11.9 years. During recovery, with nasopharyngeal swabs, the PCR test was positive in 55 cases (56.70%), whereas with conjunctival swabs it was positive in 8 cases (8.25%). Both tests were positive in 5 cases (5.15%). In some patients, ocular symptoms were observed as well. The rest of the patients (29 cases) had negative nasopharyngeal PCR tests during recovery., Conclusions: Although only in few cases, the data of the present study provides a proof of concept that SARS-CoV-2 can be present on the conjunctival mucosa even in nasopharyngeal negative patients, a finding, which can have clinical importance. Also, on the basis of these findings one can hypothesize that - in addition to the respiratory tract - the conjunctiva can be an entrance route for SARS-CoV-2 to the human body. Thus, in high-risk conditions, in addition to covering the mouth and nose with mask, the protection of the eyes is also strongly recommended.

Heated tobacco products (HTP) are novel nicotine delivery products with limited toxicological data. HTP uses heating instead of combustion to generate aerosol (HTP-smoke). Physiologically relevant human bronchial and alveolar lung mucosa models developed at air-liquid interface were exposed to HTP-smoke to assess broad toxicological response (n = 6-7; ISO puffing regimen; compared to sham; non-parametric statistical analysis; significance: p < 0.05). Elevated levels of total cellular reactive oxygen species, stress responsive nuclear factor kappa-B, and DNA damage markers [8-hydroxy-2'-deoxyguanosine, phosphorylated histone H2AX, cleaved poly-(ADP-Ribose) polymerase] were detected in HTP-smoke exposed bronchial and/or alveolar models. RNA sequencing detected differential regulation of 724 genes in the bronchial- and 121 genes in the alveolar model following HTP-smoke exposure (cut off: p ≤ 0.01; fold change: ≥ 2). Common enriched pathways included estrogen biosynthesis, ferroptosis, superoxide radical degradation, xenobiotics, and α-tocopherol degradation. Secreted levels of interleukin (IL)1ꞵ and IL8 increased in the bronchial model whereas in the alveolar model, interferon-γ and IL4 increased and IL13 decreased following HTP-smoke exposure. Increased lipid peroxidation was detected in HTP-smoke exposed bronchial and alveolar models which was inhibited by ferrostatin-1. The findings form a basis to perform independent risk assessment studies on different flavours of HTP using different puffing topography and corresponding chemical characterization., (© 2022. The Author(s).)

In sexual assault cases, it can be challenging to identify the type of body fluids/ cell types present in a crime scene sample, especially the origin of epithelial cells. Therefore, more labs are applying mRNA body fluid analysis for saliva, skin and vaginal mucosa markers. To address activity level propositions, it is necessary to assign probabilities of transfer, persistence, prevalence and recovery of DNA and mRNA markers. In this study we analysed 158 samples (fingernail swabs, penile swabs and boxershorts) from 12 couples collected at different time points post intimate contact and after non-intimate contact in order to detect DNA from the person of interest (POI) and mRNA vaginal mucosa markers. Samples were DNA and RNA co-extracted and analysed with PowerPlex®Fusion 6C System and 19-plex mRNA primer mix respectively, using Endpoint PCR and the CE platform. Vaginal mucosa was detected up to 36 h post intimate contact, but also detected in one non-intimate contact sample. In 94% of intimate contact and 50 % of non-intimate contact samples the DNA results support the proposition that POI is the donor (LR ≥ 10,000). There was a strong association between the detection of vaginal mucosa and the average RFU value of the POI. The data were used to instantiate a comprehensive Bayesian network to evaluate the evidence at activity level, given alternate propositions conditioned upon indirect or direct transfer events. It is shown that the value of the evidence is mainly affected by the high DNA quantity (measured as mean RFU) that is recovered from the POI. The detection of vaginal mucosa had low impact upon the resultant likelihood ratio., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Preclinical studies have shown that the induction of secretory IgA (sIgA) in mucosa and neutralizing antibodies (NAbs) in sera is essential for designing vaccines that can effectively block the transmission of HIV-1. We previously showed that a vaccine consisting of bacterium-like particles (BLPs) displaying Protan-gp120AE-MTQ (PAM) could induce mucosal immune responses through intranasal (IN) immunization in mice and NAbs through intramuscular (IM) immunization in guinea pigs. Here, we evaluated the ability of this vaccine BLP-PAM to elicit HIV-1-specific mucosal and systemic immune responses through IN and IM immunization combination strategies in rhesus macaques. First, the morphology, antigenicity and epitope accessibility of the vaccine were analysed by transmission electron microscopy, bio-layer interferometry and ELISA. In BLP-PAM-immunized macaques, HIV-1-specific sIgA were rapidly induced through IN immunization in situ and distant mucosal sites, although the immune responses are relatively weak. Furthermore, the HIV-1-specific IgG and IgA antibody levels in mucosal secretions were enhanced and maintained, while production of serum NAbs against heterologous HIV-1 tier 1 and 2 pseudoviruses was elicited after IM boost. Additionally, situ mucosal responses and systemic T cell immune responses were improved by rAd2-gp120AE boost immunization via the IN and IM routes. These results suggested that BLP-based delivery in combination with the IN and IM immunization approach represents a potential vaccine strategy against HIV-1., (© 2022 The Authors. Microbial Biotechnology published by Society for Applied Microbiology and John Wiley & Sons Ltd.)

To detect the expression of galectin-13 in allergic diseases and provide a new way for the diagnosis and treatment of allergic diseases. A retrospective analysis method was used to screen 216 patients with allergic diseases with house dust mites or aspergillus as allergens who visited the Department of Allergy and Department of Respiratory of Tongji Hospital attached Tongji Medical College, Huazhong University of Science and Technology from March 2018 to May 2021. These allergic diseases included allergic asthma, allergic bronchopulmonary aspergillosis, allergic rhinitis, allergic conjunctivitis, atopic dermatitis, allergic urticaria. 25 subjects without underlying diseases were selected as healthy controls. The galectin-13 content in serum in each group were detected, and the Pearson correlation was used to determine the correlation between the galectin-13 content in serum in each group and blood eosinophil count, blood specific IgE, the score scale of allergic disease. The expression of Galectin-13 was increased in allergic asthma group (71.44±39.44) pg/ml, allergic bronchopulmonary aspergillosis group (100.10±47.62) pg/ml, allergic rhinitis group (54.11±24.81) pg/ml and dermatitis group (44.12±19.51) pg/ml. The expression of galectin-13 was not significantly increased in allergic urticaria group (32.75±10.29) pg/ml and the allergic conjunctivitis group (30.55±9.87) pg/ml. The galectin-13 content in serum, was positively correlated with blood eosinophil count( r s =0.54, P <0.001) and house dust mite specific IgE ( r s =0.51, P <0.001) in allergic asthma group, and was positively correlated with blood eosinophil count( r s =0.63, P =0.025) and aspergillus fumigatus specific IgE ( r s =0.58, P =0.046) in allergic bronchopulmonary aspergillosis group. It was positively correlated with blood eosinophil count ( r s =0.52, P =0.000 2) and house dust mite specific IgE ( r s =0.41, P =0.005) in allergic rhinitis group. In allergic conjunctivitis group, the expression of galectin-13 was positively correlated with conjunctivitis symptom score ( r s =0.47, P =0.048). In atopic dermatitis group, the expression of galectin-13 was positively correlated with blood eosinophil count ( r s =0.58, P <0.001) and house dust mite specificity IgE ( r s =0.47, P =0.002). In allergic urticaria group, the expression of galectin-13 was not significantly correlated with blood eosinophil count or house dust mite specific IgE. Galectin-13 may be related to the occurrence and progress of allergic diseases and may be involved in the occurrence of eosinophilic inflammation.

Background: Mucous membrane pemphigoid (MMP) is an autoimmune disease characterized by scarring lesions at mucosal sites. Although the pathogenic role of specific IgG and/or IgA has been already demonstrated and the detection of these immunoglobulins is a criterion in the diagnosis of MMP, little is known about IgE role in this disease. Therefore, the main purpose of this study was to assess the presence of circulating and tissue bound IgE in patients with MMP and their possible correlations with clinical presentation and disease course., Methods: We conducted a retrospective study on 29 patients affected by MMP, recruited from a single center. Direct and indirect immunofluorescence studies were assessed to analyze the presence of specific IgE directed against the basal membrane zone. For each patient, fluorescence data were compared to clinical features., Results: Linear deposits of C3, IgG and IgA were present in 86.2%, 62% and 37.9% of cases respectively, while IgE linear deposits were detected in 17 out of 29 patients (58.6%) including one case with isolated IgE positivity. Circulating IgE and IgA anti-BMZ were present in 7 (24.1%) and 5 (17.2%) patients, respectively. Both the presence of circulating IgA and of tissue bound IgE deposits correlated with disease activity index (P<0.014)., Conclusions: Our results demonstrated the presence of IgE autoantibodies in MMP, particularly in more severe cases. Thus, IgE detection may represent an additional useful diagnostic tool in this disease.

Nanodiamonds (NDs) are an emerging delivery system with a massive surface area qualifying them for efficient loading with various drugs. However, NDs easily scavenge ions upon mixing with physiological media leading to rapid aggregation. Herein, chitosan was employed to endue steric stabilization to NDs and confer adhesiveness to the particles improving their retention in the urinary bladder. The effect of chitosan molecular weight and pH on the particle size and surface charge of chitosan-coated doxorubicin-loaded NDs (Chi-NDX) was investigated. Selected formula exhibited high drug loading efficiency (>90 %), small particle size (<150 nm), good colloidal stability, acid-favored drug release but limited stability in cell culture media. After further stabilization with TPP or dextran sulfate, selected TPP-treated formula displayed more potent cytotoxic effect compared with free doxorubicin and uncoated nanoparticles, and higher drug retention in ex vivo bovine bladder. Therefore, TPP-Chi-NDX is suggested as a promising system for mucosal anticancer delivery., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Introduction: The majority of new HIV infections occur through mucosal transmission. The availability of readily applicable and accessible platforms for anti-retroviral (ARV) delivery is critical for the prevention of HIV acquisition through sexual transmission in both women and men. There is a compelling need for developing new topical delivery systems that have advantages over the pills, gels and rings, which currently fail to guarantee protection against mucosal viral transmission in vulnerable populations due to lack of user compliance. The silk fibroin (SF) platform offers another option that may be better suited to individual circumstances and preferences to increase efficacy through user compliance. The objective of this study was to test safety and efficacy of SF for anti-HIV drug delivery to mucosal sites and for viral prevention., Methods: We formulated a potent HIV inhibitor Griffithsin (Grft) in a mucoadhesive silk fibroin (SF) drug delivery platform and tested the application in a non-human primate model in vivo and a pre-clinical human cervical and colorectal tissue explant model. Both vaginal and rectal compartments were assessed in rhesus macaques (Mucaca mulatta) that received SF (n = 4), no SF (n = 7) and SF-Grft (n = 11). In this study, we evaluated the composition of local microbiota, inflammatory cytokine production, histopathological changes in the vaginal and rectal compartments and mucosal protection after ex vivo SHIV challenge., Results: Effective Grft release and retention in mucosal tissues from the SF-Grft platform resulted in protection against HIV in human cervical and colorectal tissue as well as against SHIV challenge in both rhesus macaque vaginal and rectal tissues. Mucoadhesion of SF-Grft inserts did not cause any inflammatory responses or changes in local microbiota., Conclusions: We demonstrated that in vivo delivery of SF-Grft in rhesus macaques fully protects against SHIV challenge ex vivo after two hours of application and is safe to use in both the vaginal and rectal compartments. Our study provides support for the development of silk fibroin as a highly promising, user-friendly HIV prevention modality to address the global disparity in HIV infection., (© 2020 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

Pseudocarcinomatous hyperplasia (PCH) is a benign reactive epithelial proliferation that may be associated to lymphomas of the skin or external mucous membranes. We present a case of single lesion mycosis fungoides (Woringer-Kollop's reticulosis pagetoid) associated with PCH that was initially misdiagnosed as squamous cell carcinoma (SCC) and review all PubMed-indexed previously reported cases on lymphomas of the skin or external mucous membranes associated to PCH, SCC, and keratoacanthomas. Including our own case, we collected data of 114 cases of cutaneous or mucosal lymphoproliferative disorders associated to PCH, 3 cases associated to SCC, and other 3 cases associated to keratoacanthomas. All cases were tabulated to the following parameters whenever data was available: sex, age, previous medical conditions, number of lesions (single × multiple), site of involvement (mucosa, skin or both), clinical impression, initial equivocal histopathologic diagnosis, final diagnosis, keratinocytic atypia (presence × absence), lymphocytic atypia (presence × absence), CD30-status, and treatment.

Tumors located in the oral mucosa are challenging to treat since surgery can lead to aesthetic, speech, and salivation problems, radiotherapy alone is often ineffective, and systemic chemotherapy brings meaningful side effects to the patient. Here, we proposed to develop mucoadhesive chitosan nanoparticles entrapping the chemotherapeutic oxaliplatin (OXPt) and to evaluate ex vivo its penetration in porcine mucosa under both passive and iontophoretic topical treatments. OXPt-loaded chitosan nanoparticles presented a small hydrodynamic size (188 ± 20 nm), narrow distribution (PDI of 0.28 ± 0.02) and positive zeta potential (+44.8 ± 2.8 mV). These nanoparticles provided a "burst effect" on drug release followed by a longer-term controlled release. When applied to the oral mucosa, the chitosan nanoparticles increased 3-fold drug penetration, and this rate was maintained even when the mucosa was "washed" with a buffer to mimic salivation. Iontophoresis doubled the amount of OXPt transported to the mucosa. These amounts exceeded the dose required to cause cell death of an oral tumor cell line. Besides, chitosan nanoparticles increased the rate of cells that entered into apoptosis. In summary, this study points to the feasibility of topical therapy with chitosan nanoparticles, potentialized by the application of iontophoresis, to treat oral tumors., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Alcoholic-alkaline treatment (AAT) is a physical modification method for the production of granular cold water swelling starch and should be optimized for each starch source. The main objective of this research was to investigate physical and mucoadhesive properties of tapioca starch (TS) modified by different AATs. Improvement of cold-water absorption, solubility, rheological properties at low temperatures, clarity, freeze-thaw stability, and mucoadhesion was positively correlated with the alkali amount and reaction temperature and negatively correlated with ethanol content. Morphological studies demonstrated different degrees of swelling, birefringence loss, and surface wrinkling of granules depending on modification degree. Starch pastes, modified in a higher degree, showed a change from rheopexy to thixotropy and from translucency to turbidity over time. The highest quality along with maintaining granular integrity was obtained by treating starch (10 g) with 30 g alkaline solution (2.5 M) and 110 g aqueous ethanol (40%) at 25 °C. The characteristics of this sample were higher than those of corn counterpart except for viscosity, consistency, and freeze-thaw stability and were almost similar to those of thermally gelatinized TS (TGTS). Therefore, this AA-modified TS can be an alternative for TGTS in instant and heat-sensitive foods and delivery of bioactives as a mucoadhesive polymer., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The design of mucoadhesive drug delivery systems (DDS) based on polysaccharides at nanoscale or microscale is a relevant technological strategy for the mucosal delivery of several drugs. Findings about the potential mucoadhesive ability of these materials and the mechanisms that drive such interactions represents an important advance for the rational modulation of these properties, according to specific uses. The potential mucoadhesive abilities of gellan gum (GG) and retrograded starch (RS) were investigated at pH 1.2 and 6.8, which were considered biorrelevant for the gastrointestinal tract (GIT). The effects of these polysaccharides on the MUC rheology were also addressed. Rheological studies revealed high MUC-GG interactions at both pH values (1.2 and 6.8), expressing a high mucoadhesive ability, mainly in acidic media. MUC-GG interactions were driven, mainly, by hydrogen bonds. At an acidic pH, significant changes occurred in the MUC arrangements due to the strong MUC-GG interactions, as corroborated by scanning electron microscopy (SEM). The rheological behavior of MUC-RS indicated poor interactions between them and MUC arrangements were more preserved as evidenced by SEM. The results of this work indicated that the mixing of GG and RS can be a promising strategy to modulate mucoadhesiveness of DDS, according to specific therapeutic needs., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Heterobothrium okamotoi, a monogenean gill parasite, exhibits high host specificity for the tiger puffer, Takifugu rubripes, and it has been experimentally verified that the parasite cannot colonize either closely related species such as the grass puffer Takifugu niphobles or distantly related fish such as the red seabream Pagrus major. Previously, we demonstrated in T. rubripes that immunoglobulin M (IgM) with d-mannose affinity induced deciliation of the oncomiracidia, the first step of parasitism, indicating that the parasite utilizes the molecule as a receptor for infection. In the present study, we purified mannose-specific IgM from 2 nonhost species, T. niphobles and P. major, by affinity and gel-filtration chromatography techniques and compared their deciliation-inducing activity against H. okamotoi oncomiracidia. The IgM of the former showed activity, whereas the latter had no effect, suggesting that in addition to d-mannose-binding ability, the crystallizable fragment domain of IgM, which is not part of the antigen-binding domain, plays an important role in host recognition by the oncomiracidia, such as direct binding to the parasites. It also suggests that the host specificity of H. okamotoi is relatively low upon initial recognition, and the specificity is established by exclusion in nonhosts during a later stage., (© American Society of Parasitologists 2020.)

The impact of abnormalities in the vascular bed of the external genitalia and vagina on female sexuality is not well defined because of some methodological difficulties in correctly assessing vascular changes of genitalia in women. Transmucosal oxygen tension (TmPO2) represents a precise measure of oxygen partial pressure at the clitoris surface and is expression of clitoral tissue perfusion. Aim of the study was to correlate TmPO2 with female sexual dysfunction (FSD) in healthy women in order to evaluate the impact of clitoral vascularization on female sexual health. Twenty-seven healthy, heterosexual, and sexually active women of reproductive age (mean age: 31.18 ± 4.71) were enrolled in the study. TmPO2 was assessed in every woman. In addition, all the women filled out the Female sexual function index (FSFI). After adjustment for some covariates (age, BMI, and smoking), TmPO2 significantly correlated with FSFI total score (r = 0.4261; p = 0.0379) and with arousal (r = 0.3239; p = 0.0390), lubrication (r = 0.4345; p = 0.0339), orgasm (r = 0.4092; p = 0.0471), and satisfaction (r = 0.4456; p = 0.0291) scores. In addition, TmPO2 was significantly lower in the FSD than in the NO FSD group (28.4 ± 14.5 versus 48.1 ± 25.1 mmHg; p = 0.0416). This study first shows that in healthy women of reproductive age clitoral tissue perfusion, as assessed by TmPO2, correlates very well with FSD and in particular with arousal, lubrication, orgasm, and satisfaction. Further studies should confirm our data and test TmPO2 as potential predictor for cardiovascular disease and metabolic conditions in women.

Oral delivery of amphotericin B (AmpB) is desirable because it provides a more patient-friendly mode of administration compared to the current delivery approach akin with the marketed AmpB formulations. The goal of the study was to investigate the pharmacokinetics and tissue distribution of orally administered chitosan-coated AmpB-loaded nanostructured lipid carriers (ChiAmpB NLC) administered to Sprague Dawley rats at a dose of 15 mg/kg. Orally administered ChiAmpB NLC resulted in a two-fold increase in the area under the curve (AUC 0-∞ ) compared to the uncoated AmpB NLC and marketed Amphotret ® . This enhanced bioavailability of AmpB suggests prolonged transit and retention of ChiAmpB NLC within the small intestine through mucoadhesion and subsequent absorption by the lymphatic pathway. The results show that mean absorption and residence times (MAT & MRT) were significantly higher from ChiAmpB NLC compared to the other two formulations, attesting to the mucoadhesive effect. The ChiAmpB NLC presented a lower nephrotic accumulation with preferential deposition in liver and spleen. Thus, the limitations of current marketed IV formulations of AmpB are potentially addressed with the ChiAmpB NLC in addition to utilizing this approach for targeting internal organs in visceral leishmaniasis.

In this study, insulin-loaded nanoparticles (NPs) were prepared via self-gelation method using chitosan and aqueous soluble snail mucin as natural polymers. Herein, mucins were ionically interacted with chitosan at different concentrations to obtained insulin-loaded NPs, labelled as A1 (1:1) (i.e., chitosan 2 % w/v + mucin 2 % w/v) and A2 (2:1) (chitosan 4 % w/v + mucin 2 % w/v), using poloxamer and poly vinyl alcohol as solid surfactant. Such formulation was selected to provide the necessary dynamics for the formation of the nanoparticles while maintaining the surface properties that will favor the encapsulation of insulin. Each system was characterized in terms of their particle size distribution, morphology, zeta potential, and polydispersity index. In vitro release of insulin was evaluated in acidic solution (pH 1.2) and phosphate buffer solution (pH 7.4), and the hypoglycaemic activity was evaluated in diabetes rats. The prepared insulin-loaded NPs displayed particles with relatively smooth surfaces and an average particle size of 479.6 and 504.1 nm for A1 and A2, respectively. Zeta potential and polydispersity index, ranged from 22.1 to 31.2 mV and 0.155-0.185, respectively. The encapsulating efficiency for the systems A1 and A2 were 88.6 and 92.5, respectively, and a self-sustained release of encapsulated insulin was observed for over a period of 8 h. In vivo studies revealed a pronounced hypoglycaemic effect in diabetic rats after peroral administration of the insulin-loaded NPs compared to the effect caused by free oral insulin solution. In addition, both the pharmacokinetic and toxicity results showed low plasma clearance of insulin and no signs of toxicity on the liver enzyme and cell viability, which suggested good biocompatibility of the NPs formulations. Overall, the formation of NPs of insulin with chitosan and snail mucin represents a potentially safe and promising approach to protect insulin and enhance its peroral delivery., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The fates and detrimental effects of particles entering the body have gained increasingly notable attention worldwide because of the burgeoning applications of various particles and wide existence of ambient particulate matter. Studies on the interaction of particles with biological interfaces demonstrate the potential risks and hazards to the health of living organisms. This review aims to provide a systematic overview of the interaction between particles and typical biological interfaces, with an emphasis on the effects of particle properties and microenvironment, and the potential adverse results arising from these interactions. First, we describe the major entry routes of particles into the human body to understand the main exposure pathways and the fates and impacts of particles. Different behaviors of particles interacting with mucosae and cell membranes are then reviewed. Finally, the knowledge gaps are identified and the long-term development of interaction research is proposed., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Oral administration of nanoparticles is extremely limited due to the two processes of mucus permeation and epithelial absorption, which requires completely opposite surface properties of the nanocarriers. To tackle the contradiction, we developed a rational strategy to modify the surface of mesoporous carbon nanoparticles with chitosan concealed by a hydrophilic N-(2-hydroxypropyl) methacrylamide copolymer (pHPMA) layer. Probucol (PB) with the low poor permeability and solubility was loaded in optimal nanocarriers to realize the high loading efficacy and controlled release. The pHPMA polymer is a hydrophilic "mucus-inert" material, which could be dissociable from the surface of nanoparticles in the mucus, thus promoting their mucus permeation and causing exposure of chitosan in transepithelial transport. The swelling effect of chitosan under acidic conditions allowed regulation of PB release behavior. In conclusion, the mucus-permeable nanocarrier could effectively overcome multiple gastrointestinal absorption barriers and the oral bioavailability of PB-loaded HCMCN was 2.76-fold that of commercial preparation., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

This study evaluates the effects of different gum extraction methods on the mucoadhesive strengths of Abelmoschus esculentus (AE) and Irvingia gabonensis (IG) gums and the release of vaccine antigen in vaccine-gum formulations. AE and IG gums were extracted employing previously documented methods with acetone or sodium chloride (NaCl) and either oven-dried or freeze-dried. Gum extracts were analyzed for mucoadhesive strengths using a modified rotational cylinder method on animal mucosa. The time taken to detach from the mucosa was taken as the Peak Adhesion Time (PAT). The gum extracts were charged with Peste des petits ruminant vaccine and the antigen release was evaluated using agar gel immunodiffusion technique. The means of the PATS were analyzed using Mann-whitney t-test at p < .05. The NaCl extracted and freeze-dried IG gum showed sustained mean PATs of 1766 ± 73 s; 2116 ± 101 s; 7044 ± 117 s, while the oven-dried IG gum and both AE gums showed short-lived average PATs. Vaccine-gum formulations of IG at ratios 2:1, 1:1 & 1:2 had strong positive reactions while only that of AE at 2:1 showed a strong positive reaction. This study shows that NaCl extracted and freeze-dried IG gum has immunomodulatory potential for mucoadhesive vaccine delivery in ruminants.

The evolution of drug resistance of Candida species to conventional antifungal agents has been a major medical challenge worldwide; attempt to use the potential antifungal agents with appropriate therapy efficacy and minimum effects is considerably growing. This study was conducted to evaluate the use of nanogel as a nanocarrier for pharmaceutical application of farnesol. The nanogels were synthetized using alginate (AL) and chitosan (CS) polymers containing 300 µM of farnesol in the nano-range 42-70 nm size. In vitro release studies indicated that release of farnesol from CS and AL nanogels was as 58% and 37%, respectively. Chitosan nanogel showed more in inhibitory zone as compared to AL nanogel (9 mm). Also, cytotoxicity assay showed no significant difference between control and treatment groups (p>.05). Finally, the effect of nanogels on genes expression of HWP1, SAP6 and Rim101 in Candida albicans ATCC10231 was assessed using real-time polymerase chain reaction (PCR). Expression of HWP1 and SAP6 genes in C. albicans treated with CS nanogel was significantly decreased (p<.01). In general, the obtained finding showed that, CS nanogel contains farnesol with proper antifungal activity and as a new approach used in pharmaceutical applications against C. albicans; however, more studies in vitro and in vivo are needed in the future.

Parkinson's disease is the second most common neurodegenerative disorder after Alzheimer's disease and is estimated to affect approximately 1-4% of individuals aged over 60 years old. Although considerable efforts have been invested into developing disease-modifying therapies for Parkinson's disease, such efforts have been confounded by the difficulty in accurately diagnosing Parkinson's disease during life to enable accurate patient stratification for clinical trialling of candidate therapeutics. Therefore, the search for effective biomarkers that can be accurately evaluated during life with non-invasive means is a pressing issue in the field. Since the discovery of α-synuclein (α-syn) as a protein linked to a familial form of Parkinson's disease, later identified as the major protein component of the neuropathological hallmark of idiopathic Parkinson's disease, considerable interest has focused on this protein and its distinct conformers. We describe here the progress that has been made in the area of Parkinson's disease biomarker discovery with a focus on α-synuclein. In particular, we highlight the novel assays that have been employed and the increasing complexity in evaluating α-synuclein with regard to the considerable diversity of conformers that exist in the biofluids and peripheral tissues under disease conditions. "This article is part of the Special Issue Synuclein.", (© 2019 International Society for Neurochemistry.)

This study aims to obtain an inhalation powder with meaningful aerodynamic and safety profiles for the lung delivery of losartan (LS). For this, the capacity of self-assembly of chitosan (CS) and dextran sulfate (DS) to form CS/DS microplex (MC), incorporating high payload of hydrophilic LS was harnessed. Dry powder inhaler (LS-MC-DPI), prepared via spray drying of the best achieved LS-MC, was proposed to impart precise engineered inhalation characteristics. Micrometric robust CS/DS MC was revealed to offer the opportunity to heighten LS encapsulation, accounting for ~75%. LS-MC-DPI was successfully developed with high yield, flowability, respirable aerodynamic size and morphology which formed swellable and mucoadhesive network, facilitating intra-pulmonary delivery. Moreover, sustained release pattern, augmented deep lung deposition and safe histological profile were realized. Overall, the newly developed LS-MC DPI shows promises as an inhalation system. The aerodynamic performance and safety of LS-MC-DPI verify its suitability for further in vivo lung therapeutics., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Fungal keratitis (FK) is treated by topical natamycin (Nat) which is an effective antifungal agent. However, it has numerous therapeutic limitations i.e. toxicity, tolerance, need of frequent dosing and patient incompliance. The aim of the present study was to develop Nat loaded trimethyl chitosan (TMC) coated mucoadhesive cationic niosomes (Muc-Cat-Nios) for prolonged and effective delivery to eyes. Niosomes were prepared using thin film hydration method and optimized using a Box-Behnken design (BBD) with the help of Design-Expert® Software. Three independent variables were considered: amount of Span 60 (X 1 ), amount of Cholesterol [Chol(X 2 )] and TMC concentration (X 3 ). The encapsulation efficiency (R1: EE%), vesicle size (R2: VS) and Zeta potential (R3: ZP) were selected as dependent variables or responses. The optimized Nios displayed spherical shape, 1034.14 nm vesicle size and 81.76% EE. Nat loaded niosomes were incubated with TMC to get mucoadhesive cationic vesicular system. Uncoated and TMC coated niosomes were characterized for mucoadhesive properties, in vitro drug release, rheological behaviour, and ex vivo permeation studies. Cationic Nios showed greater mucoadhesive potential that provided drug release for a long period of time. The promising outcomes suggest that natamycin delivery using cationic mucoadhesive niosomes could be employed for the effective treatment of fungal keratitis., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Breastfeeding is nowadays known to be one of the most critical factors contributing to the development of an efficient immune system. In the last decade, a consistent number of pieces of evidence demonstrated the relationship between a healthy organism and its gut microbiota. However, this link is still not fully understood and requires further investigation. We recently adopted a murine model to describe the impact of either maternal milk or parental genetic background, on the composition of the gut microbial population in the first weeks of life. A metaproteomic approach to such complex environments is a big challenge that requires a strong effort in both data production and analysis, including the set-up of dedicated multitasking bioinformatics pipelines. Herein we present an LC-MS/MS based investigation to monitor mouse gut microbiota in the early life, aiming at characterizing its functions and metabolic activities together with a taxonomic description in terms of operational taxonomic units. We provided a quantitative evaluation of bacterial metaproteins, taking into account differential expression results in relation to the functional and taxonomic classification, particularly with proteins from orthologues groups. This allowed the reduction of the bias arising from the presence of a high number of shared peptides, and proteins, among different bacterial species. We also focused on host mucosal proteome and its modulation, according to different microbiota composition. SIGNIFICANCE: This paper would represent a reference work for investigations on gut microbiota in early life, from both a microbiological and a functional proteomic point of view. We focused on the shaping of the mouse gut microbiota in dependence on the feeding modality, defining a reliable taxonomic description, highlighting some functional characteristics of the microbial community, and performing a first quantitative evaluation by data independent analysis in metaproteomics., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Intravesical mucoadhesive self-emulsifying drug delivery system (SEDDS) have been developed via synthesis and incorporation of S-protected chitosan CS-MNA into SEDDS. N-acetyl cysteine-6-mercaptonicotinamide (NAC-6-MNA) was synthetized via disulphide exchange reaction between N-acetyl cysteine and 6-mercaptonicotinamide dimer. NAC-6-MNA was attached to chitosan (CS) via carbodiimide mediated amide bond formation. The S-protected chitosan (CS-MNA) and chitosan (CS) were complexed with sodium dodecyl sulfate (CS-SDS and CS-MNA-SDS) and incorporated in SEDDS at a concentration of 1% (m/m). SEDDS, SEDDS-CS-SDS and SEDDS-CS-MNA-SDS were characterized regarding size and zeta potential. 6-MNA release from SEDDS-CS-MNA-SDS in presence of glutathione was evaluated. Mucoadhesive properties of these novel formulations were assessed via rheology measurements and residence time evaluation on porcine bladder. Cytotoxicity of formulations was determined on porcine bladder. S-protected chitosan displayed 465.42 ± 75.64 µmol of NAC-6-MNA per gram of polymer. SEDDS and SEDDS-CS-SDS and SEDDS-CS-MNA-SDS displayed a size of 22.5 ± 0.9, 37.4 ± 0.1 and 98.5 ± 5.7 nm at a concentration of 20% (m/v) in simulated urine pH 6.2, and a zeta potential of -5.1 ± 0.2, -1.6 ± 0.1 and -1.4 ± 0.2 mV at a concentration of 1% (m/v) in water at pH 6, respectively. 80% of MNA was released from SEDDS-CS-MNA-SDS in presence of glutathione. Viscosity of SEDDS-CS-SDS/mucus and SEDDS-CS-MNA-SDS/mucus was 6- and 18-fold higher than SEDDS/mucus after 90 min incubation. 2.6%, 5.8% and 14% of SEDDS, SEDDS-CS-SDS and SEDDS-CS-MNA-SDS remained on bladder mucosa within 120 min, respectively. No pronounced bladder cytotoxicity was observed in presence of 0.5% (m/v) formulations. According to these results, SEDDS-CS-MNA-SDS might be a promising carrier for intravesical drug administration., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The aim of this study was to synthesize novel polymeric excipients forming mucoadhesive films for treatment of vaginal microbial infections. 2-(2-Amino ethyldisulfanyl) nicotinic acid was conjugated with gellan gum via amide bond formation. The structure of the resulting S-protected gellan gum was confirmed by 1 H NMR. S-protected gellan gum variants were characterized for thiol content, cytotoxicity, rheological behaviour and film forming capability. Depending on the added amount of AMENA degree of thiolation was 81 ± 13 (S-GG 81) and 174 ± 16 (S-GG 174) μmol/g, respectively. Vaginal films were casted from S-protected gellan gum variants and studied for adherence to vaginal mucosa, drug release and antimicrobial activity. S-protected gellan gum remained biocompatible showing >87% cell viability. S-GG 81 and S-GG 174 exhibited 1.84- and 4.3-fold increased dynamic viscosity in porcine mucus in comparison to unmodified gellan gum, respectively. Compared to gellan gum films, thiol functionalized gellan gum films showed 3-fold improved adhesion on mucosal surface over a period of 3 h along with significant antimicrobial activity. Moreover, S-protected gellan gum provided a sustained release of metronidazole. According to these results, S-protected gellan gum proved to be a promising novel excipient for casting vaginal films, exhibiting strongly improved mucoadhesive and antimicrobial properties., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Oral drug delivery technology is mainly provided in the form of solid oral dosage forms (SODF) that have to be swallowed intact and move throughout the oro-esophageal system to release the drug content in the stomach or intestine. As there is growing evidence for an increasing prevalence of impaired swallowing functions in certain diseases, multimorbidity and advanced age, predictive in vitro methods for the oro-esophageal gliding behavior of SODF would be very useful. The gliding performance of different SODF polymer films was investigated across an artificial mucous layer using a versatile in vitro gliding system. In a first phase, the system measures the force required to move the polymer surface when placed in contact with the mucin layer and, in a second phase, the resistance behavior over a defined length. The obtained results showed that comprehensive gliding profiles could be obtained depending on the polymer film tested. The carnauba wax and PEG coatings required lower gliding peak forces and showed poor gliding resistance, which is indicative of free gliding capacity. In contrast, HPMC, PVP and gelatin coatings required higher gliding forces and exhibited greater resistance due to an adhesive interaction with the artificial mucous layer. The obtained profiles correlate with prior in vitro data during polymer gliding evaluations on mucosal membranes., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Eudragit® E PO (EPO) is a terpolymer based on N,N-dimethylaminoethyl methacrylate with methylmethacrylate and butylmethacrylate, produced by Evonik Industries AG as a pharmaceutical excipient. In this work, EPO was chemically modified through reaction with acryloyl chloride. The successful modification of EPO was confirmed by FTIR, NMR-spectroscopy, elemental and thermal analysis. The degree of acrylation was determined by permanganatometric titration. The slug mucosal irritation test was used to demonstrate non-irritant nature of EPO and its acrylated derivatives (AEPO). The mucoadhesive properties of EPO and AEPO were evaluated using freshly excised sheep nasal mucosa and it was demonstrated that acrylated polymers facilitated greater retention of sodium fluorescein on mucosal surfaces compared to solution mixture of this dye solution with EPO as well as free dye., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Binding of small molecules to mucus membranes in the body has an important role in human health, as it can affect the diffusivity and activity of any molecule that acts in a mucosal environment. The binding of drugs and of toxins and signaling molecules from mucosal pathogens is of particular clinical interest. Despite the importance of mucus-small molecule binding, there is a lack of data revealing the precise chemical features of small molecules that lead to mucus binding. We developed a novel equilibrium dialysis assay to measure the binding of libraries of small molecules to mucin and other mucus components, substantially increasing the throughput of small molecule binding measurements. We validated the biological relevance of our approach by quantifying binding of the antibiotic colistin to mucin, and showing that this binding was associated with inhibition of colistin's bioactivity. We next used a small molecule microarray to identify 2,4-diaminopyrimidine as a mucin binding motif and confirmed the importance of this motif for mucin binding using equilibrium dialysis. Furthermore, we showed that, for molecules with this motif, binding to mucins and the mucus-associated biopolymers DNA and alginate is modulated by differences in hydrophobicity and charge. Finally, we showed that molecules lacking the motif exhibited different binding trends from those containing the motif. These results open up the prospect of routine testing of small molecule binding to mucus and optimization of drugs for clinically relevant mucus binding properties.

A colorimetric scale has the potential to be very useful as a training tool for students in veterinary training programs. The authors of this report hypothesized that clinically active, graduate level veterinary students would assess mucous membrane color with greater consistency using an image-based system than with traditional word-based techniques. Third- and fourth-year veterinary students were asked to evaluate 10 canine gingival mucosa images and rate them with either an image-based scale designed by the authors or a word-based system. Although the mean absolute deviations from the median values were greater for the word scale (0.22) than for the image scale (0.20) indicating increased variation, mixed model analysis did not demonstrate these differences were significant ( p = .120). Based on this data it is possible that prior image and word-based instruction made it easier for the students to differentiate mucous membrane colors, or that the majority of the students were multimodal learners rather than single-type learners, making previous instruction techniques effective regardless of whether they were visual or read/write based. The authors recommend that future investigators both evaluate previous student instruction and consider administering visual, auditory, read/write, kinesthetic (VARK) tests when investigating potential learning aids in veterinary medicine.

Microbicide pharmacokinetic (PK) studies typically sample drug in luminal fluid, mucosal tissue, and blood. Blood measurements can be conducted most frequently, serially within subjects. Antiretroviral drugs, however, act against HIV in mucosal tissue/cells. We computationally modeled the extent measurements in blood can predict concentrations in tissue, focusing on the antiretroviral drug tenofovir delivered by a vaginal gel. Deterministic PK models input host and product factors and output spatiotemporal drug concentrations in luminal fluid, epithelium, stroma/host cells, and blood. Pharmacodynamic (PD) analysis referenced stroma/host cell concentrations to prophylactic values; summary metrics were time from product insertion to protection (t lag ) and degree of protection (PP max ). Results incorporated host factors characteristic of population variability. Neural nets (NN) linked simulated blood PK metrics (C max , t max , AUC, C 24 ) to mucosal PK/PD metrics. The NNs delivered high-performance mapping of these multiparametric relationships. Given multi-log variability typical of biopsy data for tenofovir and other topical microbicides, results suggest downstream but higher fidelity measurements in blood could help improve determination of PK and create inferences about PD. Analysis here is for a tenofovir gel, but this approach offers promise for application to other microbicide modalities and to topical drug delivery to vaginal mucosa more generally.

Background: Several studies suggested that abnormalities in tissue perfusion of external genitalia and vagina can lead to female sexual dysfunctions (FSDs) and can be associated to metabolic and cardiovascular risk factors. However, there are some technical difficulties in assessing these abnormalities. The measurement of oxygen partial pressure is a noninvasive method to measure oxygen partial pressure (pO 2 ) at the skin surface to assess tissue perfusion. The aim of this study was to evaluate whether transmucosal oxygen tension (TmPO 2 ) can be measured at the mucosal surface of clitoris and whether the measurements are reliable., Methods: TmPO 2 was measured in six young healthy women by using a device to measure transcutaneous pO 2 on the skin and by choosing a small sensor, usually used for newborns. The identical procedure for the detection of pO 2 at the skin surface was used., Results: The mean value of TmPO 2 was 42.3 mmHg (range: 24.1-53.4 mmHg). All the trend curves of the TmPO 2 showed the same behavior: after a stabilization time, there was a stable pO 2 (plateau phase) that corresponds to the TmPO 2 of the clitoris. These curves had a similar trend to those recorded at the skin surface., Conclusions: TmPO 2 can be easily measured at the mucosal surface of clitoris. Large epidemiological studies in healthy and unhealthy women and in women with FSD are needed to establish both the normal range of TmPO 2 and the meaning that different values of TmPO 2 can have on sexual and general health of the women.

The current study was aimed to develop extended release (ER) pellets formulations containing zaltoprofen as a model drug and cross-linked starch-κ-carrageenan (Sκ-C) hydrogel composite as a binder and extended release polymer. The Sκ-C cross-linked hydrogel composites were prepared using a 3 2 full factorial design approach and characterized by FTIR, DSC, XRD and SEM analysis. The matrix pellets were prepared by extrusion-spheronization technique and characterized production yield, FTIR, DSC, XRD, SEM, optical microscopy, flow characteristics, mucoadhesiveness, in-vitro dissolution and in-vivo pharmacokinetic parameter. The FTIR interpretation of Sκ-C cross-linked hydrogel composite provides the significant result as a formation of hemiacetal group and keton group of glyoxal is abolished; hence it could be satisfied that Sκ-C cross-linked hydrogel composite was formed. The optimized formulation (Sκ-C2) was contained 4:2 ratio of starch and κ-carrageenan of Sκ-C cross-linked hydrogel composite showed in-vitro drug release up to 99.15 ± 2.20% up to 12h, and mucoadhesion of 94.00 ± 2.00 up to 12 h, respectively and in-vivo parameter were showed decrease in C max and increase in t 1/2 significantly and drug release >12 h. Hence it was concluded that optimized formulation (Sκ-C2) showed acceptable release pattern, hence would be the viable alternative to ER type formulations., (Copyright © 2018. Published by Elsevier B.V.)

Mucoadhesive molecules such as chitosan, can allow targeting of a particular tissue to prolong residence time and subsequently improve bioavailability. The purpose of this study was to investigate chitosan-tripolyphosphate (CS:TPP) nanoparticles and to evaluate the interaction between nanoparticles of different CS:TPP ratios with mucin using viscosity, particle size analysis and ζ-potential. For all CS:TPP ratios examined, a minimum value of viscosity was reached for a 3:1 CS:TPP ratio, however chitosan nanoparticles at this ratio were not stable (<+30 mV), whereas a CS:TPP ratio of 4:1 displayed the strongest interaction. This suggests a minimum CS:TPP ratio of 4:1 is required to produce stable nanoparticles able to form strong interactions, which is consistent with a greater mucin binding efficiencies at CS:TPP ratios of 4:1 and higher, which were quantified using a colorimetric assay. Further analysis of similar systems could lead potentially to tuneable chitosan nanoparticles for specific applications., (Copyright © 2018 Elsevier B.V. All rights reserved.)

In the present study due to the distinctive mechanochemical/biological characteristics of natural biomembranes, we state the preparation, characterization and cytocompatibility of modified eggshell membrane (ESM) by citric acid (CA) for biomedical and pharmaceutical applications. FTIR spectroscopy and CHNS analysis demonstrated the successful reaction of ESM with CA. Also, successful modification of the ESM was observed by the change in thermogravimetric analysis. SEM micrographs of neat ESM and ESM-CA gave further insight into membranes morphology and revealed that aligned oriented fibrous frameworks were prepared using thermo-chemical process. The ESM-CA displayed dense and orderly shapes with tailorable architectures to mimic the intended tissue. Moreover, mechanical analyzes for ESM-CA indicated anisotropic mechanical properties and proved that the ESM-CA could induce enhanced mucoadhesion, because of the existence of an enormous amounts of functional groups. It was found that by modification of ESM the swelling behavior was significantly changed. Indomethacin release from the ESM-CA showed enhanced pH sensitivity. The modified membranes have clearly presented adequate mucoadhesion, pH sensitivity and cell viability which can be tailored for potential use in controlled lipophilic drug delivery systems and tissue engineering., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

A large number of drugs are administered on different mucosal surfaces. However, due to the poor mucoadhesion of the current formulations, their bioavailability is often very low. The development of efficient mucoadhesive drug delivery systems is thus crucial for improving the performance of these drugs. The mucoadhesive properties of gold nanoparticles were investigated. First, two types of gold nanoparticles were synthesized: AuNP1 and AuNP2. AuNP1 only contain internal thiol groups on their metallic core, and AuNP2 contain both internal and peripheral thiol groups. Different protocols based on an adapted quantitative colorimetric method, UV-visible and fluorescence spectroscopies were then developed to gather information on their mucoadhesive properties. Moreover, a global correction factor for the inner filter effect in spectrofluorimetry was proposed, and the data obtained were compared to those commonly used in the literature. Mucins deeply interact with AuNP1, perturbing their core, whereas they remain at the periphery of AuNP2. The quantitative method suggests that a larger number of mucins interact with AuNP2. The establishment of this protocol could be applied to assess the mucoadhesive properties of other stable molecules. This mucoadhesive property of gold nanoparticles could be combined with their drug delivery ability in order to improve the medication administered on mucosa.

Recently, chitosan-based nanoparticles with mucoadhesive properties emerged as a strategy for mucosal drug release. This study aimed to characterize the interaction of mucoadhesive system chitosancoated PLGA nanoparticles (NPMA) with fish external mucus. NP suspensions with fluorescent probe were prepared and characterized by size, polydispersity, zeta potential and pH measures. In post-exposure fish were observed an increase in fluorescence imaging over time and it was significantly influenced by NPMA concentration. We also observed the main predominance the fluorescence in the spleen, followed by liver, gill and other tissues. The use of mucoadhesive nanocarriers becomes an alternative for administration of drugs and immunomodulators in immersion systems since the nanosystem can adhere to the mucosal surface of the fish with little residual effect in the water., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Chitosan-alginate microspheres (MS) were developed for cefixime vaginal administration, to overcome problems associated with its oral administration. The effect of increasing drug-loading amount, by keeping the chitosan-alginate content constant, was investigated. Mucoadhesion studies indicated that all formulations assured in situ permanence longer than 2 h. Entrapment efficiency increased with drug loading concentration in the starting solution, reaching a plateau at 30 mg/mL indicative of the achievement of an optimal drug-to-polymer ratio. MS swelling properties increased with the entrapped drug amount, and, interestingly, water-uptake reached its maximum value at the same drug loading concentration of 30 mg/mL. The relationship found between MS water-uptake and drug release rate confirmed MS prepared with 30 mg/mL cefixime as the best formulation. Microbiological studies showed a relation between cefixime release rate from MS and Escherichia coli viability reduction, definitely indicating the selected MS formulation as the best for an effective local treatment of urogenital infections., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

trans-Aconitic acid (TAA) is the main constituent of the leaves from the medicinal plant Echinodorus grandiflorus, used to treat different inflammatory diseases. TAA induces a potent but short-lasting biological response, credited to its high polarity and unfavorable pharmacokinetics. Here we developed, characterized and evaluated the anti-inflammatory activity of mucoadhesive microspheres loaded with TAA. Seven batches of mucoadhesive microspheres were prepared by the emulsification/solvent evaporation method, employing different proportions of TAA and Carbopol 934 or/and hydroxypropylmethylcellulose. All batches were characterized for their particle medium size, polydispersity index and entrapment percentage. The batch coded F3c showed highest entrapment percentage and was characterized by infrared spectroscopy (ATR-FTIR), scanning electron microscopy (SEM), differential scanning calorimetry (DSC), thermogravimetric analyses (TGA) and zeta potential. The anti-inflammatory activity of F3c was assessed in a model of acute arthritis induced by injection of LPS in the knee joint of Swiss mice. The granulometric analyses indicated heterogeneous size distribution for F3c. SEM characterization indicated microspheres with slightly irregular shape and rough surface. Results from ATR-FTIR and thermal analyses (DSC and TGA) pointed out absence of incompatibility between the components of the formulation; thermal events related to the constituents were isolated and randomly located, suggesting amorphous distribution of TAA in the formulation matrix. The zeta potential of the formulations varied from -30 to -34 mV, which may contribute to good stability. When given orally to mice, F3c induced a prolonged anti-inflammatory response by reducing total cell count and neutrophilic accumulation in the joint cavity even when given 48 and 36 h before the stimulus, respectively, in comparison to free TAA (up to 24 and 6 h, respectively). Therefore, the encapsulation of TAA in mucoadhesive microspheres provided its sustained release, indicating that this drug delivery system is a potential agent to treat inflammatory diseases by regulating cell influx., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Cervical gastric-type adenocarcinomas are aggressive non-human papillomavirus-related carcinomas with a propensity for extracervical spread, including unusual sites such as the omentum, peritoneum, and ovary. We report 7 cases of cervical gastric-type adenocarcinoma with fallopian tube involvement predominantly in the form of mucosal colonization without underlying invasion. As far as we are aware, this has not been previously described and this report adds to the literature regarding metastatic neoplasms, which may exhibit tubal mucosal involvement and mimic an in situ lesion at this site. In all cases, there was associated ovarian involvement and in 6 of 7 cases, there was endometrial colonization. We speculate that the fallopian tube (and ovarian) involvement is secondary to transuterine spread. Given the occasional occurrence of multifocal gastric-type glandular lesions (benign or malignant) involving different sites in the female genital tract, we discuss the distinction between synchronous independent and metastatic lesions.