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Lactobionic acid is a comparatively less explored lactose derivative with impressive biofunctional qualities, and is currently being used by the advanced chemical and pharmaceutical research industries. It is an aldonic acid with probiotics, antimicrobial, antioxidant, calcium chelating activity. In dairy and food products, it can be used to improve flavor, texture, yield and shelf life with additional health benefits. The biochemical method for producing lactobionic acid makes it safe for humans to consume as food or medicine. This systematic review describes the various bioproduction methods of lactobionic acid. This study emphasizes the production method, conversion rate, and specific yield of various microorganisms and enzymes employed in biosynthesis of lactobionic acid. Scopus advanced search is used for database mining. Original, traceable peer-reviewed research articles directly related to lactobionic acid are selected for this systematic review. The selected articles are grouped for ease of discussion and understanding. In the last 75 years, several bioproduction methods of lactobionic acid have been developed. By fine-tuning the microbial incubation conditions, the productivity of lactobionic acid can be significantly improved. The oxidoreductase enzymes responsible for the conversion of lactose can be purified from the system by advanced membrane technology. In the presence of a suitable redox mediator and regenerative enzyme, an efficient continuous lactobionic acid production system can be developed. To date, several methods are available for the complete conversion of lactose to lactobionic acid with an impressive specific production rate. This review will help researchers and industries to have better insights and understanding of the bioproduction of lactobionic acid. [ABSTRACT FROM AUTHOR]

In this study, we introduce a novel experimental approach and present a simplified mathematical model for a quick monitoring of a biotec process producing lactobionic acid (LBA). It relies on monitoring the electrical conductivity of the fermentation broth and it is designed to predict the concentration of LBA throughout the microbial cheese whey valorization via LBA production. Following a systematic series of experiments conducted to refine the mathematical model, we performed conductivity monitoring during LBA production from "caciotta" and "squacquerone" wheys by Pseudomonas taetrolens in a 3 L stirred tank bioreactor. Throughout the bioproduction process, the conductivity values exhibited an upward trend corresponding to the increase in LBA concentration. Our findings underscore the feasibility and advantages of employing inline conductivity monitoring during LBA production from various cheese wheys. The results emphasize that conductivity measurements can effectively estimate product concentration in a fermentation process, particularly when there is a shift in ionic concentration. Furthermore, these conductivity measurements offer valuable insights for monitoring and optimizing the working conditions in a fermentation process. [ABSTRACT FROM AUTHOR]

Abstract Hepatocellular cancer (HCC) remained a life-threatening carcinoma. Agents for HCC imaging and therapy were expected to possess different intratumoral retention time. To construct an agent with different intratumoral retention time when applied for tumor imaging or therapy remained great values. A lasialoglycoprotein receptor (ASGPR) targeted lactobionic acid derivative (LABO) was constructed for fluorescent imaging and photodynamic therapy of HCC. 18F labeled LABO (18F-LABO) was developed for PET imaging of HCC. LABO and 18F-LABO showed similar molecular structure. LABO exhibited characteristic of viscosity and concentration-induced intratumoral in-situ self-assembly to expand the intratumoral retention. LABO was non-fluorescent at free stage, but emitted NIR fluorescence and generated irradiation-induced ROS after self-assembly for fluorescent imaging and photodynamic therapy. ASGPR specificity of LABO and 18F-LABO was confirmed using HepG2 cell. Biodistribution and fluorescent imaging confirmed the different tumor retention time of LABO and 18F-LABO when used for photodynamic therapy and PET imaging. PET imaging and photodynamic therapy were performed on HepG2 tumor bearing mice, which revealed that 18F-LABO/LABO could specifically accumulated in the HepG2 tumor for tumor location/inhibition. LABO/18F-LABO with excellent HCC specificity but different intratumoral behaviors showed great values for the PET/NIR imaging and photodynamic therapy for HCC. Graphical Abstract

The aim of this study was to quantitatively analyse lactobionic acid obtained from bioreactor cultures using whey as a liquid medium with bacteria of the Pseudomonas taetrolens species. The most important culture parameters affecting the production of the acid are indicated and evaluated. The highest lactobionic acid yield was 37.42 g/L, selecting the appropriate strain (Pseudomonas taetrolens 4′) and environmental conditions (2% lactose concentration in the bioreactor). The amount of lactose and lactobionic acid was determined by high-performance liquid chromatography. Microorganism analysis was also carried out using a flow cytometer with imaging to study the metabolic activity of microorganisms during lactobionic acid production. In addition, during the study, Bifidobacteria were microencapsulated with lactobionic acid and their survival was evaluated in an in vitro model of the gastrointestinal tract, checking the prebiotic properties of the acid. The highest number of viable cells in the microcapsules after digestion was obtained using the Bifidobacterium bifidum strain DSM 20082. The antagonistic activity of lactobionic acid was also analysed. [ABSTRACT FROM AUTHOR]

Simple Summary: Lactobionic acid (Lba) has been found to have a range of health-promoting benefits and practical applications across various fields, including agriculture. However, the impact of Lba on the chemical composition and nutritional quality of eggs from early laying hens has been largely overlooked. The incorporation of Lba into the diet has been observed to elevate the content of monounsaturated fatty acids (MUFAs), specifically palmitoleic and vaccenic acids. In summary, as a functional product, Lba has the potential to improve the productivity of laying hens and enhance the nutritional value of eggs during the early laying period. Lactobionic acid (Lba), an oligosaccharide aldonic acid, has demonstrated various health-promoting benefits and applications in diverse areas. Lba has been recognized for its multifunctional properties, such as metal ion chelation and calcium sequestration. This study aimed to evaluate the effects of supplementing the diet of early-laying hens with Lba (EXP group) on their performance and the physical–chemical properties, and nutritional quality of eggs. The 12-week study involved 700 Sonja breed hens per group, with the EXP group's diet enriched with 2% of biotechnologically produced Lba, while the control group (CON) received no Lba supplementation. Lba supplementation influenced both the hen's performance and egg quality, particularly in terms of egg production and fatty acid accumulation. Performance in the EXP group was significantly improved (p < 0.05), showing a 4.6–8.9% increase compared to the CON group at all experiment stages. Lba also promoted an increase in monounsaturated fatty acid (MUFA) content, particularly palmitoleic and vaccenic acids. Overall, Lba supplementation enhanced both the productivity of laying hens and the nutritional value of eggs during the early laying period. [ABSTRACT FROM AUTHOR]

Hepatocellular cancer (HCC) remained a life-threatening carcinoma. Agents for HCC imaging and therapy were expected to possess different intratumoral retention time. To construct an agent with different intratumoral retention time when applied for tumor imaging or therapy remained great values. A lasialoglycoprotein receptor (ASGPR) targeted lactobionic acid derivative (LABO) was constructed for fluorescent imaging and photodynamic therapy of HCC. 18F labeled LABO (18F-LABO) was developed for PET imaging of HCC. LABO and 18F-LABO showed similar molecular structure. LABO exhibited characteristic of viscosity and concentration-induced intratumoral in-situ self-assembly to expand the intratumoral retention. LABO was non-fluorescent at free stage, but emitted NIR fluorescence and generated irradiation-induced ROS after self-assembly for fluorescent imaging and photodynamic therapy. ASGPR specificity of LABO and 18F-LABO was confirmed using HepG2 cell. Biodistribution and fluorescent imaging confirmed the different tumor retention time of LABO and 18F-LABO when used for photodynamic therapy and PET imaging. PET imaging and photodynamic therapy were performed on HepG2 tumor bearing mice, which revealed that 18F-LABO/LABO could specifically accumulated in the HepG2 tumor for tumor location/inhibition. LABO/18F-LABO with excellent HCC specificity but different intratumoral behaviors showed great values for the PET/NIR imaging and photodynamic therapy for HCC. [ABSTRACT FROM AUTHOR]

Background/Objectives: Nasal vaccines are a promising strategy for enhancing mucosal immune responses and preventing diseases at mucosal sites by stimulating the secretion of secretory IgA, which is crucial for early pathogen neutralization. However, designing effective nasal vaccines is challenging due to the complex immunological mechanisms in the nasal mucosa, which must balance protection and tolerance against constant exposure to inhaled pathogens. The nasal route also presents unique formulation and delivery hurdles, such as the mucous layer hindering antigen penetration and immune cell access. Methods: This review focuses on cutting-edge approaches to enhance nasal vaccine delivery, particularly those targeting C-type lectin receptors (CLRs) like the mannose receptor and macrophage galactose-type lectin (MGL) receptor. It elucidates the roles of these receptors in antigen recognition and uptake by antigen-presenting cells (APCs), providing insights into optimizing vaccine delivery. Results: While a comprehensive examination of targeted glycoconjugate vaccine development is outside the scope of this study, we provide key examples of glycan-based ligands, such as lactobionic acid and mannose, which can selectively target CLRs in the nasal mucosa. Conclusions: With the rise of new viral infections, this review aims to facilitate the design of innovative vaccines and equip researchers, clinicians, and vaccine developers with the knowledge to enhance immune defenses against respiratory pathogens, ultimately protecting public health. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus biofilm is a common bio-contaminant source that leads to food cross-contamination and foodborne disease outbreaks. Hence, there is a need for searching novel antibiofilm agents with potential anti-virulence properties to control S. aureus contamination and infections in food systems. In this study, the antibiofilm effects of lactobionic acid (LBA) against S. aureus and its influence on virulence were explored. The minimum inhibition concentration of LBA on S. aureus was 8 mg/mL. Viable count and crystal violet assays revealed that LBA inhibited and inactivated S. aureus biofilms. Microscopic observations further confirmed the antibiofilm activity of LBA on S. aureus that disrupted the biofilm architecture and inactivated the viable cells in biofilms. Moreover, LBA decreased the release of extracellular DNA (eDNA) and extracellular polysaccharide (EPS) in S. aureus biofilms. LBA suppressed biofilm formation by intervening metabolic activity and reduced virulence secretion by repressing the hemolytic activity of S. aureus. Furthermore, LBA altered the expressions of biofilm- and virulence-related genes in S. aureus, further confirming that LBA suppressed biofilm formation and reduced the virulence secretion of S. aureus. The results suggest that LBA might be useful in preventing and controlling biofilm formation and the virulence of S. aureus to ensure food safety. [ABSTRACT FROM AUTHOR]

Anna Ko&lstrok;odziejczak, Helena Rotsztejn Department of Cosmetology and Aesthetic Dermatology, Medical University of Lód&zacute;, &Lstrok;ód&zacute;, PolandCorrespondence: Anna Ko&lstrok;odziejczak, Email anna.kolodziejczak@umed.lodz.plObjective: Particular attention is given to the enhancement of melanin-related pigmentation (dark circles, photoaging) and vascular circles, which are commonly located in the tear trough. The objective of the study is to provide an objective evaluation of the impact of carboxytherapy and the treatment regimen combining carboxytherapy with lactobionic acid (20%, pH 2.1) or ferulic acid (14%, pH 4.0– 5.0) and ascorbic acid (12%) on skin defects in the eye area.Materials and Methods: A group of 39 Caucasian people were subjected to a series of five carboxytherapy treatments (right eye area) and five treatments combining carboxytherapy with a selected chemical peel for the skin around the eyes (left eye area). The efficacy of therapy was assessed based on parameters (MI and EI) measured with the Mexameter probe. Measurements were made in the tear trough and the middle of the lower eyelid.Results: We demonstrated that a series of carboxytherapy (right side) significantly statistically influenced the EI parameter (in different measurement points: P < 0.0001, P = 0.015, P = 0.002), which reflects the intensity of vascular circles under the eyes. Improvement of this parameter by 7.2 units was also shown in the tear trough in 82.1% of participants after the application of carboxytherapy combined with acids (left side) on the valley of tears for this parameter (EI). Lactobionic acid and carboxytherapy were associated with a statistically significant improvement (P = 0.011) in the tear trough. In this study, a reduction in the combined pigmentation (MI plus EI) for both the right and left sides (p = 0.001 and p = 0.015, respectively) was observed.Conclusion: The study provides objective evidence for the effectiveness of sole carboxytherapy and carboxytherapy combined with acids in the reduction of dark circles, in particular vascular circles in the tear trough. Lactobionic acid, ferulic acid, and ascorbic acid can be used as safe supplements to enhance carboxytherapy.Keywords: carboxytherapy, dark circles, lactobionic acid, ferulic acid, ascorbic acid

Abstract In this study, lactobionic acid (LBA) was incorporated into poly(vinyl alcohol) (PVA) and poly(ε-caprolactone) (PCL) by electrospinning. The antimicrobial effects of the nanofibers were tested using the agar diffusion method. Only the PVA formulations showed antimicrobial activity against Staphylococcus aureus. The PVA and PCL nanofibers containing LBA showed antioxidant activity ranging from 690.33 to 798.67 µM TEAC when tested by the ABTS method. The characterization of nanofibers was performed by scanning electron microscopy, Fourier transform infrared spectroscopy, thermogravimetric analysis, differential scanning calorimetry, and mechanical analysis. The nanofibers showed a uniform morphology and their average diameters ranged from 295.5 to 2778.2 nm. The LBA addition induced a decrease in the enthalpy of fusion (ΔHm) of PVA and PCL nanofibers, while the Young’s modulus was reduced from 20 to 10 MPa in PCL and PCL-LBA nanofibers, respectively. No relevant differences were observed between the FTIR spectra of the control nanofibers and the nanofibers containing LBA. All nanofibers presented hemolysis rate below 2%, thus can be considered as non-hemolytic materials. Further toxicological assessment was performed with the selected formulation PVA10 + LBA. The evaluations by mutagenicity assay, cell survival measurement, cell viability analysis and agar diffusion cytotoxicity test indicated that there are no significant toxic effects. Electrospun nanofibers PVA-LBA and PCL-LBA were successfully produced, showing good thermal and mechanical properties and non-toxic effects. Furthermore, the nanofibers showed antimicrobial activity and antioxidant activity. The findings of this study indicate that PVA and PCL electrospun nanofibers incorporating LBA are promising for use in packaging applications.

In this study, lactobionic acid (LBA) was incorporated into poly(vinyl alcohol) (PVA) and poly(ε-caprolactone) (PCL) by electrospinning. The antimicrobial effects of the nanofibers were tested using the agar diffusion method. Only the PVA formulations showed antimicrobial activity against Staphylococcus aureus. The PVA and PCL nanofibers containing LBA showed antioxidant activity ranging from 690.33 to 798.67 µM TEAC when tested by the ABTS method. The characterization of nanofibers was performed by scanning electron microscopy, Fourier transform infrared spectroscopy, thermogravimetric analysis, differential scanning calorimetry, and mechanical analysis. The nanofibers showed a uniform morphology and their average diameters ranged from 295.5 to 2778.2 nm. The LBA addition induced a decrease in the enthalpy of fusion (ΔHm) of PVA and PCL nanofibers, while the Young's modulus was reduced from 20 to 10 MPa in PCL and PCL-LBA nanofibers, respectively. No relevant differences were observed between the FTIR spectra of the control nanofibers and the nanofibers containing LBA. All nanofibers presented hemolysis rate below 2%, thus can be considered as non-hemolytic materials. Further toxicological assessment was performed with the selected formulation PVA10 + LBA. The evaluations by mutagenicity assay, cell survival measurement, cell viability analysis and agar diffusion cytotoxicity test indicated that there are no significant toxic effects. Electrospun nanofibers PVA-LBA and PCL-LBA were successfully produced, showing good thermal and mechanical properties and non-toxic effects. Furthermore, the nanofibers showed antimicrobial activity and antioxidant activity. The findings of this study indicate that PVA and PCL electrospun nanofibers incorporating LBA are promising for use in packaging applications. [ABSTRACT FROM AUTHOR]

The formulation of novel delivery protocols for the targeted delivery of genes into hepatocytes by receptor mediation is important for the treatment of liver-specific disorders, including cancer. Non-viral delivery methods have been extensively studied for gene therapy. Gold nanoparticles (AuNPs) have gained attention in nanomedicine due to their biocompatibility. In this study, AuNPs were synthesized and coated with polymers: chitosan (CS), and polyethylene glycol (PEG). The targeting moiety, lactobionic acid (LA), was added for hepatocyte-specific delivery. Physicochemical characterization revealed that all nano-formulations were spherical and monodispersed, with hydrodynamic sizes between 70 and 250 nm. Nanocomplexes with pCMV-Luc DNA (pDNA) confirmed that the NPs could bind, compact, and protect the pDNA from nuclease degradation. Cytotoxicity studies revealed that the AuNPs were well tolerated (cell viabilities > 70%) in human hepatocellular carcinoma (HepG2), embryonic kidney (HEK293), and colorectal adenocarcinoma (Caco-2) cells, with enhanced transgene activity in all cells. The inclusion of LA in the NP formulation was notable in the HepG2 cells, which overexpress the asialoglycoprotein receptor on their cell surface. A five-fold increase in luciferase gene expression was evident for the LA-targeted AuNPs compared to the non-targeted AuNPs. These AuNPs have shown potential as safe and suitable targeted delivery vehicles for liver-directed gene therapy. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is a malignant tumor that affects many patients diagnosed with hepatic cell inflammation and liver cirrhosis. Targeted polymeric nanocapsules could facilitate the internalization and accumulation of anticancer drugs. Dual-targeted folic acid/lactobionic acid-poly lactic co-glycolic acid nanocapsules (NCs) were prepared and loaded with pterostilbene (PTN) and characterized for their physicochemical properties, as well as in vitro and in vivo anticancer activity. NCs displayed a size of 222 nm, zeta potential of − 16.5 mV, and sustained release for 48 h. The IC50 of PTN NCs (5.87 ± 0.8 µg/mL) was 20 times lower than unencapsulated PTN (121.26 ± 9.42 µg/mL) on HepG2 liver cancer cells owing to the enhanced cellular uptake of the former, as delineated by flow cytometry. In vivo study on HCC-induced animals delineated the superiority of the dual-targeted NCs over the unencapsulated PTN, which significantly reduced the liver markers ALT, AST, and ALP, as well as the tumor-related markers AFP and Bcl2, and elevated the anti-apoptotic marker caspase 3. Furthermore, the NCs significantly reduced the oxidative stress and exhibited almost comparable histological features to the normal group. Therefore, it can be concluded that the dual-ligated folic acid/lactobionic acid nanocapsules can be considered a promising potential treatment option for hepatocellular carcinoma. [ABSTRACT FROM AUTHOR]

Recently, deep eutectic solvents (DESs) have attracted considerable interest in analytical chemistry. This work described the enantioseparations of twenty amino alcohol drugs with several DESs based on lactobionic acid (LA) as the sole chiral selector in capillary electrophoresis (CE) firstly. Compared to the single LA system and the ionic liquid/LA synergistic system, the DES system exhibited considerably improved separations. The influences of some key parameters on separations were investigated in detail. This work also experimentally demonstrated that the carboxyl group was indispensable in the process of chiral recognition. The mechanisms of the improvements of DESs on enantioseparations were studied via ultraviolet spectroscopy. Furthermore, the proposed method was used to determine the enantiomeric purity of propranolol hydrochloride successfully. This is the first time that chiral DESs were utilized as the sole chiral selectors in CE, and this strategy has opened up a new prospect for the use of DESs in enantioseparation. [ABSTRACT FROM AUTHOR]

We report a novel production process for lactobionic acid (LBA) production using an engineered Neurospora crassa strain F5. The wild-type N. crassa strain produces cellobiose dehydrogenase (CDH) and uses lactose as a carbon source. N. crassa strain F5, which was constructed by deleting six out of the seven β-glucosidases in the wild type, showed a much slower lactose utilization rate and produced a much higher level of cellobiose dehydrogenase (CDH) than the wild type. Strain N. crassa F5 produced CDH and laccase simultaneously on the pretreated wheat straw with 3 µM of cycloheximide added as the laccase inducer. The deproteinized cheese whey was added directly to the shake flasks with the fungus present to achieve LBA production. Strain F5 produced about 37 g/L of LBA from 45 g/L of lactose in 27 h since deproteinized cheese whey addition. The yield of LBA from consumed lactose was about 85%, and the LBA productivity achieved was about 1.37 g/L/h. [ABSTRACT FROM AUTHOR]

Yacon juice is a worthy alternative of a product able to keep all the benefits of the yacon roots. Lactobionic acid has been studied as a food functional acidifier, although still without permission to be applied in foods, cannot be sensory evaluated. Thus, the only approach to estimate a sensory profile of a lactobionic acid-added product is correlating sensory data with chemometric assessments. Sensory evaluation of yacon juice was performed with flash profile and its results were correlated with E-nose ones. Sensometrics showed a high similarity between yacon juice with lactobionic acid and tartaric acid regarding the volatile signals, and both raised the descriptors: Astringency, yellow color pearl-like, herbal, soy, cereal and leaf flavor, acid and bitter residual flavors. This study showed not just the potential of yacon juice as a new product, but also the suitability of combining flash profile and sensometrics to access a potential ingredient.

Staphylococcus aureus biofilm is a common bio-contaminant source that leads to food cross-contamination and foodborne disease outbreaks. Hence, there is a need for searching novel antibiofilm agents with potential anti-virulence properties to control S. aureus contamination and infections in food systems. In this study, the antibiofilm effects of lactobionic acid (LBA) against S. aureus and its influence on virulence were explored. The minimum inhibition concentration of LBA on S. aureus was 8 mg/mL. Viable count and crystal violet assays revealed that LBA inhibited and inactivated S. aureus biofilms. Microscopic observations further confirmed the antibiofilm activity of LBA on S. aureus that disrupted the biofilm architecture and inactivated the viable cells in biofilms. Moreover, LBA decreased the release of extracellular DNA (eDNA) and extracellular polysaccharide (EPS) in S. aureus biofilms. LBA suppressed biofilm formation by intervening metabolic activity and reduced virulence secretion by repressing the hemolytic activity of S. aureus. Furthermore, LBA altered the expressions of biofilm- and virulence-related genes in S. aureus, further confirming that LBA suppressed biofilm formation and reduced the virulence secretion of S. aureus. The results suggest that LBA might be useful in preventing and controlling biofilm formation and the virulence of S. aureus to ensure food safety.

Purpose: Since there is a lack of clear information regarding the benefit to combine supportive therapies (such as artificial tears) to mitomycin C (MMC) in the treatment of ocular surface neoplasia, the primary purpose of the study was to evaluate hyaluronic acid eye drops and hyaluronic acid-conjugated lactobionic acid (LACTOyal FREE) eye drops as supportive therapy. Methods: Retrospective evaluation of patients with ocular surface squamous neoplasia or conjunctival melanocytic tumor treated with MMC, who had used also artificial tears as supportive treatment. A 6-month follow-up with evaluation of subjective and objective tests for ocular surface integrity was conducted. Results: A total of 35 patients were analyzed, most of them with squamous disease (71.4%). The break-up time (BUT), Ocular Surface Disease Index (OSDI) and Schirmer test values showed a significant difference at any time point with overall population. No statistical difference was found among subgroups (Lactoyal vs No Lactoyal). Conclusion: The use of an ancillary therapy based on hyaluronic acid allows to improve both subjective and objective ocular parameters, reducing MMC induced adverse effects. Meantime, hyaluronic acid-conjugated lactobionic acid eye drops highlighted the same advantages with a more positive trend in OSDI results. [ABSTRACT FROM AUTHOR]

Lactobionic acid (LBA) is a bioactive compound that has become increasingly popular in medicine in recent years due to its unique properties. This chemical can be formed via the enzymatic oxidation of lactose using fungal oxidoreductive enzymes. This study aimed to intensify the synthesis of LBA using immobilised enzymes (cellobiose dehydrogenase from Phanerochaete chrysosporium (PchCDH) and laccase from Cerrena unicolor (CuLAC)) on chitosan microspheres. We used three different crosslinking agents: genipin, glutaraldehyde, and polyethyleneimine to activate the chitosan. The FTIR and CellDrop techniques were used to characterise the activated microspheres. Quantitative (HPLC) and qualitative (TLC) methods were used to determine the obtained LBA. The results show that the type of activator used influences the efficiency of the binding of the enzyme to the matrix. Furthermore, the amount of LBA formed depends on the type of system used. The use of a system in which one of the enzymes is immobilised on a PEI-activated carrier (PchCDH) and the other is free (CuLAC) proved to be the most optimal, as it yielded almost 100% conversion of lactose to lactobionic acid. Summarising the data obtained the following: lactobionic acid immobilised on chitosan microspheres has great potential for medical applications. [ABSTRACT FROM AUTHOR]

In this work, we synthesized lactobionic acid-decorated diselenide-linked polyethylene glycol-doxorubicin conjugate (LA-PEG-SeSe-DOX) and prepared free DOX-loaded LA-PEG-SeSe-DOX(DOX@LA-PEG-SeSe-DOX) nanoparticles for hepatoma-targeted DOX delivery. LA-PEG-SeSe-DOX can self-assemble into nanoparticles in deionized water and DOX@LA-PEG-SeSe-DOX nanoparticles were prepared by loading free DOX into LA-PEG-Se-Se-DOX nanoparticles under sonication. DOX@LA-PEG-SeSe-DOX nanoparticles have high DOX loading content of 31.3%. The dynamic scattering analysis shows that DOX@LA-PEG-SeSe-DOX nanoparticles have small size (hydrodynamic diameter 4 5. 6 9 ± 0. 7 1 nm), near neutral zeta potential, and excellent colloidal stability. The in vitro drug release study indicates that DOX@LA-PEG-SeSe-DOX nanoparticles exhibit dual redox-responsive drug release characteristics. The cellular uptake study reveals that DOX@LA-PEG-SeSe-DOX nanoparticles can be taken up by hepatoma cells by asialoglycoprotein receptor (ASGPR)-mediated pathway. Finally, DOX@LA-PEG-SeSe-DOX nanoparticles exhibit enhanced cytotoxicity against HepG2 cells as compared to LA-PEG-SeSe-DOX nanoparticles, underlining the significance of releasing free DOX for effective tumor cell proliferation inhibition. This work provides a facile and effective strategy for targeted delivery of DOX to hepatoma cells. [ABSTRACT FROM AUTHOR]

Zi Chao Wu,1,2,&ast; Xin Yu Liu,1,&ast; Jia Yan Liu,1 Jing Shu Piao,1 Ming Guan Piao1,3 1School of Pharmacy, Yanbian University, Yanji, 133002, People’s Republic of China; 2Research Institute, Shijiazhuang Yiling Pharmaceutical Co., Ltd, Shijiazhuang, 050035, People’s Republic of China; 3Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, Yanbian University, Yanji, 133002, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ming Guan Piao; Jing Shu Piao, Email mgpiao@ybu.edu.cn; piaojingshu@ybu.edu.cnAim: Liver fibrosis is mainly characterized by the formation of fibrous scars. Galactosylated chitosan (GC) has gained increasing attention as a liver-targeted drug carrier in recent years. The present study aimed to investigate the availability of betulinic acid-loaded GC nanoparticles (BA-GC-NPs) for liver protection. Covalently-conjugated galactose, recognized by asialoglycoprotein receptors exclusively expressed in hepatocytes, was employed to target the liver.Materials and Methods: Galactose was coupled to chitosan by chemical covalent binding. BA-GC-NPs were synthesized by wrapping BA into NPs via ion-crosslinking method. The potential advantage of BA-GC-NP as a liver-targeting agent in the treatment of liver fibrosis has been demonstrated in vivo and in vitro.Results: BA-GC-NPs with diameters < 200 nm were manufactured in a virtually spherical core-shell arrangement, and BA was released consistently and continuously for 96 h, as assessed by an in vitro release assay. According to the safety evaluation, BA-GC-NPs demonstrated good biocompatibility at the cellular level and did not generate any inflammatory reaction in mice. Importantly, BA-GC-NPs showed an inherent liver-targeting potential in the uptake behavioral studies in cells and bioimaging tests in vivo. Efficacy tests revealed that administering BA-GC-NPs in a mouse model of liver fibrosis reduced the degree of liver injury in mice.Conclusion: The findings showed that BA-GC-NPs form a safe and effective anti-hepatic fibrosis medication delivery strategy.Keywords: nanoparticles, lactobionic acid, chitosan, liver fibrosis, betulinic acid

Abstract Background Efficient upgrading of inferior agro-industrial resources and production of bio-based chemicals through a simple and environmentally friendly biotechnological approach is interesting Lactobionic acid is a versatile aldonic acid obtained from the oxidation of lactose. Several microorganisms have been used to produce lactobionic acid from lactose and whey. However, the lactobionic acid production titer and productivity should be further improved to compete with other methods. Results In this study, a new strain, Pseudomonas fragi NL20W, was screened as an outstanding biocatalyst for efficient utilization of waste whey to produce lactobionic acid. After systematic optimization of biocatalytic reactions, the lactobionic acid productivity from lactose increased from 3.01 g/L/h to 6.38 g/L/h in the flask. In batch fermentation using a 3 L bioreactor, the lactobionic acid productivity from whey powder containing 300 g/L lactose reached 3.09 g/L/h with the yield of 100%. Based on whole genome sequencing, a novel glucose dehydrogenase (GDH1) was determined as a lactose-oxidizing enzyme. Heterologous expression the enzyme GDH1 into P. putida KT2440 increased the lactobionic acid yield by 486.1%. Conclusion This study made significant progress both in improving lactobionic acid titer and productivity, and the lactobionic acid productivity from waste whey is superior to the ever reports. This study also revealed a new kind of aldose-oxidizing enzyme for lactose oxidation using P. fragi NL20W for the first time, which laid the foundation for further enhance lactobionic acid production by metabolic engineering. Graphical Abstract

Enzymes produced by white rot fungi are involved in the synthesis of secondary metabolites with valuable biotechnological properties. One of these metabolites is lactobionic acid (LBA). The aim of this study was to characterize a novel enzyme system consisting of a cellobiose dehydrogenase from Phlebia lindtneri (PlCDH), a laccase from Cerrena unicolor (CuLAC), a redox mediator (ABTS or DCPIP), and lactose as a substrate. We used quantitative (HPLC) and qualitative methods (TLC, FTIR) to characterise the obtained LBA. The free radical scavenging effect of the synthesised LBA was assessed with the DPPH method. Bactericidal properties were tested against Gram-negative and Gram-positive bacteria. We obtained LBA in all the systems tested; however, the study showed that the temperature of 50 °C with the addition of ABTS was the most advantageous condition for the synthesis of lactobionic acid. A mixture with 13 mM LBA synthesised at 50 °C with DCPIP showed the best antioxidant properties (40% higher compared with the commercial reagent). Furthermore, LBA had an inhibitory effect on all the bacteria tested, but the effect was better against Gram-negative bacteria with growth inhibition no lower than 70%. Summarizing the obtained data, lactobionic acid derived in a multienzymatic system is a compound with great biotechnological potential. [ABSTRACT FROM AUTHOR]

Simple Summary: The European food industry creates millions of tons of waste products annually that are discarded or utilized inefficiently. The goals set in European legislation have been pivotal drivers in enhancing waste management and stimulating innovation in recycling. Without innovations in processing technologies, the quantity of waste will steadily rise. Considering the evidence of lactobionic acid's (Lba) health-promoting benefits and already established protocol for whey lactose conversion via microbial cultures developed by a group from Latvia University of Life Sciences and Technologies LBTU, the current study aimed to elucidate the effect of the supplementation of dairy cows' diets with biotechnologically obtained Lba-rich whey on animals' performances and milk quality traits. The acquired results revealed that produced Lba could be deemed an alternative to sugar beet molasses to supplement the diet of dairy cows and positively influence the composition of essential amino acids and polyunsaturated fatty acids. The use of Lba in the diet of dairy cows during the lactation period equal to molasses affected the cows' performances and milk quality traits, especially fat composition. Dairy processing is one of the most polluting sectors of the food industry as it causes water pollution. Given considerable whey quantities obtained via traditional cheese and curd production methods, manufacturers worldwide are encountering challenges for its rational use. However, with the advancement in biotechnology, the sustainability of whey management can be fostered by applying microbial cultures for the bioconversion of whey components such as lactose to functional molecules. The present work was undertaken to demonstrate the potential utilization of whey for producing a fraction rich in lactobionic acid (Lba), which was further used in the dietary treatment of lactating dairy cows. The analysis utilizing high-performance liquid chromatography with refractive index (HPLC-RID) detection confirmed the abundance of Lba in biotechnologically processed whey, corresponding to 11.3 g L−1. The basic diet of two dairy cow groups involving nine animals, Holstein Black and White or Red breeds in each, was supplemented either with 1.0 kg sugar beet molasses (Group A) or 5.0 kg of the liquid fraction containing 56.5 g Lba (Group B). Overall, the use of Lba in the diet of dairy cows during the lactation period equal to molasses affected cows' performances and quality traits, especially fat composition. The observed values of urea content revealed that animals of Group B and, to a lesser extent, Group A received a sufficient amount of proteins, as the amount of urea in the milk decreased by 21.7% and 35.1%, respectively. After six months of the feeding trial, a significantly higher concentration of essential amino acids (AAs), i.e., isoleucine and valine, was observed in Group B. The percentage increase corresponded to 5.8% and 3.3%, respectively. A similar trend of increase was found for branched-chain AAs, indicating an increase of 2.4% compared with the initial value. Overall, the content of fatty acids (FAs) in milk samples was affected by feeding. Without reference to the decrease in individual FAs, the higher values of monounsaturated FAs (MUFAs) were achieved via the supplementation of lactating cows' diets with molasses. In contrast, the dietary inclusion of Lba in the diet promoted an increase in saturated FA (SFA) and polyunsaturated FA (PUFA) content in the milk after six months of the feeding trial. [ABSTRACT FROM AUTHOR]

Background: Actually, the use of chemical peels in cosmetics and dermatology continues to grow due to their versatility, clinical endpoint–directed predictability, and favorable risk profile in comparison to lasers. The chemical peel is a generally safe method for treatment of some skin disorders and to refresh and rejuvenate the skin. The major challenge of chemical peels is the tolerability, that is because of sensitive skin which is one of the most common skin disorders. Aim: The aim of this study was to evaluate the effectiveness of the new Miamo Renewal Peel Serum formulated with a pool of new generation acids (ELPA25™) on sensitive skin with respect to mandelic acid serum only and with respect to placebo comparison. Materials and Methods: The "in vivo" study following the half‐face experimental protocol active versus placebo involved 30 healthy Caucasian female volunteers between 25 and 64 years, with sensitive skin, who were divided into two different groups. ELPA25™ serum was applied in one group three times a week for 8 weeks. The other group, with the same protocol, applied an active serum containing mandelic acid, as control, versus placebo. In particular, skin moisturizing, skin viscoelastic properties, skin surface smoothness, wrinkle reduction, and stratum corneum renewal were evaluated. Results: Renewal Peel Serum was very well tolerated from sensitive skin. A significant decrease in skin roughness and wrinkle breadth, and an improvement in firmness and in skin elasticity, was observed after 2 months of treatment with respect both to mandelic acid serum and to placebo comparison. Conclusions: Scientific protocol using self‐controlled study methodology and noninvasive skin bioengineering techniques with adequate statistical methods were able to evaluate both the safety and the efficacy of the new Miamo Renewal Peel Serum. This study highlighted that the Miamo Renewal Peel Serum formulated with a patent‐pending mixture of new generation acids (ELPA25™) exerts many beneficial effects and it can be successfully employed for sensitive skin. [ABSTRACT FROM AUTHOR]

Background: Efficient upgrading of inferior agro-industrial resources and production of bio-based chemicals through a simple and environmentally friendly biotechnological approach is interesting Lactobionic acid is a versatile aldonic acid obtained from the oxidation of lactose. Several microorganisms have been used to produce lactobionic acid from lactose and whey. However, the lactobionic acid production titer and productivity should be further improved to compete with other methods. Results: In this study, a new strain, Pseudomonas fragi NL20W, was screened as an outstanding biocatalyst for efficient utilization of waste whey to produce lactobionic acid. After systematic optimization of biocatalytic reactions, the lactobionic acid productivity from lactose increased from 3.01 g/L/h to 6.38 g/L/h in the flask. In batch fermentation using a 3 L bioreactor, the lactobionic acid productivity from whey powder containing 300 g/L lactose reached 3.09 g/L/h with the yield of 100%. Based on whole genome sequencing, a novel glucose dehydrogenase (GDH1) was determined as a lactose-oxidizing enzyme. Heterologous expression the enzyme GDH1 into P. putida KT2440 increased the lactobionic acid yield by 486.1%. Conclusion: This study made significant progress both in improving lactobionic acid titer and productivity, and the lactobionic acid productivity from waste whey is superior to the ever reports. This study also revealed a new kind of aldose-oxidizing enzyme for lactose oxidation using P. fragi NL20W for the first time, which laid the foundation for further enhance lactobionic acid production by metabolic engineering. [ABSTRACT FROM AUTHOR]

Cancer cells are under oxidative stress associated with the increased generation of reactive oxygen species (ROS). Therefore, increasing the oxidative stress of tumor cells by delivering ROS generators is an effective strategy to induce apoptosis of cancer cells. Herein, we reported a hybrid nanoparticle based on lactobionic acid (LA) modified chitosan and cinnamaldehyde (CA) modified chitosan, which possesses both active tumor-targeting ability and ROS regulation ability, in order to have a synergistic effect with the anti-tumor drug doxorubicin (DOX). LA can improve the tumor-targeting ability and cellular accumulation of these nanoparticles, and CA can induce apoptotic cell death through ROS generation, mitochondrial permeability transition and caspase activation. The particle size and distribution as well as drug release profiles of these nanoparticles were observed. In vitro and in vivo antitumor studies demonstrated that the hybrid nanoparticles show a significant synergistic antitumor effect. Thus, we anticipate that the hybrid nanoparticles have promising potential as an anticancer drug carrier.

Traditional cheese is the main milk derivative in Bénin. This traditional process is not efficient and generate a lot of whey which has no real use until now. It is just disposed without being environmentally treated. Its use as a source for lactobionic and lactic acids production by Pseudomonas taetrolens and Lactobacillus casei is studied in this work, being also a proposal that can greatly boost economically the dairy sector in the country and reduce the end-of-cycle impact of the residue. To our knowledge, no data is available in the metabolization of Bénin’s traditional cheese whey and its potential transformation into commercially valuable products such as lactobionic and lactic acids. With bulk filtration, non-controlled pH batch fermentations and without nutrients supplementation, 66 and 22% of lactose in the traditional cheese whey have been converted into lactobionic acid and lactic acid using Pseudomonas taetrolens and Lactobacillus casei, respectively. Those are important results that encourage to enhance the bioprocesses used in a cost-effective way in order to scale up an industrial production.

Lactobionic acid (LBA) is a bioactive compound that has become increasingly popular in medicine in recent years due to its unique properties. This chemical can be formed via the enzymatic oxidation of lactose using fungal oxidoreductive enzymes. This study aimed to intensify the synthesis of LBA using immobilised enzymes (cellobiose dehydrogenase from Phanerochaete chrysosporium (PchCDH) and laccase from Cerrena unicolor (CuLAC)) on chitosan microspheres. We used three different crosslinking agents: genipin, glutaraldehyde, and polyethyleneimine to activate the chitosan. The FTIR and CellDrop techniques were used to characterise the activated microspheres. Quantitative (HPLC) and qualitative (TLC) methods were used to determine the obtained LBA. The results show that the type of activator used influences the efficiency of the binding of the enzyme to the matrix. Furthermore, the amount of LBA formed depends on the type of system used. The use of a system in which one of the enzymes is immobilised on a PEI-activated carrier (PchCDH) and the other is free (CuLAC) proved to be the most optimal, as it yielded almost 100% conversion of lactose to lactobionic acid. Summarising the data obtained the following: lactobionic acid immobilised on chitosan microspheres has great potential for medical applications.

Lactobionic acid (LBA) has many potential applications. This study aimed to evaluate the application of LBA in ice cream production, including its effect on the physico‐chemical properties of ice cream mix, and overrun and melting behaviour of ice cream. The rheological properties of ice cream mix and ice cream made with LBA were evaluated. The physico‐chemical properties of ice cream produced with 2–3 g/kg LBA were comparable to ice cream made with a commercial stabiliser and emulsifier. However, the addition of LBA in higher concentration in the current study resulted in a harder ice cream texture and lower overrun. [ABSTRACT FROM AUTHOR]

Targeted-drug administration to liver reduces side effects by minimising drug distribution to non-target organs and increases therapeutic efficacy by boosting drug concentration in target cells. In this study, arabinogalactan-(AG), pullulan-(PL) and lactobionic acid-(LA) were selected as natural ligands to target asialoglycoprotein receptor-(ASGPR-1) present on hepatocytes. In silico docking studies were performed and binding affinities of novel ligands viz. palmitoylated AG-(PAG), lauroylated AG-(LAG), palmitoylated PL-(PPL), lauroylated PL-(LPL) and lactobionic acid–adipic acid dihydrazide conjugate-(LAD) were compared with AG, PL and LA. These novel ligands were successfully synthesized and characterized. The ligands were incorporated into drug loaded nanostructured lipid carriers-(NLCs) for surface functionalization. HepG2 cellular internalization of hepatocyte-targeted NLCs was studied using fluorescence microscopy and LAD-decorated-drug loaded NLCs giving maximum cellular uptake were studied using confocal microscopy. Toxicity potential of LAD-decorated NLCs was assessed in vivo. Molecular docking results suggested that among the ligands, order of binding affinity was found to be LAD>PAG > PPL > LPL > LAG. Acute toxicity studies revealed hemocompatibility and absence of organ toxicity for ligand LAD. Additionally, the results establish proof-of-concept of enhanced targeting efficacy of novel ASGPR targeting ligands. These ligands can be used for surface modification of nanocarriers for future targeted delivery in treating various liver disorders. [Display omitted] • Molecular docking studies of novel ligands with ASGPR target protein • Synthesis, characterization of ligands, design of ligand anchored drug loaded NLCs • In vitro HepG2 uptake and in vivo acute toxicity study in Swiss albino mice • LAD decorated drug loaded NLCs gave maximum HepG2 cellular uptake • Establishes proof of concept of enhanced efficacy of novel ASGPR targeting ligands [ABSTRACT FROM AUTHOR]

Acid whey causes a major disposal problem for the dairy industry due to its low pH and high salt concentration. Lactobionic acid (LBA) production by whey fermentation is an inexpensive process. The goal of this work was to employ acid whey for LBA production. Acid whey was fermented in a bioreactor, adding Pseudomonas taetrolens LMG 2336 at 30°C and 6.5 pH, with 1.5‐Lpm oxygen aeration and 350‐rpm agitation. Three fermentation tests were carried out with a different amount of inoculum (10%, 30% and 10% three times within 24 h). Results indicated that repeatedly adding P. taetrolens inoculum to the acid whey substrate allows a complete lactose conversion into LBA, while the lactose oxidation process was insufficient in the sample where the inoculum was only added at the beginning of the fermentation process (only 29.7% LBA production with 10% inoculum). The physiological heterogeneity of P. taetrolens was determined by multiparametric flow cytometry, and results showed that there was a phenotypic adaptation of the microorganism due to the changes observed in its heterogeneity and physiological state. The results achieved will help to recycle acid whey for value‐added product production such as LBA production. [ABSTRACT FROM AUTHOR]

Lactobionic acid (LBA) has recently emerged as an important substance in various industries, such as cosmetics, foods, and pharmaceuticals. In this study, we developed a simple, efficient, and high-throughput method for screening LBA-producing microorganisms. First, an agar plate was prepared to isolate LBA-producing microorganisms by utilizing the property of LBA to solubilize colloidal calcium carbonate (CaCO3), resulting in the formation of a clear halo around colonies on a nutrient broth agar plate containing CaCO3. Subsequently, LBA production from the isolated microorganisms was confirmed using high-performance liquid chromatography (HPLC). Approximately 560 colonies from soil samples in Ulsan, Korea were screened and a clear halo was observed around three colonies on the prepared LBA-screening agar plate. The culture supernatants of these three colonies were analyzed by HPLC and it was found that these strains could produce LBA from lactose. Phylogenetic analysis by comparing their 16S rRNA nucleotide sequences revealed that these strains were Pseudomonas spp. and Alcaligenes faecalis. This is the first report highlighting that A. faecalis can produce LBA. As per the aforementioned results, the LBA-screening method that we devised here is highly effective for isolating and identifying new LBA-producing microorganisms. [ABSTRACT FROM AUTHOR]

Enzymes produced by white rot fungi are involved in the synthesis of secondary metabolites with valuable biotechnological properties. One of these metabolites is lactobionic acid (LBA). The aim of this study was to characterize a novel enzyme system consisting of a cellobiose dehydrogenase from Phlebia lindtneri (PlCDH), a laccase from Cerrena unicolor (CuLAC), a redox mediator (ABTS or DCPIP), and lactose as a substrate. We used quantitative (HPLC) and qualitative methods (TLC, FTIR) to characterise the obtained LBA. The free radical scavenging effect of the synthesised LBA was assessed with the DPPH method. Bactericidal properties were tested against Gram-negative and Gram-positive bacteria. We obtained LBA in all the systems tested; however, the study showed that the temperature of 50 °C with the addition of ABTS was the most advantageous condition for the synthesis of lactobionic acid. A mixture with 13 mM LBA synthesised at 50 °C with DCPIP showed the best antioxidant properties (40% higher compared with the commercial reagent). Furthermore, LBA had an inhibitory effect on all the bacteria tested, but the effect was better against Gram-negative bacteria with growth inhibition no lower than 70%. Summarizing the obtained data, lactobionic acid derived in a multienzymatic system is a compound with great biotechnological potential.

[Display omitted] • Aqueous phase lactose (LA) oxidation was carried out in a monolithic stirrer reactor. • Experimental data were fitted using pseudo-homogeneous and heterogeneous models. • Rate-limiting step depends on the ratio of catalyst weight to initial LA moles: W / n L A 0 . • For low W / n L A 0 , the rate-limiting step is the surface chemical oxidation of LA. • For high W / n L A 0 , the rate-controlling step is the LA chemisorption over Au surface. The liquid-phase oxidation of lactose (LA) to lactobionic acid (LB) was studied over Au(2 %)/Al 2 O 3 nanostructured catalyst. Catalytic tests were carried out at 65 °C, varying O 2 partial pressures in the range of 0.21−1 bar and LA initial concentrations between 0.007 and 0.089 M. In all of the cases, the selectivity to LB was always 100 %. It was observed that the trends for the LA conversion (X LA) with time depends on the ratio of catalyst weight to initial LA moles W / n L A 0 and the initial LA concentration C L A 0 . Experimental data were interpreted by kinetic modelling applying pseudo-homogeneous and Langmuir-Hinshelwood-Hougen-Watson (LHHW) models. It was found that irreversible surface oxidation of LA rules the reaction rate when W / n L A 0 = 30 g mol−1. At the early stages, the reaction rates did not depend on the LA concentration, and thus the reaction order with respect to LA was zero. In this case, an LHHW model considering total coverage of the active sites gives a very good fitting of the experimental data. As LA was consumed, the progress of conversion with time is different for each case and the reaction order changes to positive. Now, a better fitting is obtained with an LHHW model in which partial coverage of the active sites is considered. When liquid phase was diluted in LA and W / n L A 0 = 95 g mol−1, the LA chemisorption becomes the controlling step. Therefore, the results obtained by kinetic modelling helped to explain the dependence of LA oxidation rate with C L A 0 and W / n L A 0 . [ABSTRACT FROM AUTHOR]

Synbiotic products are a type of functional food with great potential due to consumer interest in foods that improve health and/or reduce the risk of certain diseases. In this study, synbiotic macrocapsules were developed using Lactobacillus paracasei CBA L74 as probiotic and lactobionic acid (LBA) as prebiotic. Firstly, the probiotic was proven to be able to use LBA as the only substrate source checking their growth and lactic acid production. Then, four different types of capsules were produced using sodium alginate as matrix and different hardener solutions (CaCl2 and chitosan). The macrocapsules were characterised regarding their strength, and the best performing ones were used for further analysis. In order to obtain a synbiotic capsule characterized by a longer stability time due to low water activity, the capsules were dried using freeze and thermal drying. Successively, to revitalize the microorganisms, the capsules were rehydrated in two different media (saline solution and yogurt), subjected to simulated in vitro digestion tests and visually characterised. In addition, their viability over time was assessed. As a result, L. paracasei was able to grow using LBA as the only source of carbon with better production of lactic acid for prolonged periods. The more resistant freeze- and thermal-dried capsules showed differences in rehydration kinetics, and visual changes were also observed. In simulated in vitro digestion tests, capsules rehydrated in yogurt showed the best results in terms of survival. Regarding their viability over time, the importance of the use of chitosan was noted. [ABSTRACT FROM AUTHOR]

The aim of this paper was to assess the prebiotic properties of lactobionic acid in the human gastrointestinal model. Five different strains of probiotic, or potentially probiotic, bacteria were used in the microencapsulation process; these were Lactobacillus casei Shirota, Lactococcus lactis ATCC1, Lactobacillus fermentum, Bifidobacterium bifidum DSM 20456, and Bifidobacterium bifidum DSM 20082. Starch with a concentration of 4% (w/v) and a degree of substitution of 0.03 was used to produce the microcapsules. The alginian microcapsules we produced functioned as a protective barrier for the probiotic microorganisms closed in them, protecting them from adverse conditions in the human digestive tract. The microorganisms could thus survive the encapsulation process and the in vitro model digestion process while retaining the ability to produce biomass. Factors such as pH and time affect the solution of alginate microcapsules. The capsule solution began when a pH of 7.4 was reached; this corresponded to pH in the target probiotic site, an in vitro model of the colon. The capsules had completely dissolved after 24 h of digestion at a pH of 8. The addition of lactobionic acid stimulated the growth of probiotic and potentially probiotic bacteria, thus confirming its prebiotic properties. [ABSTRACT FROM AUTHOR]

The aim of this research was to develop a method of its production from whey using bacteria of the species Pseudomonas taetrolens. Analyses of the lactobionic acid production method from whey showed that the following factors have a significant effect on its efficiency: the frequency of whey batch feeding, pH and the type of bacteria application, i.e. microencapsulated vs. free. Lactose and lactobionic acid were assayed using high performance liquid chromatography (HPLC) and liquid chromatography-electrospray ionization-tandem mass spectrometry (LC–ESI–MS). The highest concentration of lactobionic acid of 22.03 mg/cm3 was obtained when whey was batch fed at 72-h intervals, pH was maintained at 6.25 and bacteria were enclosed in alginate microcapsules. [ABSTRACT FROM AUTHOR]

Lactobionic acid (LBA), a prebiotic with beneficial health properties, can be mixed with a probiotic, Lactobacillus plantarum CECT 9567, to prepare novel synbiotic coatings. Coatings deposited on cottage cheese contained either probiotic (PRO, L. plantarum CECT 9567), prebiotic (PRE2 and PRE4; 20 and 40 g L−1 of LBA, respectively) or synbiotic compositions (SYN2 and SYN4). Coated cottage cheeses were analysed to determine probiotic and LBA concentration changes during storage, their textural properties and investigate the survival of bacteria during simulated digestion. Before the digestion test, PRO, SYN2 and SYN4 met minimal requirements to attain probiotic category and PRE2, PRE4, SYN2 and SYN4 contained adequate quantities of LBA throughout the experiment. Textural properties of cheese samples varied, with changes in the stickiness parameter. The digestion test showed that only SYN2 and SYN4 maintained acceptable probiotic values after simulated digestion, due to the presence of LBA, which increased probiotic survival.

With high morbidity and death rates, liver cancer has become one of the most common cancers in the world. But, most chemotherapeutic anticancer drugs have high toxicity as well as low specificity. To improve the treatment modalities and enhance the therapeutic effect of liver cancer, a brand new liver-targeting nanoparticle (NP), Ent-11α-hydroxy-15-oxo-kaur-16-en-19-oic acid (5 F)-loaded cholic acid (CA)-functionalized star-shaped poly (lactic-co-glycolic acid) (PLGA)-polyethylene glycol (PEG)-lactobionic acid (LA) (5 F-loaded CA-PLGA-PEG-LA), was developed. The particle size, zeta potential, size distribution, surface morphology, drug loading content, drug encapsulation efficiency and drug release of 5 F-loaded NPs were characterized. Confocal microscopy and flow cytometry showed that the prepared NPs could be internalized by HepG2 cells. Furthermore, the cellular uptake efficiency of coumarin 6-loaded CA-PLGA-PEG-LA NPs was much better in compare with that of CA-PLGA-PEG and CA-PLGA NPs. Moreover, LA-conjugated NPs (CA-PLGA-PEG-LA NPs) enhanced fluorescence of HepG2 cells via ligand-mediated endocytosis. The antitumor effects of 5 F-loaded NPs were evaluated by the MTT assay in vitro and by a xenograft tumor model in vivo, demonstrating that targeted 5 F-loaded CA-PLGA-PEG-LA NPs were significantly superior to free 5 F and 5 F-loaded CA-PLGA-PEG NPs. All the results indicated the 5 F-loaded CA-PLGA-PEG-LA NPs can be employed as a novel potentially targeting drug delivery system for liver cancer therapy.

Production of lactobionic acid using an immobilized cellobiose dehydrogenase/laccase system on magnetic chitosan spheres • A new cellobiose dehydrogenase was identified from Aspergillus fumigatus. • Immobilized Af CDH showed better thermal stability than free enzyme. • Immobilized Af CDH/ Laccase system was efficient for oxidizing lactose into lactobionic acid. • Immobilized bi-enzyme system has good reusability retaining 70 % activity after 10 cycles. Lactobionic acid (LBA) has numerous promising applications in food, pharmaceutical, cosmetics and chemical fields. LBA can be produced by cellobiose dehydrogenase (CDH)/laccase (Lac) bi‐enzymatic system with redox mediator, in which CDH catalyzes the oxidation of lactose into LBA, while LAC serves as a regenerative enzyme to simultaneously regenerate the redox mediator as electron acceptor for CDH. Despite this CDH/LAC system is effective in catalyzing the oxidation of lactose into LBA, easy deactivation of free enzymes throughout the biocatalysis process limited its industrial implementation. In this study, a new cellobiose dehydrogenase from Aspergillus fumigatus (Af CDH) was characterized. Af CDH and LAC were separately immobilized on the glutaraldehyde-modified magnetic chitosan spheres (MCS) with the activity yields of immobilization 61.54 % and 14.1 %, respectively. Immobilized Af CDH displayed better thermal stability and retained 60 % of initial activity after incubation at 50 °C for 4 h, in contrast, the residual activity of free Af CDH was hardly detected under the same condition. Our study demonstrated that the immobilized Af CDH/LAC system was efficient for bioproduction of LBA. 100 g/L of lactose was completely converted to LBA with a space-time yield of 7.14 g/L h This immobilized Af CDH/LAC system had good reusability and retained 70 % activity after 10 cycles of reuse. [ABSTRACT FROM AUTHOR]

An in situ zeolite imidazole metal organic framework-90 (ZIF-90) modified capillary was prepared via the method of solvothermal synthesis. The coating of ZIF-90 was characterized by scanning electron microscopy, energy-dispersive X-ray spectrometry, and EOF. Capillary electrochromatography–based enantioseparation of the basic drugs propranolol (PRO), metoprolol (MET), atenolol (ATE), bisoprolol (BIS), and sotalol (SOT) was performed using lactobionic acid (LA) as the chiral selector. Compared with an uncoated silica capillary, the resolutions are greatly improved (PRO 1.40 → 3.23; MET 1.07 → 3.19; ATE 1.07 → 3.15; BIS 1.16 → 3.41; SOT 1.00 → 2.79). Effects of buffer pH values, proportion of organic additives, concentration of lactobionic acid, and applied voltage were investigated. [ABSTRACT FROM AUTHOR]

Lactobionic acid and sorbitol are produced from lactose and fructose in reactions catalyzed by glucose–fructose oxidoreductase and glucono-δ-lactonase, periplasmic enzymes present in Zymomonas mobilis cells. Considering the previously established laboratory-scale process parameters, the bioproduction of lactobionic acid was explored to enable the transfer of this technology to the productive sector. Aspects such as pH, temperature, reuse and storage conditions of Ca-alginate immobilized Z. mobilis cells, and large-scale bioconversion were assessed. Greatest catalyst performance was observed between pH range of 6.4 and 6.8 and from 39 to 43 °C. The immobilized biocatalyst was reused for twenty three 24-h batches preserving the enzymatic activity. The activity was maintained during biocatalyst storage for up to 120 days. Statistically similar results, approximately 510 mmol/L of lactobionic acid, were attained in bioconversion of 0.2 and 3.0 L, indicating the potential of this technique of lactobionic acid production to be scaled up to the industrial level. [ABSTRACT FROM AUTHOR]