Water-soluble Chitosan Oligosaccharide Research Articles

Evaluation of corrosion inhibition efficiency of chitosan oligosaccharide-derived quaternary ammonium vanillyl aldehyde oligosaccharide derivative for CO2 corrosion control

This study presents the synthesis of a non-toxic, water-soluble chitosan oligosaccharide derivative, quaternary ammonium vanillyl aldehyde oligosaccharide (GCOS), using chitosan oligosaccharide, vanillin, and 2,3-epoxypropyltrimethylammonium chloride as precursors, aimed at serving as a novel eco-friendly corrosion inhibitor. The successful synthesis of the derivative was confirmed through Fourier Transform Infrared Spectroscopy (FTIR) and Proton Nuclear Magnetic Resonance (1H NMR) analysis. The corrosion inhibition properties of GCOS on 20# carbon steel were investigated in a 60 °C CO2-saturated 3.0 wt% NaCl solution employing an array of methods including weight loss measurements, Scanning Electron Microscopy (SEM), Atomic Force Microscopy (AFM), electrochemical characterization, and molecular dynamics simulation. Additionally, the synergistic effect of protonated GCOS with halide ion Cl- on corrosion inhibition was analyzed at the molecular level. The results indicated an enhancement in inhibition efficiency with increasing concentrations of the inhibitor. Weight loss measurements showed a maximum inhibition efficiency of 90.9% at 200 ppm of GCOS after 3 days. The adsorption of GCOS on the carbon steel surface was found to follow the Langmuir adsorption isotherm, predominantly through chemisorption. Potentiodynamic polarization measurements classified GCOS as a mixed-type inhibitor, affecting both anodic and cathodic reactions by blocking the active corrosion sites. SEM and AFM analyses confirmed the formation of a protective inhibitor film on the metal surface. Furthermore, molecular dynamics simulations elucidated the synergistic corrosion inhibition effect between the protonated GCOS molecules and Cl- ions in the acidic solution.

Inhibition of carbon steel corrosion in CO2-saturated 3.5 wt.% NaCl solution by vanillin chitosan oligosaccharide and synergistic effect of KI additive

The chitosan oligosaccharide and vanillin are used as raw materials to synthesize non-toxic and water-soluble chitosan oligosaccharide derivative called vanillin chitosan oligosaccharide as a green corrosion inhibitor. The corrosion inhibition properties of 20# steel in CO2-saturated solution system at 25°C and 3.5 wt% NaCl were studied. The synergistic effect of potassium iodide (KI) and VCOS on corrosion inhibition was also studied. Various techniques such as weight loss (WL), electrochemical analysis, atomic force microscopy (AFM), scanning electron microscopy (SEM), quantum chemical calculations, and molecular dynamics simulations were used to understand the inhibition properties. The inhibition efficiency of VCOS enhanced remarkably after the addition of KI, reaching an optimum value of 93.1%. EIS results showed that the inhibition of VCOS + KI on metal surface increased with time. Polarization measurements showed that VCOS and KI acted as mixed inhibitors by demonstrating anode dominance. SEM and AFM were used to study the formation of inhibition film on metal surface after 3 days immersion. We concluded that the mixed inhibitor followed Langmuir adsorption isotherm. In addition, quantum chemistry and molecular dynamics simulations were used to verify the relationship between corrosion inhibition efficiency and molecular structure.

Preparation of water-soluble chitosan oligosaccharides by oxidative hydrolysis of chitosan powder with hydrogen peroxide

Chitosan (CS) is only soluble in weak acid medium, thereby limiting its wide utilisation in the field of biomedicine, food, and agriculture. In this report, we present a method for preparing water-soluble CS oligosaccharides (COSs) at high concentration (∼10%, w/v) via the oxidative hydrolysis of CS powder with molecular weight (Mw) ∼90,000 g/mol) in 2% H2O2 solution at ambient temperature by a two-step process, namely, the heterogeneous hydrolysis step and homogeneous hydrolysis step. The resultant COSs were characterised by gel permeation chromatography (GPC), fourier transforms infrared spectroscopy (FT-IR), ultraviolet–visible spectroscopy (UV–Vis), proton nuclear magnetic resonance spectroscopy (1H NMR) and X-ray diffraction (XRD) spectroscopy. The resulting products were composed of COSs (Mw of 2000−6600 g/mol) that were completely soluble in water. The results also indicated that the structure of COSs was almost unchanged compared with the original CS unless Mw was low. Accordingly, COSs with low Mw (∼2000 g/mol) and high concentration (10%, w/v) could be effectively prepared by the oxidative hydrolysis of CS powder using hydrogen peroxide under ambient conditions.

Biological elicitors to enhance wound healing responses in cut potato tubers

Wounding-induced postharvest losses of potato tubers is a serious economic problem in the United States (≥$320 million year−1) and globally. Developing safe and effective postharvest treatment strategy to enhance wound-healing (WH) responses is extremely important to mitigate wound-induced potato tuber losses. Formation of protective suberin layer in the wound surface is the primary WH response of potato tubers. In this study, biological elicitor based postharvest treatment strategy using water-soluble chitosan oligosaccharide (COS 0.125 g L−1), and phenolics-rich cranberry pomace (Nutricran 0.125 g L−1) was employed to accelerate formation of suberin layer in wounded potato tubers. A standardized disk model system was used to study WH responses in certified mini tubers of cv. Russet Burbank and cv. Russet Norkotah, 4 days after wounding. The effects of these elicitor treatments on the regulation of pentose phosphate pathway (PPP) and associated antioxidant enzyme responses were investigated as key control points for improving suberization and related WH processes in wounded potato tubers. Postharvest treatments of COS and Nutricran resulted in improved accumulation of suberin polyphenolics (SPP) in wounded tissues of both potato cultivars after 4 days of WH when compared to control (buffer treatment). Additionally, higher soluble phenolic content, enhanced activity of glucose-6-phosphate dehydrogenase (G6PDH), guaiacol peroxidase (GPX), and catalase (CAT) were observed in COS-treated tissues of cv. Russet Burbank. Therefore, COS postharvest treatment can be integrated and optimized in further investigations to potentially improve suberization and WH processes in wounded potato tubers.

Photosensitive pro-drug nanoassemblies harboring a chemotherapeutic dormancy function potentiates cancer immunotherapy.

Immunotherapy combined with effective therapeutics such as chemotherapy and photodynamic therapy have been shown to be a successful strategy to activate anti-tumor immune responses for improved anticancer treatment. However, developing multifunctional biodegradable, biocompatible, low-toxic but highly efficient, and clinically available transformed nano-immunostimulants remains a challenge and is in great demand. Herein, we report and design of a novel carrier-free photo-chemotherapeutic nano-prodrug COS-BA/Ce6 NPs by combining three multifunctional components-a self-assembled natural small molecule betulinic acid (BA), a water-soluble chitosan oligosaccharide (COS), and a low toxic photosensitizer chlorin e6 (Ce6)-to augment the antitumor efficacy of the immune adjuvant anti-PD-L1-mediated cancer immunotherapy. We show that the designed nanodrugs harbored a smart and distinctive "dormancy" characteristic in chemotherapeutic effect with desired lower cytotoxicity, and multiple favorable therapeutic features including improved 1O2 generation induced by the reduced energy gap of Ce6, pH-responsiveness, good biodegradability, and biocompatibility, ensuring a highly efficient, synergistic photochemotherapy. Moreover, when combined with anti-PD-L1 therapy, both nano-coassembly based chemotherapy and chemotherapy/photodynamic therapy (PDT) could effectively activate antitumor immunity when treating primary or distant tumors, opening up potentially attractive possibilities for clinical immunotherapy.

Chitosan Oligosaccharide Lactate Increases Productivity and Quality of Baby Leaf Red Perilla

Perilla (Perilla frutescens) belongs to the Lamiaceae family, is used as a spicy culinary herb leafy vegetable as well as medicinal and ornamental plant. However, little is known about protocols for baby leaf perilla production. Native chitosan is a well-known biostimulant used in crop plant production. Nevertheless, the influence of water-soluble chitosan oligosaccharide lactate (ChOL) on plant growth and bioactive compounds content remains unknown. The present pot experiment determines the effects of ChOL (0, 50 and 100 mg/L) on growth and selected biochemical characteristics of baby leaf red perilla. Compared to the untreated plants, ChOL application at 50 and 100 mg/L increased plant height (by 14.6% and 13.2%), the fresh weight of the above-ground part of plants (by 17.1% and 26.7%), leaves (by 21.8% and 35.5%) and roots (by 52.2%). The levels of total reducing sugars, polyphenolics, flavonoids and anthocyanins in perilla leaves were significantly higher in all plants treated with ChOL at all tested concentrations. This was confirmed by macromolecules (FT-IR) studies showing higher band intensity for key functional groups in leaf samples. The application of ChOL also enhanced the antioxidant activity by using DPPH, ABTS and O2− radical scavenging activity assays. Based on the research, results suggested that ChOL may be used an effective plant biostimulant for high quality production of baby leaf red perilla.

Using Biological Elicitation to Improve Type 2 Diabetes Targeted Food Quality of Stored Apple

Food quality improvements of fresh fruits targeting both food preservation and human health is essential to advance healthy dietary options and to mitigate imbalanced nutrition-linked non-communicable chronic disease (NCDs) challenges globally. Specifically, protective phenolic bioactives of fruits with dual functional benefits can be harnessed to advance innovations for improving nutritional quality and post-harvest shelf-life of perishable fruits. Based on this rationale the dual functional benefits of plant phenolics were harnessed using novel biological elicitation strategies to modulate phenolic bioactive-linked protective responses in apple during storage in two interrelated studies. Bioprocessed food-grade elicitors [water soluble chitosan oligosaccharide -(COS) and phenolic enriched oregano extracts-(OX)] were targeted as post-harvest dipping treatments (2 & 4 g/ L) and compared with diphenylamine (DPA) (1 & 2 g/L) to enhance phenolic-linked antioxidant and anti-diabetic (type 2 diabetes) relevant properties of Cortland apple during 3 months of storage (4°C). The selection of bio-elicitors and respective doses were based on the foundations of the previous related study, which resulted in reduction of superficial scald of Cortland apple during storage. Apples sampled over 3 months as aqueous and ethanol (12%) extracts of peel and pulp were analyzed separately for total soluble phenolic content, phenolic profile, antioxidant activity, and glucose metabolism relevant α-amylase and α-glucosidase enzyme inhibitory activities using in vitro assay models. Enhanced soluble phenolic content and associated antioxidant activity were observed in ethanol (12%) extracts of apple peel with 4 g/L COS elicitor treatments after 2 and 3 months of storage. High chlorogenic acid and quercetin derivatives were found in peel extracts of Cortland apple, while pulp extracts had high chlorogenic and gallic acids. Additionally, high α-glucosidase enzyme inhibitory activity, which is relevant for managing post-prandial hyperglycemia of type 2 diabetes was also observed in bio-elicited apple peel and pulp extracts. Therefore, results of these two interrelated studies indicate that bioprocessed food grade elicitor such as OX and COS can be recruited as a novel tool to enhance protective phenolic responses for improving type 2 diabetes targeted food quality and post-harvest storage quality of apple.

Preparation of Polyurea Microcapsules by Interfacial Polymerization of Isocyanate and Chitosan Oligosaccharide.

(2-((1-(4-chlorophenyl)-1H-pyrazol-3-yl)oxy)-N-(3,4-dichlorophenyl)-propanamide) is a new oil-soluble compound with good fungicidal activity against Rhizoctonia solani. Chitosan oligosaccharide (COS) is the depolymerization product of chitosan and can be developed into biological pesticides, growth regulators, and fertilizers due to its various bioactivities. COS is an oligomer of β- (1 → 4)-linked d –glucosamine and can be taken as a polyamine. In this study, microcapsules were prepared by interfacial polymerization of oil-soluble methylene diphenyl diisocyanate and water-soluble COS. The effects of several key preparation parameters, e.g., emulsifier dosage, agitation rate during emulsification, and core/shell ratio, on properties of the microcapsules such as the encapsulation efficiency, particle size, and size distribution were investigated. The microcapsules were characterized by infrared spectroscopy, thermogravimetric analysis, and scanning electron microscopy, etc., and the encapsulation efficiency and release behaviors were investigated. The results show that the microcapsules have a smooth surface and 93.3% of encapsulation efficiency. The microcapsules showed slow-release behavior following a first-order kinetic equation, and the accumulative release rates of the microcapsules with core/shell mass ratios of 8.0/4.0, 8.0/5.0, and 8.0/6.0, were 95.5%, 91.4%, and 90.1%, respectively, on day 30. Due to many high biological activities, biodegradability, and the pure nature of COS, microcapsules formed from COS are promising for applications in controlled release of pesticides, growth regulators, and fertilizer.

Anti-inflammatory Effect of Water-soluble Chitosan Oligosaccharideson Human Monocyte THP-1 Cells

The various functional properties of chitosan have been investigated for use in biomedical applications. Indeed, chitosan or its derivatives have shown anti-inflammatory effect by regulating a range of cytokines, chemokines or growth factors. In the present study, we prepared water-soluble chitosan oligosaccharide (AS-WSC) by the hydrolysis of high molecular weight water-soluble chitosan (HMW-WSC) and examined its anti-inflammatory effect on LPS-stimulated human monocytic THP-1 cells. Our results revealed that LPS-induced NF-κB activity of THP-1 cells was significantly suppressed by treatment with 0.02% AS-WSC. In addition, 0.02% AS-WSC treatment down-regulated the expression of Toll-like receptor 4 and inflammatory cytokines, such as IL-1β and TNF-α, but had no effect on IL-10 and IL-4 expression in LPS-stimulated THP-1 cells. Our results suggest that 0.02% AS-WSC can be considered as a promising anti-inflammatory agent.

Synthesis and Evaluation of a Chitosan Oligosaccharide-Streptomycin Conjugate against Pseudomonas aeruginosa Biofilms.

Microbial biofilms are considerably more resistant to antibiotics than planktonic cells. It has been reported that chitosan coupling with the aminoglycoside antibiotic streptomycin dramatically disrupted biofilms of several Gram-positive bacteria. This finding suggested the application of the covalent conjugate of antimicrobial natural polysaccharides and antibiotics on anti-infection therapy. However, the underlying molecular mechanism of the chitosan-streptomycin conjugate (CS-Strep) remains unclear and the poor water-solubility of the conjugate might restrict its applications for anti-infection therapy. In this study, we conjugated streptomycin with water-soluble chitosan oligosaccharides (COS). Unlike CS-Strep, the COS-streptomycin conjugate (COS-Strep) barely affected biofilms of tested Gram-positive bacteria. However, COS-Strep efficiently eradicated established biofilms of the Gram-negative pathogen Pseudomonas aeruginosa. This activity of COS-Strep was influenced by the degree of polymerization of chitosan oligosaccharide. The increased susceptibility of P. aeruginosa biofilms to antibiotics after conjugating might be related to the following: Suppression of the activation of MexX-MexY drug efflux pump system induced by streptomycin treatment; and down-regulation of the biosynthesis of biofilm exopolysaccharides. Thus, this work indicated that covalently linking antibiotics to chitosan oligosaccharides was a possible approach for the development of antimicrobial drugs against biofilm-related infections.

Preparation, physicochemical properties and biocompatibility of biodegradable poly(ether-ester-urethane) and chitosan oligosaccharide composites

In the paper, novel composites of biodegradable poly(ether-ester-urethane) (PEEU) and water-soluble chitosan oligosaccharide (CHO) were prepared using a simple physical mixing method and their potential application as biomaterials was assessed. The PEEU and CHO were dissolved in N,N-dimethylformamide to get a homogenous solution, then the composite films were obtained by the solvent evaporation method. The composites were characterized by FT-IR, and the influence of CHO content on the physicochemical properties of the composite films, including thermal properties, surface morphologies, mechanical properties, surface and bulk hydrophilicity, and in vitro biodegradability, were researched. The thermal stability studies indicated that the composite films had lower initial decomposition temperature and higher maximum decomposition temperature than PEEU film. Only one broad endothermic peak found in DSC curves demonstrated the high compatibility of CHO with PEEU. The ultimate stress and elongation at break of composite films decreased with the increment of CHO content, and the CHO content in the composites should be controlled no more than 25 wt% in order to maintain the mechanical properties (ultimate stress: 18.5 MPa; elongation at break: 890%) to meet the requirement of implant materials. The surface morphologies of composite films were observed by cold field emission scanning electron microscope (FE-SEM), and the results indicated that the homogeneous-dispersed composites could be obtained with CHO content being less than 20 wt%. The results of water contact angle and water absorption showed that the surface and bulk hydrophilicity were closely related with the water-solubility of CHO component. In vitro degradation studies showed that the degradation rate increased with the increasing content of CHO in composites, indicating that the degradation rate of composite films could be controlled by adjusting CHO content. The surface blood compatibility of the composite films was examined by bovine serum albumin adsorption and platelet adhesion tests. It was found that composite films had improved resistance to protein adsorption and possessed excellent resistance to platelet adhesion.

Chitosan oligosaccharides affect xanthone and VOC biosynthesis in Hypericum perforatum root cultures and enhance the antifungal activity of root extracts

Water-soluble chitosan oligosaccharides (COS) affect xanthone and volatile organic compound content, as well as antifungal activity against human pathogenic fungi of extracts obtained from Hypericum perforatum root cultures. Several studies have demonstrated the elicitor power of chitosan on xanthone biosynthesis in root cultures of H. perforatum. One of the major limitations to the use of chitosan, both for basic and applied research, is the need to use acidified water for solubilization. To overcome this problem, the elicitor effect of water-soluble COS on the biosynthesis of both xanthones and volatile organic compounds (VOCs) was evaluated in the present study. The analysis of xanthones and VOCs was performed by HPLC and GC-MS headspace analysis. The obtained results showed that COS are very effective in enhancing xanthone biosynthesis. With 400mgL-1 COS, a xanthone content of about 30mgg-1 DW was obtained. The antifungal activity of extracts obtained with 400mgL-1 COS was the highest, with MIC50 of 32µgmL-1 against Candida albicans and 32-64µg mL-1 against dermatophytes, depending on the microorganism. Histochemical investigations suggested the accumulation of isoprenoids in the secretory ducts of H. perforatum roots. The presence of monoterpenes and sesquiterpenes was confirmed by the headspace analysis. Other volatile hydrocarbons have been identified. The biosynthesis of most VOCs showed significant changes in response to COS, suggesting their involvement in plant-fungus interactions.

One-step procedure for enhancing the antibacterial and antioxidant properties of a polysaccharide polymer: Kojic acid grafted onto chitosan

The purpose of this work was to develop a nontoxic bioactive material based on a natural pyrone compound (kojic acid, KA) and chitosan oligosaccharides (COS). The bioactive material, chitosan oligosaccharide-N-kojic acid polymer (COS-N-KA), was prepared by one-step environmentally friendly approach. Then, the physicochemical properties and biological activities of COS-N-KA as a prepared water-soluble COS derivative were evaluated. The polymer was characterized by using UV–vis, FTIR, 1H NMR, and 13C NMR spectroscopy, Mw, PID, TGA, water solubility, hemolysis assay, and animal toxicity studies. Particularly, the antioxidant and antimicrobial assays revealed that COS-N-KA significantly enhanced the antimicrobial and antioxidant activities, which remarkably stronger than that of free COS and KA. Hence, the low hemolytic activity to human red blood cells, and nontoxic to female mice of SLAC KM strain made this novel polymer material a promising and effective compound for food and pharmaceutical industries.

Biosynthesis of chitosan-Oligosaccharides (COS) by non-aflatoxigenic Aspergillus sp. strain EGY1 DSM 101520: A robust biotechnological approach

Abstract Currently applied methodologies (acidic or enzymatic chitosanolysis) towards synthesis of Chitosan- Oligosaccharides (COS) are faced with some drawbacks that confine their potential in biotechnological applications. The present work addresses a novel tailored method as an alternate to biosynthesize COS. An empirical statistical-mathematical approach [Plackett-Burman. Design (PBD) followed by Box-Behnken design (BBD)] was employed to optimize COS biosynthesis by an endo -chitosanase non-aflatoxigenic producing Aspergillus sp. section Flavi strain EGY1 DSM 101520 whole cells. Optimal levels localized by BBD for three key determinants were 0.687% (w/v) low molecular weight chitosan (LMWC), 25 °C incubation temperature and 72–96 h incubation time, along with 2.0 gL −1 maximal level of COS, achieving 94.7% model adequacy upon growing the fungus on LMWC-based tap water medium [merely 0.687% (w/v) LMWC]. Batch mode scaling up in the laboratory scale fermenter achieved 5.34 gL −1 of COS after 44 h with 2.67 fold enhancement. Partially acetylated hetero-oligomers with DPs (2–11) of the water-soluble COS were proved by TLC, MALDI-TOF-MS, 1 H NMR, 13 C NMR and FTIR. To the best of the authors' knowledge, the present work is the first study highlighting a novel, robust, cheap, environmentally safe, reproducible approach to biosynthesize COS by fungal whole cells.

Dual-functional bone implants with antibacterial ability and osteogenic activity.

A growing number of biomaterial-associated infections cause bone implant failures in early and long-term applications. In this regard, a calcium silicate-gelatine composite bone implant with high strength and superior osteogenic activity was coated with a layer of Ag, chitosan polysaccharide (CS) or water-soluble chitosan oligosaccharide (COS) as a bactericidal agent. The influences of surface modifications to the bone implants on phase composition, microstructure, antibacterial effectiveness, and osteogenic activity in vitro were evaluated. Experimental results revealed the presence of the coating on the implant surface using a simple deposition technique. The in vitro antibacterial evaluation indicated that the antimicrobial effectiveness of the Ag coating against Gram-positive Staphylococcus aureus (S. aureus) and Gram-negative Escherichia coli (E. coli) was inferior to the 0.4% CS coating, but comparable to those of 0.2% CS and 0.4% COS coatings after 48 h of culture. CS presented a greater bactericidal effect than COS, which was bacteria-independent. CS and COS coatings had no significant cytotoxicity towards L929 cells at coating concentrations of 0.1%, 0.2%, and 0.4%, except for the cells exposed to the 0.4% CS coating, while the 0.004% Ag coating remarkably produced cytotoxicity. The assays of cell functions consistently showed significantly higher osteogenic activity of MG63 cells grown on CS and COS-coated surfaces by increased attachment, proliferation, alkaline phosphatase, osteocalcin, and calcium deposits production, except for the 0.4% CS coating, in comparison with those on the Ag coated surface. It was concluded that, taking antibacterial ability and osteogenic activity into account, 0.2% CS-coated and 0.4% COS-coated calcium silicate-gelatine composite bone implants had a large potential to be used in bone grafts and fracture fixation devices.

Preparation and characterization of pH-sensitive camptothecin-cis-aconityl grafted chitosan oligosaccharide nanomicelles

Camptothecin (CPT) was introduced to water-soluble chitosan oligosaccharide (CHO) using cis-aconityl (CA), as a pH-sensitive linker, to develop a new hydrophobic structure, i.e. CPTCACHO. The triple conjugates were synthesized in three ratios (5%, 7.5%, and 10%) and characterized by Fourier transform infrared (FT-IR) and proton nuclear magnetic resonance (1HNMR). Thermo gravimetric analysis and critical micelle concentration (CMC) assessments were performed. Prepared nano-micelles were analyzed for particle size, polydispersity index (PDI), drug release and in vitro cytotoxicity. CPTCACHO 7.5% micelles as optimum micelles had a mean diameter of 50nm (observed by transmission electron microscopy), a zeta potential of +45.9mV, and a CMC of about 9.97×10−5g/L. The release results showed that CPTCACHO 7.5% has the burst release at acidic pH, and cytotoxicity study indicated that IC50 of CPTCACHO 7.5% for MCF-7 cell line was 0.8μg/mL. These properties altogether make CPTCACHO micelles, as a pH sensitive cargo with inherent cytotoxicity, a potential candidate for hydrophobic anticancer drugs.

Use of a Natural Compound Made of <i>Ecklonia bicyclis</i> Seaweed, <i>Tribulus terrestris</i> and Water-Soluble Chitosan Oligosaccharide, in Male Sexual Asthenia with Mild or Mild-Moderate Erectile Dysfunction and Serum Testosterone Levels at the Lower Limit of Normal

Objectives: to evaluate the effectiveness of a natural compound made of Ecklonia bicyclis Seaweed, Tribulus terrestris and water-soluble chitosan oligosaccharide, in the male sexual asthenia with mild or mild-moderate erectile dysfunction and serum testosterone levels between 280 and 350 ng/dl. Materials and Methods: 84 male patients affected by reduced libido and serum testosterone levels at the lower limit of normal, were recruited. We have separated patients in three different age groups: group A (18 - 45 years), group B (45 - 59 years), group C (>60 years). All subjects answered the International index of erectile function questionnaire (IIEF-5) and underwent determination of serum total testosterone before and after 30 days of treatment. Results: Before treatment, the group A showed mean (± standard deviation) total testosterone 321.9 ± 19.2 ng/dl and mean IIEF-5 18.6 ± 1.97, in the group B it was 318.5 ± 18.1 ng/dl and 16.3 ± 2.66, and finally in the group C it was 305.4 ± 13.1 ng/dl and 14.2 ± 1.95 respectively. After treatment mean total testosterone and mean IIEF-5 were respectively: group A (448 ± 111.46 ng/dl and 21.84 ± 3.41); group B (453.8 ± 105.23 ng/dl and 20.4 ± 3.81); group C (385.8 ± 87.29 ng/dl and 16.7 ± 3.84). Conclusions: The treatment with Ecklonia bicyclis, Tribulus terrestris and water-soluble chitosan oligosaccharide might represent a safe and effective option on the improvement of libido and erectile function in man with testosterone level at the lower limit of normal.

Preferential tumor accumulation and desirable interstitial penetration of poly(lactic-co-glycolic acid) nanoparticles with dual coating of chitosan oligosaccharide and polyethylene glycol-poly(d,l-lactic acid)

Despite advances in polymeric nanoparticles (NPs) as effective delivery systems for anticancer drugs, rapid clearance from blood and poor penetration capacity in heterogeneous tumors still remain to be addressed. Here, a dual coating of poly (ethylene glycol)-poly (d,l-lactic acid) (PEG-PDLLA) and water-soluble chitosan oligosaccharide (CO) was used to develop PLGA-based NPs (PCPNPs) with colloidal stability for delivery of paclitaxel (PTX). The PCPNPs were prepared by a modified nanoprecipitation process and exhibited homogeneous size of 165.5nm, and slight positive charge (+3.54mV). The single PEG-PDLLA-coated PLGA NPs (PPNPs) with negative charge (−13.42mV) were prepared as control. Human breast cancer MDA-MB-231 cell and mice MDA-MB-231 xenograft model were used for in vitro and in vivo evaluation. Compared to Taxol®, both PCPNPs and PPNPs increased the intracellular uptake and exerted stronger inhibitory effect on tumor cells in vitro, especially for PCPNPs. Particularly, due to the near neutral surface charge and shielding by the dual coating, the blank cationic NP presented low cytotoxicity. With the synergistic action of PEG-PDLLA and CO, PCPNPs not only strongly inhibited macrophage uptake and extended the blood circulation time, but also improved the selective accumulation and interstitial penetration capacity to/in tumor site. Consequently, a significantly enhanced antitumor efficacy was observed for the cationic PCPNPs. Our findings suggest that, the dual PEG-PDLLA/CO coating can effective improve the tumor accumulation and interstitial penetration of NPs and, therefore may have great potential for tumor treatment. Statement of significanceRapid clearance from blood and poor penetration capacity in heterogeneous tumors represent great challenge for polymeric nanoparticles (NPs) as effective delivery systems for anticancer drugs. This study provides a promising cationic nanoparticle (PCPNPs) with dual coating of chitosan oligosaccharide (CO) and PEG-PDLLA to address the above problem. The PCPNPs prepared with 165.5nm and slight positive charge (+3.54mV) showed an improved accumulation and interstitial penetration capacity to/in tumor site, and thus led to an enhanced antitumor efficacy. This is the first time to report the cooperative effect of PEG-PDLLA and CO on PLGA NPs in this field. This work can arouse broad interests among researchers in the fields of nanomedicine, nanotechnology, and drug delivery system.

Synthesis, Characterization, and Antimicrobial Activity of Kojic Acid Grafted Chitosan Oligosaccharide

A novel water-soluble chitosan oligosaccharide (COS) derivative, chitosan oligosaccharide/kojic acid grafts assigned as COS/KA, was prepared by using the selective partial alkylation of N-benzylidene COS and chlorokojic acid in the presence of dimethyl sulfoxide (DMSO) and pyridine (Py). The derivative was characterized by UV-vis spectroscopy, FTIR, (1)H NMR, TGA, SEM, and XRD techniques, which showed that the alkylation reaction took place at the C-6 and C-3 positions of COS. The results showed that the degree of substitution (DS) for COS/KA was from 0.38 to 1.21, and the product exhibited an excellent solubility in organic solvents and distilled water. The antibacterial results indicated that the antibacterial activity of COS/KA was strengthened relative to COS with the increase of DS for Staphylococcus aureus , Escherichia coli , Aspergillus niger and Saccharomyces cerevisiae . These findings provide important supports for developing new antibacterial agents and expand the scope of application of COS in the food industry.

A facile fabrication of porous PMMA as a potential bone substitute

This study is aimed to develop porous poly(methyl methacrylate) (PMMA) as a potential bone substitute via a facile fabrication method. Composites consisting of water-soluble chitosan oligosaccharide (CSO) and PMMA were prepared by combining freeze-drying with radical polymerization. Open porous PMMA with controlled porosities were obtained after the CSO was extracted gradually from the composites. The CSO aqueous solutions with different concentrations were frozen and then freeze-dried to obtain interconnected porous framework. Methyl methacrylate with initiators and a crosslink agent was introduced into the porous framework and polymerized, resulting in two-continuous phase composites. The mechanical properties of the initial composites and porous materials after immersion in PBS for 8 weeks were investigated. Dynamic mechanical analysis was conducted to study the mechanical strength of the composite, compared with bulk PMMA. Porosity and morphology of porous PMMA were studied using the liquid displacement method and scanning electron microscopy, respectively. Thermogravimetric analysis indicated that composite exhibited better thermal stability than bulk PMMA. The composites became porous materials after extracting bioactive CSO component. The mechanical properties of porous materials were closer to those of cancellous bone. The generation of pores using CSO seems to be a promising method to prepare porous PMMA as a potential bone substitute.