Fucoidan Nanoparticles Research Articles

Design and preparation of NMN nanoparticles based on protein-marine polysaccharide with increased NAD+ level in D-galactose induced aging mice model

Nicotinamide mononucleotide (NMN) is being investigated for its ability to address the decline in NAD+ level during aging. This study aimed to construct a delivery system based on ovalbumin and fucoidan nanoparticles to ameliorate the bioaccessibility of NMN by increasing NAD+ level in aging mouse model. The NMN-loaded ovalbumin and fucoidan nanoparticles (OFNPs) were about 177 nm formed by the interplay of hydrogen bonds between ovalbumin and fucoidan. Compared with free NMN, NMN-loaded OFNPs intervention could obviously improve the antioxidant enzyme activity of senescent cell induced by D-galactose. The NMN-loaded OFNPs treatment could ameliorate the loss of weight and organ index induced by senescence, and maintain the water content for the aging mice. The Morris maze test indicated that hitting blind side frequency and escape time of NMN-loaded OFNPs group decreased by 13% and 35% compared with that of free NMN group. Furthermore, the NMN-loaded OFNPs significantly alleviated the age-related oxidative stress and increased the generation of NAD+ 1.34 times by improving the bioaccessibility of NMN. Our data in this study supplied a strategy to enhance the bioavailability of NMN in senescence treatment.

Layer-by-layer coating of Lacticaseibacillus rhamnosus GG (LGG) using chitosan and zein/tween-80/fucoidan nanoparticles to enhance LGG's survival under adverse conditions

Lacticaseibacillus rhamnosus GG (LGG) is a widely recognized probiotic known for its health-promoting properties, such as supporting digestive and oral health, bolstering immune function, aiding in weight management, and potentially enhancing psychological well-being. However, unlocking its full potential necessitates addressing challenges like extending its shelf life and fortifying its resilience against harsh acidic conditions in the gastrointestinal tract. In this study, we employed a layer-by-layer (LbL) technique, using oppositely charged polymers — chitosan (CHI) and zein/tween-80/fucoidan nanoparticles (ZTFD), to encapsulate LGG, aiming to enhance LGG's functional attributes and viability. Our hypothesis centered on LbL encapsulation's potential to bolster LGG's survival and stability in adverse conditions by creating robust protective layers via electrostatic interactions between chitosan and ZTFD nanoparticles. Results demonstrated that (CHI/ZTFD)2-LGG, the two bi-layer coated variant, exhibited superior survival rates under extreme conditions such as freezing, heat, and storage, outperforming uncoated LGG. Moreover, in simulated gastrointestinal fluid over 120 min, plain LGG suffered a 3.92 log CFU/mL reduction, while (CHI/ZTFD)2-LGG experienced a milder 2.15 log CFU/mL reduction. In an in vivo mice study, (CHI/ZTFD)2-LGG displayed a remarkable 63.7-fold increase in survival compared to plain LGG. These findings highlight the potential of LbL encapsulation in enhancing LGG's robustness, enabling its use as a probiotic in food and pharmaceutical applications. The incorporation of encapsulated LGG into formulations holds promise for advancing probiotic utilization and enhancing consumer health.

Tridax procumbens–mediated one pot synthesis of silver-doped fucoidan nanoparticles and their antibacterial, antioxidant, and anti-inflammatory efficacy

Tridax procumbens–mediated one pot synthesis of silver-doped fucoidan nanoparticles and their antibacterial, antioxidant, and anti-inflammatory efficacy

Development of polyethyleneimine cross-linked fucoidan nanoparticles as delivery systems for improved anticancer efficiency of cytarabine in breast adenocarcinoma cell lines

Schematic Representation of Synthesis and Delivery of Cytarabine loaded Fucoidan nanoparticles (CFNP).

Molecular Mechanism of Fucoidan Nanoparticles as Protector on Endothelial Cell Dysfunction in Diabetic Rats' Aortas.

Antioxidants have an important role in protecting against diabetes complications such as vascular endothelial cell damage. Fucoidan has strong antioxidant properties, therefore the aim of this study was to investigate the protective mechanism of fucoidan nanoparticles through the pathway of antioxidant activity against streptozotocin-induced diabetic aortic endothelial cell dysfunction in rats. Fucoidan nanoparticles are made utilizing high-energy ball milling. This research consists of five groups, namely: control rats, rats were administered aquadest; diabetic rats, rats were administered streptozotocin (STZ); fucoidan nanoparticle rats, rats were administered STZ and fucoidan nanoparticles. Aortic tissue was collected for the evaluation of ROS (reactive oxygen species), Malondialdehyde (MDA), superoxide Dismutase (SOD), Glutathione Peroxidase (GPx), Nuclear factor erythroid-2-related factor 2 (Nrf2), Nitric Oxide (NO), cyclic Guanosine Monophosphate (cGMP), relaxation response of acetylcholine (Ach), and the diameter of the aorta. The size distribution of the fucoidan nanoparticles was 267.2 ± 42.8 nm. Administration of fucoidan nanoparticles decreased the levels of ROS and MDA, and increased the levels of SOD, levels of GPx, Nrf2 expression, NO levels, cGMP expression, the relaxation response of Ach, and lumen diameter of the aorta, which are significantly different when compared with diabetic rats, p < 0.05. In this study, we concluded that the mechanism pathway of fucoidan nanoparticles prevents aortic endothelial cell dysfunction in diabetic rats through antioxidant activity by reducing ROS and MDA and incrementing SOD levels, GPx levels, and Nrf2 expression. All of these can lead to an elevated relaxation response effect of Ach and an increase in the lumen diameter of the aorta, which indicates a protective effect of fucoidan nanoparticles on aortic endothelial cells.

Synthesis and Characterization of Fucoidan-Chitosan Nanoparticles Targeting P-Selectin for Effective Atherosclerosis Therapy.

Atherosclerosis is the key pathogenesis of cardiovascular diseases; oxidative stress, which is induced by the generated excess reactive oxygen species (ROS), has been a crucial mechanism underlying this pathology. Nanoparticles (NPs) represent a novel strategy for the development of potential therapies against atherosclerosis, and multifunctional NPs possessing antioxidative capacities hold promise for amelioration of vascular injury caused by ROS and for evading off-target effects; materials that are currently used for NP synthesis often serve as vehicles that do not possess intrinsic biological activities; however, they may affect the surrounding healthy environment due to decomposition of products. Herein, we used nontoxic fucoidan, a sulfated polysaccharide derived from a marine organism, to develop chitosan–fucoidan nanoparticles (CFNs). Then, by binding to P-selectin, an inflammatory adhesion exhibited molecule expression on the endothelial cells and activated platelets, blocking leukocyte recruitment and rolling on platelets and endothelium. CFNs exhibit antioxidant and anti-inflammatory properties. Nevertheless, by now, the application of CFNs for the target delivery regarding therapeutics specific to atherosclerotic plaques is not well investigated. The produced CFNs were physicochemically characterized using transmission electron microscopy (TEM), together with Fourier transform infrared spectroscopy (FTIR). Evaluations of the in vitro antioxidant as well as anti-inflammatory activities exhibited by CFNs were based on the measurement of their ROS scavenging abilities and investigating inflammatory mediator levels. The in vivo pharmacokinetics and binding efficiency of the CFNs to atherosclerotic plaques were also evaluated. The therapeutic effects indicated that CFNs effectively suppressed local oxidative stress and inflammation by targeting P-selectin in atheromatous plaques and thereby preventing the progression of atherosclerosis.

CHARACTERIZATION OF NANOPARTICLES CONDITIONED MEDIUM ADIPOSE TISSUE MESENCHYMAL STEM CELL (CM-ATMSC)

Objective: The aims of this study were to formulate and characterize the nanoparticles containing conditioned medium adipose tissue&#x0D; mesenchymal stem cell (CM-ATMSC).&#x0D; Methods: Adipose Tissue Mesenchymal Stem Cell (AT-MSC) was cultured with supplemented Modified Eagle Medium (MEM) Alpha in an incubator with 37 °C and 5% CO2. The conditioned medium was collected when the cells were confluent. Nanoparticles were characterized in the term of morphology using transmission electron microscopy (TEM), particle size, zeta potential, loading capacity, entrapment efficiency, and drug release.&#x0D; Results: CM-ATMSC nanoparticles had the smallest particle size, namely chitosan-inulin nanoparticles with particle size of 128 nm, and the largest particle was modified chitosan (thiomer)-fucoidan nanoparticles with particle size of 254.3 nm. Based on zeta potential results, it is known that the resulting nanoparticle suspension was stable.&#x0D; Conclusion: The resulting nanoparticle suspension was stable and the smallest CM-ATMSC nanoparticle demonstrated the particle size of 128 nm. The results showed that the nanoparticles of CM-ATMSC have been successfully prepared.

Antioxidative Stress and Anti-Inflammatory Activity of Fucoidan Nanoparticles against Nephropathy of Streptozotocin-Induced Diabetes in Rats.

Oxidative stress and inflammation have been shown to interact and have the role of importance in causing diabetic nephropathy complications. Fucoidan has a strong antioxidant and anti-inflammation effect, so the aim of this research was to evaluate the antioxidative stress and anti-inflammatory effect of fucoidan nanoparticles against nephropathy of streptozotocin-induced diabetes in rats. Fucoidan nanoparticles are characterized using dynamic light scattering (DLS) and scanning electron microscope (SEM). The rats were randomized into the control group (were given with aquadest), streptozotocin group (were injected with streptozotocin at a dose of 55 mg/kg BW i.p.), and fucoidan nanoparticle group (were given orally with fucoidan at doses 75, 150, and 300 mg/kg BW and then injected streptozotocin at a dose of 55 mg/kg BW i.p.). The blood was taken to evaluate the level of blood urea nitrogen (BUN) and creatinine. The kidney tissues were collected to measure malondialdehyde (MDA), interleukin-6 (IL-6), and tumor necrosis factor α (TNF-α) by ELISA; superoxide dismutase (SOD), and glutathione peroxidase (GPx) by immunohistochemical staining and histological observation by Hematoxylin & Eosin (H&E) staining. The DLS demonstrated that the fucoidan nanoparticle size was 330.6 ± 58.8 nm, and the SEM showed an irregular shape with a rough surface image. The administration of streptozotocin significantly increased BUN, creatinine, MDA, IL-6, and TNF-α levels, whereas expression of SOD and GPx decreased as compared with the control group (p < 0.05). The administration of fucoidan nanoparticles only at a dose of 300 mg/kg BW significantly decreases BUN, creatinine, MDA, IL-6, and TNF-α levels. However, fucoidan nanoparticles at a dose of 300 mg/kg BW significantly increase SOD and GPx expression as compared with the streptozotocin group (p < 0.05). The administration of streptozotocin caused the loss of normal kidney cell structure and necrosis, while treatment with fucoidan nanoparticles improved renal cell necrosis. It can be concluded that fucoidan nanoparticles are promising agents in terms of the protection afforded against streptozotocin-induced nephropathy through antioxidative stress by decreasing MDA and increasing SOD and GPx and through anti-inflammatory effect by decreasing levels of IL-6 and TNF-α.

Fucoidan-Based Nanoparticles with Inherently Therapeutic Efficacy for Cancer Treatment.

The anticancer properties of fucoidan have been widely studied in cancer research. However, the lack of safety information on the parenteral administration of fucoidan and its rapid clearance from the system have limited its application. Herein, we assessed the therapeutic efficacy and safety of fucoidan and developed fucoidan nanoparticles (FuNPs) to enhance their therapeutic effect in the mouse model of breast cancer. FuNPs were synthesized through the emulsion method, and the stable colloid has an average size of 216.3 nm. FuNPs were efficiently internalized into breast cancer cells in vitro, demonstrating an enhanced antitumor activity in comparison with free form fucoidan. After the treatment of FuNPs, the tumor progression was significantly inhibited in viv. The tumor volume was reduced by 2.49-fold compared with the control group. Moreover, the inhibition of the invasion of tumor cells into the lungs revealed the antimetastatic properties of the FuNPs. FuNPs, as naturally marine polysaccharide-based nanoparticles, have shown their broader therapeutic window and enhanced antimetastatic ability, opening an avenue to the development of the inherently therapeutic nanomedicines.

Undaria pinnatifida fucoidan nanoparticles loaded with quinacrine attenuate growth and metastasis of pancreatic cancer

Pancreatic cancer is a devastating gastrointestinal tumor with limited Chemotherapeutic options. Treatment is restricted by its poor vascularity and dense surrounding stroma. Quinacrine is a repositioned drug with an anticancer activity but suffers a limited ability to reach tumor cells. This could be enhanced using nanotechnology by the preparation of quinacrine-loaded Undaria pinnatifida fucoidan nanoparticles. The system exploited fucoidan as both a delivery system of natural origin and active targeting ligand. Lactoferrin was added as a second active targeting ligand. Single and dual-targeted particles prepared through nanoprecipitation and ionic interaction respectively were appraised. Both particles showed a size lower than 200 nm, entrapment efficiency of 80% and a pH-dependent release of the drug in the acidic environment of the tumor. The anticancer activity of quinacrine was enhanced by 5.7 folds in dual targeted particles compared to drug solution with a higher ability to inhibit migration and invasion of cancer. In vivo, these particles showed a 68% reduction in tumor volume compared to only 20% for drug solution. In addition, they showed a higher animals' survival rate with no hepatotoxicity. Hence, these particles could be an effective option for the eradication of pancreatic cancer cells.

Development and characterization of soybean protein isolate and fucoidan nanoparticles for curcumin encapsulation

Curcumin (Cur) is a natural polyphenol with beneficial biological and pharmacological activities; however, it has limited applications owing to its low solubility and light sensitivity. The protein-polysaccharide complex can effectively embed lipid-soluble drugs to increase their stability and dispensability in aqueous solutions. Soybean protein isolate (Spi) and fucoidan (Fuc) were used as a polymer matrix, and core-shell nanoparticles were prepared to encapsulate Cur via electrostatic interaction under acidic and neutral conditions. The structure of the Spi-Fuc nanoparticles was studied via Fourier-transform infrared spectroscopy, transmission electron microscopy, and scanning electron microscopy. Concurrently, we evaluated the efficacy of the nanoparticles based on stability, drug loading rate, and simulated release. Our results showed that the Spi-Fuc nanoparticles (size, approximately 236.56 nm) had a spherical, core-shell structure and that they could effectively load Cur with an embedding efficiency of >95%; moreover, the system had long-term dispersion stability. Thus, we provide a simple method for Cur delivery, which can also be potentially used for delivering lipid-soluble active ingredients.

Selective Anticancer Therapy Using Pro-Oxidant Drug-Loaded Chitosan-Fucoidan Nanoparticles.

Pro-oxidant therapy exploiting pro-oxidant drugs that can trigger cytotoxic oxidative stress in cancer cells has emerged as an innovative strategy for cancer-specific therapy. Piperlongumine (PL) has gained great interest as a novel pro-oxidant agent, because it has an ability to trigger cancer-specific apoptosis through the increase of oxidative stress in cancer cells. However, the use of PL is limited in the clinic because of its hydrophobic nature. In this study, chitosan- and fucoidan-based nanoparticles were prepared for the effective intracellular delivery of PL into cancer cells. Chitosan and fucoidan formed nanoparticles by ionic gelation. The chitosan- and fucoidan-based nanoparticles (CS–F NPs) effectively encapsulated PL, and increased its water solubility and bioavailability. CS–F NPs showed very low cytotoxicity in human prostate cancer cells, demonstrating its high potential for in vivo applications. The PL-loaded chitosan–fucoidan nanoparticles (PL-CS–F NPs) efficiently killed human prostate cancer cells via PL-induced intracellular reactive oxygen species (ROS) generation. This study demonstrates that CS–F NPs are promising natural polymer-based drug carriers for safe and effective PL delivery.

Improved chemotherapy against breast cancer through immunotherapeutic activity of fucoidan decorated electrostatically assembled nanoparticles bearing doxorubicin

Immunotherapeutic nanoparticles (NPs) could be a viable option for delivering cytotoxic agents in a manner which suppresses their toxic manifestations. Doxorubicin (DOX) loaded NPs were prepared using fucoidan (FCD), an immunomodulatory polysaccharide and evaluated against cancer. FCD was electrostatically assembled with cationic polyethylenimine (PEI) through intermolecular electrostatic interactions to develop an immunomodulatory platform to deliver DOX. FCD NPs offered improved cytotoxicity (2.64 folds), cell cycle arrest in G1-S phase (34.65%) and apoptosis (66.12%) in tumor cells compared to free DOX. The enhanced apoptosis was due to raised mitochondrial depolarization (88.00%). In vivo anticancer activity in 4T1 induced tumor bearing BALB/c mice demonstrated a 2.95 folds enhanced efficacy of NPs. Importantly, NPs treatment generated an immunotherapeutic response indicated by gradual increment of the plasma IL-12 levels and reversed polarization of tumor associated macrophages (TAMs) towards M1 subtype. Furthermore, pharmacokinetic study suggested that NPs administration in tumor infested mice caused serum DOX levels to vary in a biphasic pattern, with twin peaks occurring at 1 h and 6 h which help in maintaining preferential drug localization in tumor. Developed NPs would be an excellent approach for improved immune-chemotherapy (in terms of efficacy, safety and immunocompetency) against cancer.

Investigation of Fucoidan-Oleic Acid Conjugate for Delivery of Curcumin and Paclitaxel.

Nanoparticles for a specific delivery are likely to be designed for cancer therapeutic effectiveness and improvement. In this study, a fucoidan-oleic acid conjugate was prepared and investigated in terms of loading capacity for poorly water-soluble anti-cancer drugs to maximize effectiveness of the treatment. Fucoidan was used as a hydrophilic portion of an amphiphilic structure for improving cancer therapeutic effects. Paclitaxel and curcumin were chosen as other model drugs loaded in the conjugates. The results showed that self-assembled nanoparticles with different sizes and morphologies could be prepared with two different concentrations of oleic acid as hydrophobic portion. Moreover, loading efficiency and release patterns of these drugs were mainly dependent on the hydrophobic interaction between drugs and oleic acid. It was also revealed that fucoidan and curcumin were released higher at pH 4.5 than at the physiological condition (pH 7.4), thus, facilitating the delivery and maximizing effects of the anticancer agents on cancer cells. On the contrary, paclitaxel from fucoidan nanoparticles was released faster at pH 7.4. The exploration of fucoidan-oleic acid conjugate could be considered as promising nanomedicines for cancer therapeutics.

Cytotoxic Effects of Fucoidan Nanoparticles against Osteosarcoma

In this study, we analyzed the size-dependent bioactivities of fucoidan by comparing the cytotoxic effects of native fucoidan and fucoidan lipid nanoparticles on osteosarcoma in vitro and in vivo. In vitro experiments indicated that nanoparticle fucoidan induced apoptosis of an osteosarcoma cell line more efficiently than native fucoidan. The more potent effects of nanoparticle fucoidan, relative to native fucoidan, were confirmed in vivo using a xenograft osteosarcoma model. Caco-2 cell transport studies showed that permeation of nanoparticle fucoidan was higher than native fucoidan. The higher bioactivity and superior bioavailability of nanoparticle fucoidan could potentially be utilized to develop novel therapies for osteosarcoma.

Preparation and characterization of polysaccharide-based nanoparticles with anticoagulant activity

The aim of this study was to produce and characterize nanoparticles (NPs), combining chondroitin sulfate (CS) and fucoidan (FC) with chitosan for therapeutic purposes. These NPs were characterized by dynamic light scattering, zeta potential determination, and transmission electronic microscopy. The anticoagulant activity was determined for FC NPs and compared with FC solution at the same concentration. FC NPs showed regular shapes and better anticoagulant activity than free polysaccharide solution. FC solution did not affect coagulation compared to FC NPs, which increased up to two-fold, even at a lower concentration. Cytotoxicity and permeability tests were conducted using Caco-2 cell monolayer, exhibiting no toxic effect in this cell line and higher permeability for NP2 samples than FC solution at the same concentration.

免疫賦活成分含有キトサンナノ粒子の調製と評価

In this work, chitosan-based nanoparticles were applied to enhance efficacy of the immunostimulating agents. Lactoferrin (LF) and fucoidan (FUC) were chosen as immunostimulating agents. As to LF, chitosan/alginate/calcium complex microparticles were prepared as its drug carrier. The microparticles had a size of 1 – 2 μm, and showed relatively high LF content. The LF content and release rate were depended on the concentration of the chitosan solution used for the treatment of microparticles. Efficacy was investigated by the pre-treatment with oral administration to rats with carrageenan-induced edema. The microparticles exhibited better efficacy than LF solution. In addition, chitosan-based nanoparticles containing FUC were prepared and evaluated on the usefulness. From the particle characteristics, N-trimethylchitosan(TMC)/FUC nanoparticles were considered to be possibly useful nanoparticles, rather than chitosan/FUC nanoparticles. TMC/FUC nanoparticles had a size of 320 nm and contained FUC at 47% (w/w). Efficacy was examined by the pre-treatment or post-treatment with oral administration using mice with sarcoma-180 solid tumor. In both treatments, TMC/FUC nanoparticles exhibited better suppression of tumor growth than FUC solution. The nanoparticles were considered to enhance the antitumor efficacy due to the promotion of immune induction etc. These results suggested the chitosan-based micro- or nanoparticles should be available for the enhancement of the functions of immunomostimulating agents.