Effects of Polymannuronic Acid on the Intestinal Microbiota in Mice after Long-Term Intragastric Administration.

Polymannuronic acid (PM) is an alginate oligosaccharide derived from brown algae with a characterized structure and excellent biological activities. Herein, mice were given different doses of PM through 30-day-long-term intragastric administration, and the contents of the jejunum, ileum, and colon were analyzed by 16S rRNA gene sequencing technology for microbial diversity, and relevant experiments were verified according to the analysis results so as to comprehensively evaluate the effects of PM on the intestinal flora. The PM (400 mg/kg and 100 mg/kg) could regulate the microflora balance at the phylum level and increase the microflora richness in the jejunum, ileum, and colon of the mice. The PM could induce more strains that are negatively correlated with Escherichia, thereby reducing the relative abundance of Escherichia. Analysis of bacterial function showed that high and low doses of PM could promote lipid metabolism in the bacterial communities. Moreover, the PM could reduce serum total cholesterol and cholesterol ester levels in a concentration-dependent manner. High-dose PM could lead to colonic intestinal inflammation by increasing the relative abundance of multiple bacterial groups in the jejunum, ileum, and colon. Moreover, high-dose PM could increase lipopolysaccharide-binding protein and interleukin-1ß levels. Therefore, the dose of PM plays an important role in its efficacy, and its biological activity is dosedifferent.

In situ formation of alginic acid-gold nanohybrids for application in cancer photothermal therapy.

Gold-based nanoparticles present excellent optical properties that propelled their widespread application in biomedicine, from bioimaging to photothermal applications. Nevertheless, commonly employed manufacturing methods for gold-based nanoparticles require long periods and laborious protocols that reduce cost-effectiveness and scalability. Herein, a novel methodology was used for producing gold-alginic acid nanohybrids (Au-Alg-NH) with photothermal capabilities. This was accomplished by promoting the in situ reduction and nucleation of gold ions throughout a matrix of alginic acid by using ascorbic acid. The results obtained reveal that the Au-Alg-NHs present a uniform size distribution and a spike-like shape. Moreover, the nanomaterials were capable to mediate a temperature increase of ≈11°C in response to the irradiation with a near-infrared region (NIR) laser (808 nm, 1.7 W cm-2 ). The in vitro assays showed that Au-Alg-NHs were able to perform a NIR light-triggered ablation of cancer cells (MCF-7), being observed a reduction in the cell viability to ≈27%. Therefore, the results demonstrate that this novel methodology holds the potential for producing Au-Alg-NH with photothermal capacity and higher translatability to the clinical practice, namely for cancer therapy.

Insight on updates in polysaccharides for ocular drug delivery.

Ocular drug delivery is a significantly challenging task due to the presence of various anatomical and physiological barriers in the eye. Naturally available polysaccharides, when used as drug vehicles provide increased retention time, bioavailability, and penetration due to their unique mucoadhesive and charge-possessing nature. This review discusses the polysaccharide-based drug delivery system for the eye. Polysaccharides like alginic acid, cellulose derivatives, chitosan, pectin, xanthan gum, gellan gum, and hyaluronic acid are reviewed in this report. Additionally, emphasis is given to some of the recently investigated polymers such as sugarcane bagasse cellulose, a polysaccharide extracted from the seeds of Manilkara zapota, and Tremella fuciformis polysaccharide as drug vehicles for effective ocular drug delivery. This review also provides insight on clinical status and FDA-approved polysaccharides for ophthalmic delivery of therapeutics.

Immunomulation effect of alginic acid and chitooligosaccharides in silver carp (Hypophthalmichthys molitrix).

Individual and combined efficacy of chitooligosaccharides (COS) and alginic acid (AA) at 1 g, 2 g, and 3 g per kg diet was assessed on growth and disease resistance in silver carp (Hypophthalmichthys molitrix) against Edwardsiella ictaluri. Growth parameters including specific growth rate (SGR), weight gain (WG), and feed conversion rate (FCR) were significant in fish fed 2 g and 3 g kg-1 of COS or AA, and fish fed combined COS + AA at 1, 2 and 3 kg-1 diet. In all groups, the survival rate (SR) was recorded 100%, except in group fed 2 g kg-1 AA diet. All the hematological and biochemical profiles significantly increased in groups fed 2 g and 3 g kg-1 of COS, AA, and COS + AA diets. Lipase and amylase enzyme activities and superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GPx) antioxidant enzyme activities were significantly increased in fish fed 2 g and 3 g kg-1 of COS, AA, and COS + AA diet. Respiratory burst (RB), lysozyme (Lyz), reactive oxygen species (ROS) activities, and immunoglobuline (Ig) level were enhanced significantly in fish fed 2 g kg-1 of COS or COS + AA and all 3 g kg-1 diets, whereas nitric acid (NO) production and serum AP activity were improved in 2 g kg-1 COS + AA and 3 g kg-1 COS or COS + AA diets. Pro-inflammatory cytokine such as IL-8 mRNA transcriptions was significant in 2 g kg-1 COS + AA diet and all 3 g kg-1 diet. The IL-10 anti-inflammatory cytokine mRNA transcriptions were significant in 3 g kg-1 COS or COS + AA diets. This study was confirmed that H. molitrix fed with 3 g kg-1 COS or COS + AA diets were better activity when compared to other diet.

Alginic acid inhibits non-small cell lung cancer-induced angiogenesis via activating miR-506 expression.

Angiogenesis is a key event in non-small cell lung cancer progression. Alginic acid (AA), a kind of naturally occurring polyuronic acid, is generally enriched in edible brown algae. Recent studies have uncovered its anti-anaphylactic and anti-inflammatory properties. However, the effects of AA on human malignancies remain unknown. Herein, efficient inhibition of AA on NSCLC-induced angiogenesis was observed with tube formation and xenograft models. Subsequent results indicated that AA downregulated the expression of VEGF-A, a key angiogenesis-inducing cytokine. In addition, AA downregulated STAT3, a transcriptional inducer of VEGF-A and increased non-coding RNA miR-506 expression, respectively. Furthermore, miR-506 directly modulated STAT3 relying on base pairing the 3'-UTR in STAT3 mRNA. We also found that abrogation of miR-506 abolished the inhibitory effect of AA on VEGF-A expression and NSCLC-induced angiogenesis. Finally, xenografts experiments also showed that oral administration of AA could significantly attenuate NSCLC angiogenesis, indicated by decreased micro-vessel density (MVD) and the MVD marker CD31 expression in xenografts tissues. Correspondingly, AA treatment also downregulated VEGF-A, STAT3 and increased miR-506 expression in xenografts samples, respectively. Taken together, these results suggested that AA could suppress NSCLC-induced angiogenesis via miR-506/STAT3/VEGF-A axis. .

Preparation and evaluation of conjugate nanogels of glycyl-prednisolone with natural anionic polysaccharides as anti-arthritic delivery systems.

Although prednisolone (PD) is used as an anti-arthritis drug due to its rapid and strong anti-inflammatory potential, its frequent and large dosing often brings about adverse effects. Therefore, targeting therapy has attracted increasing attention to overcome such adverse effects. In the present study, nanogels (NGs) composed of macromolecule-PD conjugates were developed as a novel targeting delivery system, and their anti-inflammatory potential was examined. Conjugates were prepared by carbodiimide coupling between glycyl-prednisolone (GP) and the natural anionic polysaccharides, alginic acid (AL) and hyaluronic acid (HA). NGs were produced by the evaporation of organic solvent from the conjugate solution. The obtained NGs, named AL-GP-NG and HA-GP-NG, respectively, were examined for particle characteristics, in vitro release, pharmacokinetics, and in vivo efficacy. Both NGs were several hundred nanometers in size, had negative zeta potentials, and several % (w/w) drug contents. They released PD gradually at pH 7.4 and 6. They exhibited fairly good retention in the systemic circulation. In the efficacy examination using rats with adjuvant-induced arthritis, both NGs showed the stronger and more prolonged suppression of paw inflammation than PD alone. These suggested that the present NGs should be possibly useful as anti-arthritis targeting therapeutic systems.

Bioactivity of alginetin, a caramelization product of pectin: Cytometric analysis of rat thymic lymphocytes using fluorescent probes.

Alginetin is the major product formed from pentoses and hexurionic acids. Alginetin is producted by cooking process of food including pection, a naturally-occurring polysacharride found in many plants. However, the biological interaction and toxicity of alginetin are not known at all. The aim of the present study was to investigate the cellular actions of alginetin on rat thymic lymphocytes. The effects of alginetin on the cell were examined using flow cytometry with fluorescent probes. Alginetin increased cellular content of non-protein thiols ([NPT]i) and elevated intracellular Zn2+ levels ([Zn2+]i). Chelation of intracellular Zn2+ reduced the effect of alginetin on [NPT]i, and chelation of external Zn2+ almost completely diminished alginetin-induced elevation of [Zn2+]i, indicating that alginetin treatment increased Zn2+ influx. Increased [NPT]i and [Zn2+]i levels in response to alginetin were positively correlated. Alginetin protected cells against oxidative stress induced by hydrogen peroxide and Ca2+ overload by calcium ionophore. It is considered that the increases in [NPT]i and [Zn2+]i are responsible for the cytoprotective activity of alginetin because NPT attenuates oxidative stress and Zn2+ competes with Ca2+. Alginetin may be produced during manufacturing of jam, which may provide additional health benefits of jam.

Structure-Properties Relationship in the Evaluation of Alginic Acid Functionality for Tableting.

The aim of this study is to investigate the relationship between the structural, molecular, and particulate properties of alginic acid and its functional characteristics in direct compression (tabletability, compressibility, elasticity, deformation mechanism, and disintegration ability). Therefore, accurate characterization of two different batches of alginic acid was executed (X-ray powder diffraction, Fourier-transform infrared spectroscopy, thermogravimetric analysis, scanning electronic microscopy, 1H nuclear magnetic resonance, size exclusion chromatography - multi angle light scattering, viscosimetry, carboxylic acid titration, powder flowability, true density, laser granulometry). Results showed that molecular weight seems to affect tablet properties and that the alginic acid with the lowest molecular weight provides the hardest tablets with the lowest elastic recovery. Furthermore, these results show the potential interest of exploiting alginic acid as filler excipient in tablet formulation. Finally, disintegration properties of tested materials were found to be close to that of commercial superdisintegrants (Glycolys® and Kollidon Cl®) but not correlated to their swelling force. It can be concluded, for the first time, that the determination of alginic acid molecular weight seems key for applications in direct compression and in particular for obtaining tablets with reproducible strength.

Hydrogels as a water bolus during hyperthermia treatment.

The feasibility of using hydrogels as a water bolus during hyperthermia treatment was assessed. Three types of gels, high methoxyl (HM) pectin/alginate, xanthan/locust bean gum (LBG) and xanthan/LBG/agarose were evaluated based on their dielectric, rheological and mechanical properties. The most suitable, xanthan/LBG/agarose gel was further used as a water bolus in a hyperthermia array applicator. The gels composed of polysaccharides carrying low charge displayed dielectric properties close to those of water, while the dielectric properties of HM pectin/alginate gel was deemed unsuitable for the current application. The mechanical examination shows that the xanthan/LBG gel has a non-brittle behaviour at room temperature, in contrast to the agarose gel. The moduli of the xanthan/LBG gel weaken however considerably between the temperature range of 40 °C and 50 °C, reducing its potential to be used as water bolus. The ternary system of xanthan/LBG/agarose had advantageous behaviour as it was dominated by the thermal hysteresis typical of agarose upon temperature increase, but governed by the typical non-brittle behaviour of the xanthan/LBG at low temperatures. The final evaluation within the hyperthermia applicator showed excellent signal transmission from the antennas. The agarose/xanthan/LBG gel reduced the scattering of electromagnetic waves, enabled a tight closure between the body and the antennas, and offered a less bulky solution than the currently used water-filled plastic bags. The results presented here open up a new application area for hydrogels in improving heat delivery during hyperthermia treatment and other near-field microwave applications.

Multi-Drug Resistant Clinical Pseudomonas aeruginosas Inhibited by Ferula gummosa Boiss.

BACKGROUND: Multi-drug resistance among Pseudomonas aeruginosa (P. aeruginosa) clinical isolates is increasing and becoming a serious problem for public health authorities worldwide. OBJECTIVE: The aim of the current study is to introduce a potent antibacterial compound against the resistant P. aeruginosa. METHODS: In this study, we evaluated the antibacterial effects of extracts and essential oils of Ferula gummosa Boiss (F. gummosa) on 33 P. aeruginosa clinical isolates by microdilution method and assessed the association of antimicrobial activity with the extended spectrum ß-lactamase (ESBL) producing, biofilm forming and aliginate production of the strains. In addition, the presence of some genes involved in these properties, including blaGES- 1, blaRER-1, blaCTX-M, blaVEB-1, blaOXA-1, blaOXA-4, blaOXA-10, ppyR, pslA, pelA, algU, algL, algD, fliC and oxaA was determined using PCR. RESULTS: We revealed that all of our extracts and essential oils had significant antibacterial effects (p<0.001), but the aqueous extracts showed a relatively lower antibacterial activity compared with the methanolic ones. Furthermore, the minimum inhibitory concentration required for the ESBL producing strains was significantly higher than the non-ESBL producing ones (p<0.001). Loss of some genes such as blaPER-1, blaGES-1, blaOXA-1 and blaOXA-4 caused sensitivity to F. gummosa derivatives (p<0.05). CONCLUSION: The findings of this study indicate that the antibacterial effects of the extract and essential oils of F. gummosa may be a potential novel treatment against drug-resistant P. aeruginosa clinical isolates.

Design of Phase-Changeable and Injectable Alginate Hydrogel for Imaging-Guided Tumor Hyperthermia and Chemotherapy.

The objective of the present study was to construct an alginate (AG)-based phase-changeable and injectable hydrogel for imaging-guided tumor hyperthermia and chemotherapy. Based on the binding between the α-l-guluronic blocks of AG and calcium ions, the AG/MoS2/Bi2S3-poly(ethylene glycol) (MBP)/doxorubicin (DOX) solution formed a cross-linked hydrogel to simultaneously encapsulate MBP nanosheets and DOX within the hydrogel matrix. The in situ formed hydrogel can act as a reservoir to control the release of entrapped drug molecules, and the doped MBP nanosheets and DOX can realize computed tomography/photoacoustic dual-modal imaging-guided in vivo tumor photothermal therapy and chemotherapy, respectively. The AG/MBP/DOX hydrogel exhibited excellent photothermal conversion properties with mass extinction coefficient of 45.1 L/g/cm and photothermal conversion efficiency of 42.7%. Besides, the heat from the photothermal transformation of MBP can promote drug diffusion from the hydrogel to realize on-demand drug release. Additionally, the hydrogel system can restrain MBP and DOX from entering into the blood stream during therapy, and therefore substantially decrease their side effects on normal organs. More importantly, the drug loading of the AG hydrogel was general and can be extended to the encapsulation of antibiotics, such as amoxicillin, for the prevention of postoperative infections.