Search Results (60)

The advancement of efficient drug delivery systems continues to pose a significant problem in pharmaceutical sciences, especially for compounds with limited water solubility. Lipid-based systems, including solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs), have emerged as viable options owing to their biocompatibility, capability to safeguard labile chemicals, and potential for prolonged release. Nonetheless, the encapsulation efficiency (EE) and release dynamics of these carriers can be enhanced by including cyclodextrins (CDs)—cyclic oligosaccharides recognized for their ability to form inclusion complexes with hydrophobic compounds. This article offers an extensive analysis of CD-modified SLNs and NLCs as multifunctional drug delivery systems. The article analyses the fundamental principles of these systems, highlighting the pre-complexation of the drug with cyclodextrins before lipid incorporation, co-encapsulation techniques, and surface adsorption after formulation. Attention is concentrated on the physicochemical interactions between cyclodextrins and lipid matrices, which influence essential factors such as particle size, encapsulation efficiency, and colloidal stability. The review includes characterization techniques, such as particle size analysis, zeta potential measurement, drug release studies, and Fourier-transform infrared spectroscopy (FT-IR)/Nuclear Magnetic Resonance (NMR) analyses. The study highlights the application of these systems across many routes of administration, including oral, topical, and mucosal, illustrating their adaptability and potential for targeted delivery. The review outlines current formulation challenges, including stability issues, drug leakage, and scalability concerns, and proposes solutions through advanced approaches, such as stimuli-responsive release mechanisms and computer modeling for system optimization. The study emphasizes the importance of regulatory aspects and outlines future directions in the development of CD-lipid hybrid nanocarriers, showcasing its potential to revolutionize the delivery of poorly soluble drugs. Full article

The production of novel oligosaccharides with potential prebiotic effects is of interest to expand the current market and explore the effectiveness of new functional carbohydrate forms. The utilization of glucansucrases is a cost-effective and environmentally friendly biotechnological strategy for producing novel gluco-oligosaccharides through acceptor reactions. In this study, an active glucansucrase (GS53) was used to produce gluco-oligosaccharides via its acceptor reactions with glucose, maltose, and maltotriose, and these oligosaccharides were tested in terms of structure and their gut microbiome modulatory effects. The formations of oligosaccharides were monitored by TLC analysis, and GS53 was active for the three acceptors but not for the other sugars tested. The structural characterization of the gluco-oligosaccharides by ¹H NMR analysis revealed the glycosylation of each acceptor with α-(1 → 3) and α-(1 → 6) linkages, whereas LC-MS analysis demonstrated the formations of DP 8, DP 7, and DP 6 oligosaccharides with acceptors maltose, maltotriose, and glucose, respectively. In vitro fecal fermentation analysis, in which microbial short-chain fatty acids (SCFAs) and microbial compositional changes were assessed using gas chromatography and 16S rRNA sequencing, respectively, demonstrated that the gluco-oligosaccharides formed SCFAs—particularly propionate and butyrate—at levels comparable to those observed with inulin, a well-established prebiotic. Additionally, the gluco-oligosaccharides were found to promote the growth of Bifidobacterium adolescentis and Blautia OTUs, which are known to have important physiological functions beneficial to human health. Overall, these results demonstrate that gluco-oligosaccharides synthesized using GS53 through acceptor reactions exhibit prebiotic potentials and could be utilized in the future as dietary supplements as well as in the development of functional foods targeting colonic health. Full article

The depolymerized products and oligosaccharide fractions from sea cucumber fucosylated glycosaminoglycans (FGs) are promising anticoagulant candidates, and more novel FG-derived oligosaccharides from low-priced sea cucumbers are expected to be obtained. This study isolated 5−12 oligomers (OF1−OF3) with unusual branches from β-eliminative depolymerized products of Colochirus quadrangularis FG (CqFG). Detailed NMR analyses showed that OF1−OF3 consisted of a chondroitin 4,6-sulfates backbone and some sulfated fucosyl branches (FucS), including monosaccharides (α-l-Fuc_2S4S, α-l-Fuc_3S, α-l-Fuc_4S, α-l-Fuc_2S3S4S, and α-l-Fuc_2S) and a disaccharide D-Gal_3S4S-α1,3-l-Fuc_2S4S with the ratio of ~36:35:10:7:3:9, attached to the C-3 position of β-d-GlcA or its derivatives, such as α-l-Δ4,5GlcA and β-d-GlcA-ol. Unusually, α-l-Fuc_3S was the main FucS branch; no α-l-Fuc_3S4S branch was found, and α-l-Fuc_2S3S4S and α-l-Fuc_2S branches were also found in OF1–OF3. The OF2 and OF3 could strongly inhibit the intrinsic and common coagulation pathways. Intrinsic FXase is a target of OF2 and OF3 inhibiting the intrinsic coagulation pathways, and the unusual side chains may increase the intrinsic FXase inhibitory activity. OF2 and OF3 showed negligible bleeding risk, and less bleeding than heparin (HP), low-molecular-weight heparins (LMWHs), and CqFG. These findings support novel FG oligosaccharides with some unusual branches from low-priced sea cucumbers to be prepared as safer anticoagulants. Full article

Background/Objectives: Dynamic changes in components from colostrum to mature milk occur in any mammal. However, the time it takes to reach the mature milk stage differs between taxa and species, as do the final concentrations of all the components. The white rhinoceros belongs to the family Perissodactyla, of which the milk and milk metabolome of the domesticated Equidae have been studied to some detail. Metabolomic information on the colostrum and milk of the Rhinocerotidae is lacking. Methods: Colostrum and milk were obtained from seven white rhinoceroses. Of note is that it was their first parturition and all followed the same diet, two factors known to affect colostrum composition and its changes during early lactation in domesticated mammals. Milk serum was prepared by the ultrafiltration of the milk samples. Untargeted ¹N NMR spectra were processed with Topspin 3.2, calibration was carried out according to the alanine signal and the identification of signals was carried out with Chenomx and assignments in the literature. Statistical analysis of the data was carried out using MetaboAnalyst 6.0. Results: The changes in the metabolites were followed during the first 7 days of lactation as well as on day 20. The amounts of amino acids and their derivatives, organic acids and lipid metabolites decreased over lactation, while carbohydrates and their derivatives increased. The colostrum phase ended on day 2, while the transition to mature milk seemed to be complete by day 7. From day 3 to 7, galactose metabolism and tyrosine metabolism were uprated. Of interest is the presence of the oligosaccharide 3′-sialyllactose on days 3 and 4 of lactation. Conclusions: Mainly the content of carbohydrates increased over lactation, specifically lactose. The 3′-sialyllactose content peaked on days 3 and 4 of lactation. The colostrum phase ended on day 2. The mature milk stage was reached by day 7. The galactose metabolism and tyrosine metabolism were uprated after day 3 of lactation. Full article

An alkali-soluble β-glucan (AHEP-A-b, 20 kDa) purified from Hericium erinaceus fruiting bodies, was structurally characterized and examined for antioxidant activity. Methylation analysis and NMR spectroscopy show that the backbone of AHEP-A-b is composed of (1→6)-linked-D-β-glucopyran residues, branched at O-3 of glucopyranose (Glcp) residues with [→3)-β-D-Glcp-(1→] oligosaccharides or single unit of β-Glcp. Periodate oxidation analysis and matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS) indicate that the degree of polymerization (DP) of [→3)-β-D-Glcp-(1→] side chains is 2 to 8. Functionally, AHEP-A-b is a relatively strong antioxidant as demonstrated by using 2, 2′-azino-bis-(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) free radical (ABTS^·+), 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals, and hydroxyl radicals scavenging assays. The present study lays the foundation for further studies into structure-activity relationships of polysaccharides from H. erinaceus. Full article

The yellow pea (Pisum sativum L. ‘Eso’, sin. Lathyrus oleracaeus Lam.(YP)) is an annual herbaceous plant that belongs to the Fabaceae family. Peas, along with other legumes, are an excellent source of proteins and essential amino acids; the yellow variety is known for maintaining a good protein profile even if subjected to industrial processing. However, the presence of antinutrients, such as phytates and oligosaccharides, limits its consumption as a fresh legume to its use as a source of isolated proteins or for animal feed. The aim of the study is to evaluate the changes in the entire phytochemical profile of YP seeds as a function of the harvest time. YPs harvested at about 40, 50, 60, and 70 days from sowing were examined by high-resolution NMR spectroscopy employing ¹H-NMR, ¹H-¹H TOCSY, and ¹H-¹³C HSQC. In total, 40 molecular species were identified and quantified; it was observed that there was a monotonous decrease in amino acids, carbohydrates, and secondary metabolites as a function of time. Antinutrient levels increased, but only in later sampling times. This study identified the optimal harvest time for yellow peas “Eso” in the fortieth day from sowing, adding new information about the best nutritional outcome for humans. Full article

Mulberry leaves contain α-glucosidase inhibitors, which have hypoglycemic effects and are considered functional foods. However, few reports have covered the effects of mulberry leaf components on normal gut microbiota and gut metabolites. Herein, gut microbiota analysis and NMR-based metabolomics were performed on the feces of mulberry leaf powder (MLP)-treated mice to determine the effects of long-term MLP consumption. Gut microbiota in the mouse were analyzed using 16S-rRNA gene sequencing, and no significant differences were revealed in the diversity and community structure of the gut microbiota in the C57BL/6 mice with or without MLP supplementation. Thirty-nine metabolites were identified via ¹H-NMR analysis, and carbohydrates and amino acids were significantly (p < 0.01–0.05) altered upon MLP treatment. In the MLP-treated group, there was a marked increase and decrease in maltose and glucose concentrations, respectively, possibly due to the degradation inhibitory activity of oligosaccharides. After 5 weeks, all amino acid concentrations decreased. Furthermore, despite clear fluctuations in fecal saccharide concentrations, short-chain fatty acid production via intestinal bacterial metabolism was not strongly affected. This study provides the knowledge that MLP administration can alter the gut metabolites without affecting the normal gut microbiota, which is useful for considering MLP as a healthy food source. Full article

The Edwardsiella genus presents five different pathogenic species: Edwardsiella tarda, E. anguillarum, E. piscicida, E. hoshinae and E. ictaluri. These species cause infections mainly in fish, but they can also infect reptiles, birds or humans. Lipopolysaccharide (endotoxin) plays an important role in the pathogenesis of these bacteria. For the first time, the chemical structure and genomics of the lipopolysaccharide (LPS) core oligosaccharides of E. piscicida, E. anguillarum, E. hoshinae and E. ictaluri were studied. The complete gene assignments for all core biosynthesis gene functions were acquired. The structure of core oligosaccharides was investigated by ¹H and ¹³C nuclear magnetic resonance (NMR) spectroscopy. The structures of E. piscicida and E. anguillarum core oligosaccharides show the presence of →3,4)-L-glycero-α-D-manno-Hepp, two terminal β-D-Glcp, →2,3,7)-L-glycero-α-D-manno-Hepp, →7)-L-glycero-α-D-manno-Hepp, terminal α-D-GlcpN, two →4)-α-D-GalpA, → 3)-α-D-GlcpNAc, terminal β-D-Galp and →5-substituted Kdo. E. hoshinare core oligosaccharide shows only one terminal β-D-Glcp, and instead of terminal β-D-Galp a terminal α-D-GlcpNAc. E. ictaluri core oligosaccharide shows only one terminal β-D-Glcp, one →4)-α-D-GalpA and do not have terminal α-D-GlcpN (see complementary figure). Full article

Cyclodextrins, cyclic oligosaccharides composed of five or more α-D-glucopyranoside units linked by α-1,4 glycosidic bonds, are widely used both in their native forms as well as the components of more sophisticated materials. Over the last 30 years, solid-state nuclear magnetic resonance (ssNMR) has been used to characterize cyclodextrins (CDs) and CD-including systems, such as host–guest complexes or even more sophisticated macromolecules. In this review, the examples of such studies have been gathered and discussed. Due to the variety of possible ssNMR experiments, the most common approaches have been presented to provide the overview of the strategies employed to characterize those useful materials. Full article

Low-molecular-weight carrageenan has attracted great interest because it shows advantages in solubility, absorption efficiency, and bioavailability compared to original carrageenan. However more environment-friendly and efficient methods to prepare low-molecular-weight carrageenan are still in great need. In the present study, a photocatalytic degradation method with only TiO₂ has been developed and it could decrease the average molecular weight of κ-carrageenan to 4 kDa within 6 h. The comparison of the chemical compositions of the degradation products with those of carrageenan by FT-IR, NMR, etc., indicates no obvious removement of sulfate group, which is essential for bioactivities. Then 20 carrageenan oligosaccharides in the degradation products were identified by HPLC-MSⁿ, and 75% of them possessed AnGal or its decarbonylated derivative at their reducing end, indicating that photocatalysis is preferential to break the glycosidic bond of AnGal. Moreover, the analysis results rheology and Cryo-SEM demonstrated that the gel property decreased gradually. Therefore, the present study demonstrated that the photocatalytic method with TiO₂ as the only catalyst has the potential to prepare low-molecular-weight carrageenan with high sulfation degree and low viscosity, and it also proposed the degradation rules after characterizing the degradation products. Thus, the present study provides an effective green method for the degradation of carrageenan. Full article

Due to the environmental problems generated by petroleum derivative polymers as mentioned in Agenda 2030, the use of natural polymers is increasing. Among them, cellulose and chitin are the most widespread biopolymers available in nature. Chitosan, obtained from chitin, is a really good candidate to develop nanocarriers due to its polyelectrolyte nature and ease of chemical modification. However, chitosan presents a solubility drawback in an aqueous medium at physiological pH (pH = 7.4), which restricts its applicability in biomedicine. In this work, nanogels were successfully synthesized from chitosan systems with different water solubilities (chitosan, oligosaccharide chitosan, and quaternized chitosan) using the reverse microemulsion method and polyethylene glycol diacid (PEGBCOOH) as a covalent cross-linking agent. Cross-linking with PEGBCOOH was analyzed by proton nuclear magnetic resonance (¹H-NMR), which allowed for nanogels to be prepared whose size and swelling were comparatively studied by transmission electron microscopy (TEM) and dynamic light scattering (DLS) and zeta potential, respectively. The particle size of the swollen nanogels showed a different pH-responsive behavior that decreased for chitosan, increased for oligosaccharide chitosan, and remained constant for quaternized chitosan. Nevertheless, a drastic reduction was observed in all cases in the culture medium. Along the same line, the dispersibility of the synthesized nanogels in different media was comparatively evaluated, showing similar values for the nanogels prepared from soluble chitosans than for water insoluble chitosan as a consequence of the cross-linking with PEGBCOOH. After 6 months of storage of the dried nanogels, the water dispersibility values remained constant in all cases, demonstrating the stabilizing effect of the employed cross-linking agent and the potential use of synthesized nanogels as substrates for drug delivery. Full article

The molecular weight, the triple-helix conformation, the monosaccharide content, the manner of glycosidic linkages, and the polysaccharide conjugates of polysaccharides all affect bioactivity. The purpose of this study was to determine how different molecular weights affected the bioactivity of the Lycium barbarum polysaccharides (LBPs). By ethanol-graded precipitation and ultrafiltration membrane separation, one oligosaccharide (LBPs-1, 1.912 kDa) and two polysaccharides (LBPs-2, 7.481 kDa; LBPs-3, 46.239 kDa) were obtained from Lycium barbarum. While the major component of LBPs-1 and LBPs-2 was glucose, the main constituents of LBPs-3 were arabinose, galactose, and glucose. LBPs-2 and LBPs-3 exhibited triple-helix conformations, as evidenced by the Congo red experiment and AFM data. Sugar residues of LBPs-2 and LBPs-3 were elucidated by NMR spectra. The polysaccharides (LBPs-2 and LBPs-3) exhibited much higher antioxidant capacities than oligosaccharide (LBPs-1). LBPs-3 showed higher oxygen radical absorbance capacity (ORAC) and superoxide dismutase (SOD) activity than LBPs-2, but a lower capability for scavenging ABTS⁺ radicals. In zebrafish, LBPs-2 and LBPs-3 boosted the growth of T-lymphocytes and macrophages, enhanced the immunological response, and mitigated the immune damage generated by VTI. In addition to the molecular weight, the results indicated that the biological activities would be the consequence of various aspects, such as the monosaccharide composition ratio, the chemical composition, and the chemical reaction mechanism. Full article

Oxidative stress initiated by reactive oxygen species (ROS) is the cause of many acquired or congenital skin diseases. Oral antioxidants or using topical antioxidants preparations may bring the nonspecific distribution of drugs or anaphylaxis due to repeated use. In this study, a biocompatible gene vector by cross-linking of chitosan-oligosaccharide (CSO) and N,N’-cystamine-bis-acrylamide (CBA) was synthesized (CSO-CBA), which could carry therapeutic genes into the skin, express functional proteins in epidermal cells, and play an efficient antioxidant effect. Infrared and ¹H NMR spectrum data showed that CSO-CBA was successfully synthesized. Gel electrophoresis results showed that the gene could be successfully compressed by the carrier and can be released in a reducing environment. Hemolysis experiments showed that the carrier had good biocompatibility. Transdermal gene delivery experiments proved that the vector can bring genes into the skin, express functional proteins, and protect the skin from reactive oxygen species damage after 7 days of administration. Skin compatibility experiments show that our therapy is biocompatible. Our study provides a minimally invasive and painless, high-biocompatibility, and long-term effective treatment for skin damage caused by reactive oxygen species, which has a potential application. Full article

The aim of this study is to synthesize phenethyl-conjugated chitosan oligosaccharide (COS) (abbreviated as ChitoPEITC) conjugates and then fabricate chlorin E6 (Ce6)-incorporated nanophotosensitizers for photodynamic therapy (PDT) of HCT-116 colon carcinoma cells. PEITC was conjugated with the amine group of COS. Ce6-incorporated nanophotosensitizers using ChitoPEITC (ChitoPEITC nanophotosensitizers) were fabricated by dialysis method. ¹H nuclear magnetic resonance (NMR) spectra showed that specific peaks of COS and PEITC were observed at ChitoPEITC conjugates. Transmission electron microscope (TEM) confirmed that ChitoPEITC nanophotosensitizers have spherical shapes with small hydrodynamic diameters less than 200 nm. The higher PEITC contents in the ChitoPEITC copolymer resulted in a slower release rate of Ce6 from nanophotosensitizers. Furthermore, the higher Ce6 contents resulted in a slower release rate of Ce6. In cell culture study, ChitoPEITC nanophotosensitizers showed low toxicity against normal CCD986Sk human skin fibroblast cells and HCT-116 human colon carcinoma cells in the absence of light irradiation. ChitoPEITC nanophotosensitizers showed a significantly higher Ce6 uptake ratio than that of free Ce6. Under light irradiation, cellular reactive oxygen species (ROS) production of nanophotosensitizers was significantly higher than that of free Ce6. Especially, PEITC and/or ChitoPEITC themselves contributed to the production of cellular ROS regardless of light irradiation. ChitoPEITC nanophotosensitizers showed significantly higher PDT efficacy against HCT-116 cells than that of free Ce6. These results indicate that ChitoPEITC nanophotosensitizers have superior potential in Ce6 uptake, ROS production and PDT efficacy. In the HCT-116 cell-bearing mice tumor-xenograft model, ChitoPEITC nanophotosensitizers efficiently inhibited growth of tumor volume rather than free Ce6. In the animal imaging study, ChitoPEITC nanophotosensitizers were concentrated in the tumor tissue, i.e., fluorescence intensity in the tumor tissue was stronger than that of other tissues. We suggest that ChitoPEITC nanophotosensitizers are a promising candidate for the treatment of human colon cancer cells. Full article