Calcium Alginate Microspheres Research Articles

Mechanical investigation of a Tandem embolization-visualization system for minimally invasive procedures

Transcatheter arterial embolization is a minimally invasive intervention process in which the blood supply to a tumor or an abnormal area of tissue is blocked. One of the most commonly used embolic agents in clinics is microsphere (MS). In order to understand the flow behavior of microspheres in arteries, it is essential to study their mechanical properties systematically. In this work, calcium-alginate MSs with varying calcium concentrations were synthesized using a coaxial airflow method. Indocyanine green (ICG) was added as a fluorescent dye. The effect of ICG concentration change on microspheres was investigated by studying morphology, imageability, rheology, and swelling behavior. Then the effect of calcium chloride concentration change on microspheres was studied by conducting rheological tests, atomic force microscopy tests, hemolysis assay, and thrombogenicity assay. Results showed that microspheres with higher ICG concentrations have longer lasting fluorescence and lower storage modulus (G′). Higher concentrations of calcium chloride led to higher G′, while the local Young's modulus obtained by AFM test was not significantly affected. The MSs with and without ICG showed good hemocompatibility and thrombogenicity.

Oral Microto-Nano Genome-Editing System Enabling Targeted Delivery and Conditional Activation of CRISPR-Cas9 for Gene Therapy of Inflammatory Bowel Disease.

The potent CRISPR-Cas9 technology can correct genes in human mutated cells to achieve the treatment of multiple diseases, but it lacks safe and effective delivery systems. Herein, we proposed an oral microto-nano genome-editing system aiming at the enteric excessive level of TNF-α for specific gene therapy of inflammatory bowel disease (IBD). This editing system facilitated the assembly of Cas9/sgRNA ribonucleoprotein (RNP) into nanoclusters (NCs) through the bridging of disulfide bonds. RNP-NCs were subsequently encapsulated within inflammatory cell-targeted lipopolysaccharide-deleted outer membrane vesicles (dOMVs) sourced from Escherichia coli Nissle 1917, which were further shielded by an outer layer of calcium alginate microspheres (CAMs). By leveraging the protection effect of CAMs, the oral administration system withstood gastric acid degradation upon entry into the stomach, achieving targeted delivery to the intestines with high efficiency. As the pH gradually rose, the microscale CAMs swelled and disintegrated, releasing nanoscale RNP-NCs encapsulated in dOMVs into the intestines. These RNP-NCs@dOMVs could traverse the mucosal barrier and target inflammatory macrophages where conditionally activated Cas9/sgRNA RNPs effectively perform genomic editing of TNF-α within the nucleus. Such oral microto-nano genome-editing systems represent a promising translational platform for the treatment of IBD.

Development of Alginate-Based Biodegradable Radioactive Microspheres Labeled with Positron Emitter through Click Chemistry Reaction: Stability and PET Imaging Study.

Biodegradable radioactive microspheres labeled with positron emitters hold significant promise for diagnostic and therapeutic applications in cancers and other diseases, including arthritis. The alginate-based polymeric microspheres offer advantages such as biocompatibility, biodegradability, and improved stability, making them suitable for clinical applications. In this study, we developed novel positron emission tomography (PET) microspheres using alginate biopolymer radiolabeled with gallium-68 (68Ga) through a straightforward conjugation reaction. Polyethylenimine (PEI)-decorated calcium alginate microspheres (PEI-CAMSs) were fabricated and further modified using azadibenzocyclooctyne-N-hydroxysuccinimide ester (ADIBO-NHS). Subsequently, azide-functionalized NOTA chelator (N3-NOTA) was labeled with [68Ga]Ga to obtain [68Ga]Ga-NOTA-N3, which was then reacted with the surface-modified PEI-CAMSs using strain-promoted alkyne-azide cycloaddition (SPAAC) reaction to develop [68Ga]Ga-NOTA-PEI-CAMSs, a novel PET microsphere. The radiolabeling efficiency and radiochemical stability of [68Ga]Ga-NOTA-PEI-CAMSs were determined using the radio-instant thin-layer chromatography-silica gel (radio-ITLC-SG) method. The in vivo PET images were also acquired to study the in vivo stability of the radiolabeled microspheres in normal mice. The radiolabeling efficiency of [68Ga]Ga-NOTA-PEI-CAMSs was over 99%, and the microspheres exhibited high stability (92%) in human blood serum. PET images demonstrated the stability and biodistribution of the microspheres in mice for up to 2 h post injection. This study highlights the potential of biodegradable PET microspheres for preoperative imaging and targeted radionuclide therapy. Overall, the straightforward synthesis method and efficient radiolabeling technique provide a promising platform for the development of theranostic microspheres using other radionuclides such as 90Y, 177Lu, 188Re, and 64Cu.

Fabrication of Ca-alginate microspheres by diffusion-induced gelation in double emulsion droplets for oral insulin

Sodium alginate has good biocompatibility and is widely used in the study of drug carriers. In this paper, a method to prepare calcium alginate microspheres with high sphericity based on double emulsion droplets was proposed, in which sodium alginate is used as the innermost phase. By adjusting the density of the system, the double-emulsion droplets could be suspended in the collecting solution, leading to the homogeneous reaction between the sodium alginate droplets and the calcium ions. By changing the flow rate, the size of the droplets could be changed, and by changing the concentration of calcium ions in the collecting solution, the sphericity of the calcium alginate microspheres could be changed. Then the swelling properties and drug release properties of calcium alginate microspheres were determined. The drug delivery study revealed that the insulin-loaded Ca-Alginate microspheres were able to decrease blood glucose by 41.4 % after oral administration to mice. Thus, the Ca-Alginate microsphere is a suitable candidate for controlled pH-sensitive drug delivery.

Calcium alginate microspheres coated by bio-based UV-cured resin with high water retention performance

Calcium alginate microspheres coated by bio-based UV-cured resin with high water retention performance

Oral alginate microspheres for the efficient site-specific delivery of epidermal growth factor attenuated murine ulcerative colitis via repairing the mucosal barrier

Ulcerative colitis (UC) is a chronic bowel inflammatory disease affecting the colorectum. Epidermal growth factor (EGF) has been demonstrated to be effective to counteract UC. However, there exists the gastrointestinal challenges such as stomach acid, enzyme and bile salts for oral delivery of EGF. Herein, calcium alginate microsphere was prepared by the microfluidic technique to encapsulate EGF. The morphology of EGF-loaded microsphere (MS-EGF) was spherical and its average particle size was 80 ± 23 μm. The encapsulation efficiency of EGF was reaching to 93.8 % ± 1.6 %. In vitro release experiments showed that MS-EGF presented the good pH-sensitive properties, that was, it could effectively resist the gastric acid and small intestinal fluids, and undergone the rapid dissolution in the artificial colon fluid. In vitro cellular experiments demonstrated that the bioactivity of EGF was well preserved by microsphere. Moreover, in vivo murine colitis model showed that MS-EGF presented the obvious colitis alleviation. Furthermore, the colonic morphology of colitis mice was effectively recovered and the tight junction between the gut epithelium was obviously repaired. In conclusion, calcium alginate microsphere might be a promising vehicle of EGF for UC treatment.

Development of a tobramycin-loaded calcium alginate microsphere/chitosan composite sponge with antibacterial effects as a wound dressing

Traditional dressings exhibit several disadvantages, as they frequently lead to bacterial infections, cause severe tissue adhesion and perform a relatively single function. Therefore, in this study, a composite sponge dressing with antibacterial properties and excellent physicochemical properties was developed. Six groups of tobramycin-loaded calcium alginate microspheres were prepared by changing the amount of tobramycin added, and the optimal group was selected. Then, seven groups of tobramycin-loaded calcium alginate microsphere/chitosan composite sponges were fabricated via a solvent blending process and a freeze-drying method. The surface morphology, physicochemical properties, in vitro degradation properties, in vitro drug release properties, antibacterial properties and cytotoxicity of the composite sponges were examined. Group 3.0 contained the best microspheres with the largest drug loading capacity, good swelling performance and cumulative drug release rate, obvious and sustained antibacterial activity, and good cytocompatibility. The tobramycin-loaded calcium alginate microsphere/chitosan composite sponges exhibited three-dimensional porous structures, and their porosity, swelling rate, water absorption and water retention rates and water vapor transmission rate met the standards needed for an ideal dressing. The comprehensive performance of the sponge was best when 20 mg of drug-loaded microspheres was added (i.e. group 20). The cumulative drug release rate of the sponge was 29.67 ± 4.14% at 7 d, the diameters of the inhibition zones against the three bacteria were greater than 15 mm, and L929 cell proliferation was promoted. These results demonstrated that the tobramycin-loaded calcium alginate microsphere/chitosan composite sponge with 20 mg of tobramycin-loaded microspheres shows promise as a dressing for infected wounds.

Co-immobilization of laccase-mediator system to catalyze the synthesis of theaflavins from tea polyphenols

The co-immobilized laccase-mediator system (LMS) has broad development prospects in the fields of biocatalysis, biochemistry, and environmental remediation. In this study, laccase and mediator molecules were co-immobilized in functionally modified calcium alginate microspheres to improve their catalytic activity and stability and to systematically characterize the physicochemical properties and evaluate the catalytic performance of the co-immobilized laccase-mediator system. The co-immobilized LMS was used to catalyze the synthesis of theaflavins (TFs) from tea polyphenols, improve the catalytic efficiency, realize the recycling of the system, and explore the safety of the catalytic products. The results showed that the catalytic efficiency of the co-immobilized LMS was significantly improved and the relative activity remained above 50% after 10 cycles. The in vitro safety of the catalytic product was verified by Human hepatocellular carcinoma (HepG2) cell-related indexes. The results show that the co-immobilized laccase mediator system has great development potential in the industrial application of theaflavins.

Eco-friendly calcium alginate microspheres enable enhanced profile control and oil displacement

Polymer microspheres (PMs), such as polyacrylamide, have been widely applied for enhanced oil recovery (EOR), yet with environmental concerns. Here, we report a microfluid displacement technology containing a bio-based eco-friendly material, i.e., calcium alginate (CaAlg) microspheres for EOR. Two dominant mechanisms responsible for EOR over CaAlg fluid have been verified, including the microscopic oil displacement efficacy augmented by regulating capillary force (determined by the joint action of interfacial tension and wettability between different phases) and macroscopic sweep volume increment through profile control and mobility ratio reduction. This comprehensive effectiveness can be further impacted when the CaAlg microsphere is embellished ulteriorly by using appropriate amount of sodium dodecyl sulfonate (SDS). The core flooding and nuclear magnetic resonance (NMR) tests demonstrate that CaAlg-SDS microsphere can balance the interphase property regulation (wettability alteration and IFT reduction) and rheology properties, enabling simultaneous profile control and oil displacement. Excessive introduction of SDS will have a negative impact on rheological properties, which is not favored for EOR. Our results show that the involvement of 4-mM SDS will provide the best behavior, with an EOR rate of 34.38%. This cost-effective and environmentally-friendly bio-microsphere-based microfluidic displacement technology is expected to achieve “green” oil recovery in future oilfield exploitation.

Controlled production of liposomes with novel microfluidic membrane emulsification for application of entrapping hydrophilic and lipophilic drugs

In view of the limitations in the reported methods for the preparation of liposomes, a new microfluidic membrane emulsification device was innovatively designed and fabricated to investigate the effects of prescription factors and process parameters on the formation of liposomes based on a liposome prescription suitable for encapsulating nucleotides. It was shown that precise control of liposome particle size can be achieved by adjusting prescription factors and process parameters, and the obtained liposomes have good stability. In this study, we efficiently encapsulated nicotinamide mononucleotide (NMN) and honokiol to achieve co-delivery and graded release of hydrophilic and hydrophobic drugs, and its inhibitory activity against colon cancer cells was significantly higher than that of the free drug. What’s more, a new high-performance liquid chromatographic method was built up to determine the encapsulation rate of NMN liposomes, which would be useful for the development of NMN drug applications. Notably, we also extended the technique to drug delivery microsphere platform construction to achieve homogeneous and controllable preparation of high-viscosity calcium alginate microspheres. This study is a valuable guide for the construction of drug delivery system platforms and has promising applications.

Effect of lignocellulose/montmorillonite immobilized Bacillus sp. on monosodium glutamate wastewater.

A group of Bacillus sp. was extracted from monosodium glutamate wastewater. Lignocellulose/montmorillonite composite was selected as the carrier. Lignocellulose/montmorillonite composite immobilized Bacillus sp./calcium alginate microspheres were prepared by immobilized microorganism techniques. The microspheres were used to treat monosodium glutamate wastewater with significantly reduced ammonia nitrogen (NH3-N) and chemical oxygen demand (COD) concentrations. The optimum preparation conditions of microspheres in the treatment of NH3-N and COD of monosodium glutamate wastewater were studied. The concentration of sodium alginate was 2.0 wt%, lignocellulose/montmorillonite was 0.06 wt%, Bacillus sp. was 1.0 wt%, CaCl2 solution was 2.0 wt%, coagulation time was 12h, and the removal capacities of NH3-N and COD were 44832 and 78345mg/L, respectively. The surface structure, element content, functional group change, and crystal structure of the microspheres were characterized by SEM, EDS, and other methods. The results showed that the -COOH in lignocellulose/montmorillonite and the -OH in the Bacillus sp. form intermolecular hydrogen bonds. The Si-O and Al-O bonds in lignocellulose/montmorillonite reacted with sodium ions in sodium alginate. New crystal structures appear inside the material after crosslinking, and the microspheres was formed. Thus, the study has shown that the microspheres were successfully prepared and contributes to the treatment of NH3-N and COD in monosodium glutamate wastewater. This work can provide an interesting strategy for the removal of COD and NH3-N in industrial wastewater by reasonably combining bio-physicochemical processes.

Encapsulation of activated carbon into calcium alginate microspheres toward granular-activated carbon adsorbents for elemental mercury capture from natural gas.

Activated carbon (AC) is an effective adsorbent for removing environmental pollutants. However, the traditional powder form of AC shows difficulty in handling during application which widely limits its utilization on the industrial scale. Herein, to avoid such limitation, traditional AC powder was encapsulated into calcium alginate (CA) microspheres. Calcium alginate/activated carbon (CAA) composite microspheres were prepared via cross-linking of sodium alginate/activated carbon composite solutions in a calcium chloride solution. Furthermore, in order to boost adsorption affinity of CAA composite microspheres toward elemental mercury (Hg°), ammonium iodide (NH4I)-treated calcium alginate/activated carbon (NCA) composite microspheres were obtained by a simple impregnation method using NH4I treatment. The morphological, structural, and textural properties of the microspheres were characterized and their Hg° adsorptive capacity was tested at different temperatures. Interestingly, the maximum adsorption capacity of NCA adsorbent composite microspheres was determined as 36,056.5μg/g at a flow rate of 250mL/min, temperature of 25°C, and 500μg/Nm3 of Hg° initial concentration. The Gibbs free energy (ΔG°) for NCA adsorbent composite microspheres varied from - 8.59 to - 10.54kJ/mol indicating a spontaneous adsorption process with an exothermic nature. The experimental Hg° breakthrough curve correlated well with Yoon‒Nelson and Thomas models. The breakthrough time (tb) and equilibrium time (te) were found to be 7.5days and 23days, respectively. Collectively, the findings of this work indicate a good feasibility of using NCA composite microspheres as potential adsorbents for removing Hg° from natural gas.

Preparation of thrombin-loaded calcium alginate microspheres with dual-mode imaging and study on their embolic properties in vivo

Transcatheter arterial embolization (TAE) has played a huge role in the interventional treatment of organ bleeding and accidental bleeding. Choosing bio-embolization materials with good biocompatibility is an important part of TAE. In this work, we prepared a calcium alginate embolic microsphere using high-voltage electrostatic droplet technology. The microsphere simultaneously encapsulated silver sulfide quantum dots (Ag2S QDs) and barium sulfate (BaSO4), and fixed thrombin on its surface. Thrombin can achieve an embolic effect while stopping bleeding. The embolic microsphere has good near-infrared two-zone (NIR-II) imaging and X-ray imaging effects, and the luminous effect of NIR-II is better than that of X-rays. This breaks the limitations of traditional embolic microspheres that only have X-ray imaging. And the microspheres have good biocompatibility and blood compatibility. Preliminary application results show that the microspheres can achieve a good embolization effect in the ear arteries of New Zealand white rabbits, and can be used as an effective material for arterial embolization and hemostasis. This work realizes the clinical embolization application of NIR-II combined with X-ray multimodal imaging technology in biomedical imaging, achieving complementary advantages and excellent results, more suitable for studying biological changes and clinical applications.

Litchi-like silver nanoparticles immobilized in microspheres for effective bacteriostasis, rapid hemostasis, and wound healing

Metal nanoparticles, particularly silver nanoparticles (AgNs), exhibit excellent antibacterial properties. However, their high mobility and Ag+ release rate can damage normal tissues and cells. Therefore, their application in wound healing is limited. Reducing Ag+ to AgNs using tannic acid (TA) and Fe complexes (TA/Fe) could effectively prevent the migration of AgNs and slow the release of Ag+ to achieve effective inhibition of bacteria. Ag+ was reduced to AgNs using TA/Fe coating on the surface of calcium alginate and silk fibroin peptide microspheres (CA/SP) to prepare novel litchi-like microspheres (CA/SP@AgNs). CA/SP@AgNs showed good biocompatibility. The growth and reproduction of Staphylococcus aureus and Pseudomonas aeruginosa were completely inhibited at a CA/SP@AgNs concentration of 20 mg/mL. The redox reaction of Ag+ with TA/Fe resulted in the oxidation of Fe2+ to Fe3+. The hemostatic ability of CA/SP@AgNs was significantly enhanced owing to the good coagulation ability of TA/Fe3+ in the blood, which reduced the bleeding time and hemostatic volume of the femoral artery to 109 s and 0.115 g, respectively. Therefore, TA/Fe-modified microspheres are good carriers of AgNs that can be used for efficient bacteriostasis, rapid hemostasis, and wound healing.

Gelatin/alginate-based microspheres with sphere-in-capsule structure for spatiotemporal manipulative drug release in gastrointestinal tract

Microsphere with sphere-in-capsule structure is a multi-drugs delivery system to achieve the purpose of combination therapy. In this paper, we have prepared gelatin/alginate-based microspheres with sphere-in-capsule structure by a relatively fast, simple, and easily large-scale industrialized emulsification method for spatiotemporal manipulative drug release in gastrointestinal tract. Calcium alginate microspheres encapsulated with bovine serum albumin (BSA) were first prepared as inner microspheres, and then inner microspheres and ranitidine hydrochloride (RH) were co-encapsulated by gelatin microspheres to form double-layer microspheres with sphere-in-capsule structure. The size and distribution of microspheres can be easily controlled by emulsifying conditions. The microspheres with sphere-in-capsule structure displayed desirable encapsulation efficiency of BSA (61.52 %) and RH (56.07 %). The in vitro simulated drug release showed the spatiotemporal release feature of microspheres with sphere-in-capsule structure. In the specific simulated fluid, the release behavior and cumulative release of RH (sustainedly released 95 % in simulated gastric fluid) and BSA (rapidly released 73 % in simulated intestinal fluid) were different. The drug release mechanisms were analyzed to determine RH and BSA's release behavior. Overall, the microspheres with sphere-in-capsule structure have the potential application of spatiotemporal manipulative drug delivery in the gastrointestinal tract.

On-demand preparation of calcium alginate microspheres via piezoelectric microfluidics

Calcium alginate microspheres (CAMs) have attracted extensive attention as a novel drug carrier due to their cheapness, biodegradability, biocompatibility and nontoxicity. The existing preparation technologies of CAMs require complex process steps and involve multiple types of equipment, which are difficult to achieve the real-time and on-demand supply of microspheres in micro-reaction experiments. In this work, CAMs for prolonged drug release are prepared by the designed piezoelectric microfluidic devices using sodium alginate (NaAlg) and calcium chloride (CaCl 2 ). Specifically, the on-demand CAMs are synthesized timely by piezoelectric micro-jet followed by the transportation of piezoelectric micro-pump. Furthermore, various solution concentrations, main parameters of excitation signal and different nozzle diameters are evaluated in terms of size, morphology and drug release rate. The control method of CAMs’ size is obtained based on the multi-physics coupling analysis. Experimental results show that the doxorubicin hydrochloride loaded CAMs (DOX-CAMs) which can be prepared on demand, have excellent uniformity and dispersion, and the minimum average particle size is about 81.9 µm. The controlled drug release rate of DOX-CAMs reaches 83.2 % after 24 h. Moreover, the piezoelectric microfluidic devices and corresponding control methods may have potentials to be adapted for synthesizing other inorganic composite microspheres. • Piezoelectric microfluidics realize the timely supply of microspheres on demand. • The control strategy of microspheres was obtained by simulation analysis. • Preparation of high-quality microspheres with uniformity and dispersion. • Microspheres have excellent drug release performance.

The calcium alginate-immobilized Co-g-C3N4 composite microspheres as an efficient mediator to activate peroxymonosulfate for degrading organic pollutants

Poor water stability and difficult separation severely limited the application of Co-based catalysts in persulfate activation. Herein, for the first time, the calcium alginate-immobilized Co-g–C3N4–2 composite microspheres were prepared by a feasible method. Notably, embedding Co ion into g-C3N4 can improve its specific surface area and electrochemical activities. More significantly, as-prepared Co-g–C3N4–2 microsphere presented excellent catalytic performance in PMS activation for the degradation of TC. For the activation mechanisms of PMS over Co-g–C3N4–2 microspheres, the calcium alginate microspheres could mediate the direct electron transfer between TC and PMS, while both radical and nonradical pathways were involved in the activation of PMS over Co-g–C3N4–2. Meanwhile, SO4•−, OH•, O2•− and 1O2 were major reactive oxygen species formed in the Co-g–C3N4–2 microsphere/PMS system. Proposed Co-g–C3N4–2 microsphere/PMS system still exhibited great degradation ability towards TC over a wide pH range, and co-existing anions had weak influence on TC degradation over Co-g–C3N4–2 microsphere/PMS system. Moreover, the construction of Co-g–C3N4–2 microspheres not only avoided the release of metal ion from catalyst, but also provided convenience for the recovery of catalyst. In short, current work shared some novel insights into the application of heterogeneous catalysis in persulfate activation for wastewater treatment.

Applicability of alginate-based composite microspheres loaded with aqueous extract of Stevia rebaudiana Bertoni leaves in food and pharmaceutical products

To preserve its favorable health and nutritional qualities under processing conditions and oral ingestion, Stevia rebaudiana Bertoni leaf aqueous extract was encapsulated in composite microspheres based on calcium alginate. The addition of other biopolymers to alginate (ALG) (xanthan gum (XG), casein (CA)) influenced molecular interactions (mainly hydrogen bonding and electrostatic interactions) between microsphere constituents causing the change in microsphere structure and thus physicochemical properties (encapsulation effectiveness and capacity, surface morphology, swelling, stability) as well as the release of total polyphenols (TPC) in distilled water, NaCl solutions and in simulated gastrointestinal fluids.The extent of crosslinking of calcium alginate was altered by blending with XG, CA, or XG + CA, but this did not affect the control mechanism of TPC release detected as diffusion. Results revealed the unsuitability of calcium alginate microspheres for implementation in food products with high water content, while composite microspheres showed desired reduction in TPC release. The best performance (the slowest release and the amount released) for implementation in functional food products containing NaCl exhibited composite microspheres with ALG + XG + CA. The desired prevention of microsphere degradation in simulated gastro fluids was achieved with ALG + XG + CA microspheres, while in simulated intestinal fluids all microspheres were decomposed and completely released TPC.

Development and Characterization of a Novel Soil Amendment Based on Biomass Fly Ash Encapsulated in Calcium Alginate Microspheres.

Biomass fly ash (BFA) from a biomass cogeneration plant was encapsulated into calcium alginate microspheres (ALG/Ca) and characterized. An FTIR analysis indicated that BFA loading weakened molecular interactions between ALG/Ca constituents (mainly hydrogen bonding and electrostatic interactions), thus changing the crosslinking density. SEM and AFM analyses revealed a wrinkled and rough surface with elongated and distorted granules. The in vitro release of BFA’s main components (K, Ca, and Mg) was controlled by diffusion through the gel-like matrix, but the kinetics and released amounts differed significantly. The smaller released amounts and slower release rates of Ca and Mg compared to K resulted from the differences in the solubility of their minerals as well as from the interactions of divalent cations with alginate chains. The physicochemical properties of the novel microsphere formulation reveal significant potential for the prolonged delivery of nutrients to crops in a safe manner.

PH-Responsive Calcium Alginate Microspheres Modified with Chitosan for Immobilization of Antibiotic Cefotaxime

pH-Responsive Calcium Alginate Microspheres Modified with Chitosan for Immobilization of Antibiotic Cefotaxime