Chitosan Microspheres Research Articles

Immobilisation of Cellobiose Dehydrogenase and Laccase on Chitosan Particles as a Multi-Enzymatic System for the Synthesis of Lactobionic Acid.

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.

Preparation of drug-loaded chitosan microspheres repair materials.

With the development of society and the progress of science and technology, microspheres, as a new polymer material, have been applied to all aspects of human beings. Microspheres can play a huge role in food safety, electronic technology, sewage treatment, biomedicine, etc., and are non-toxic or harmless. There are three main types of substrates for the preparation of microspheres: natural polymers, semi-synthetic polymer materials, and synthetic polymer materials. In this study, the inorganic material kaolin was modified by the emulsification-crosslinking method with chitosan and composite microspheres with large interlayer spacing were prepared, which were characterized by Fourier Transform Ioncyclotron Resonancel (FTIR) analysis and Scanning Electron Microscope (SEM). The prepared kaolin/chitosan microspheres were then placed in different amounts of aspirin and the optimal dose was investigated by encapsulation efficiency and drug loading rate. The drug release rate of 0.5 h, 1 h, 1.5 h, 2 h, 4 h, 6 h, and 12 h was then determined by simulating the human colon to determine the performance of the sustained-release drug. The experimental results showed that after the prepared composite microspheres were loaded with aspirin drug, we got the optimal dosage of 0.1 g by discussing the encapsulation efficiency and drug loading rate of the drug-loaded microspheres, and the encapsulation efficiency reached 80.80%, while the drug loading rate was 24.40%, the drug release capacity reached about 83% in about 12 hours. The research shows that the kaolin/chitosan drug-loaded microspheres prepared by the emulsification and cross-linking method are excellent drug-loading materials.

Design, Optimization and Characterization of Metformin Hydrochloride Loaded Biodegradable Microspheres using Box Behnken design for Local Delivery in Periodontitis

In the present study, metformin hydrochloride-loaded microspheres were prepared for filling into the periodontal pockets with or without grafts for the treatment of periodontitis. For this purpose, chitosan was chosen as a polymer and used at different drug/polymer ratios in the preparation of microspheres by emulsion cross-linking method. Optimization was carried out by implementing a three-factor, three-level Box–Behnken design. Mathematical models were generated by regression analysis for responses of particle size (PS) and entrapment efficiency (EE). The experimental design took into account the preparation of optimized formulation with maximum %EE and minimum PS at optimum process conditions for the microsphere formulation by reducing chemical use and formulation time, in an economical way. The optimized formulation was selected on the basis of the desirability function and was further evaluated with respect to the particle size, entrapment efficiency, in-vitro drug release, differential scanning calorimetry (DSC), fourier transform infrared (FTIR) spectroscopy and surface morphology studies. The results of release studies were evaluated kinetically and statistically. Particle size and entrapment efficiency of the selected batch were found to be in the range of 40.2 to 59.6 μm and 85 to 95%, respectively. The DSC studies revealed molecular dispersion and conversion of the drug into an amorphous form. Surface morphology of microspheres was analyzed by scanning electron microscopy (SEM) and found to be spherical in shape with a smooth surface. The mean particle size, EE, and in-vitro drug release of the optimized batch were found to be 51.4 ± 4.8 μm, 96.5 ± 1.42%, and 79.8 ± 3.1%, respectively. The release kinetics showed that the release followed the Peppas model, and the main mechanism of drug release was diffusion. These sustained-release chitosan microspheres could be a promising drug delivery system for local delivery of metformin hydrochloride in the treatment of periodontitis.

Enzymatic time-temperature indicator with cysteine-loaded chitosan microspheres/silver nanoparticles.

A time-temperature indicator (TTI) based on acid-base reaction was developed by applying a new pH dye composed of cysteine-loaded chitosan (Cys-CS) microspheres and silver nanoparticles (AgNPs). It was hypothesized that cysteine released by the disintegration of Cys-CS microspheres at a critical pH would cause AgNPs to aggregate, leading to color change. Cys-CS microspheres were produced as water-in-oil (paraffin oil, MCT oil, soybean oil) emulsions according to the KOH addition method. An enzymatic TTI was made using glucose oxidase, glucose, and catalase. Only paraffin oil produced Cys-CS microspheres (average diameter, 335 ± 100µm), whereas the others did not, probably due to saponification with KOH. FTIR analysis confirmed that cysteine was encapsulated in the microspheres. The microspheres disintegrated at pH 6.18 in a titration test. The TTI pH gradually decreased and showed a sudden color change at pH 6.10, which was similar to the critical pH of microsphere disintegration.

Study on the polypeptide-functionalized magnetic chitosan microspheres that specifically adsorb Hg (II) ions

Here, we present an effective and environmentally friendly approach for fabricating polypeptide functionalized magnetic chitosan microspheres (Fe3O4@CTS@PS) based on the effective binding of polypeptide (GCTCWCSGE) with mercury ions (Hg (II)). The morphology and component of the prepared Fe3O4@CTS@PS was characterized via scanning electronic microscopy, Fourier transform infrared spectroscopy, X-ray diffraction, thermogravimetric analysis, and vibrating sample magnetometer. Effects of the polypeptide sequence, pH, adsorption time, initial concentration, temperature on the adsorption performance and anti-interference ability and reusability were studied. The Fe3O4@CTS@PS had excellent adsorption selectivity for Hg (II) and the adsorption capacity can reach to 218.8 mg·g−1 at 318 K and pH5.0. Kinetic data was correlated well with the pseudo-second-order model and adsorption isotherm agreed well with the Langmuir isotherm model. The reusability of Fe3O4@CTS@PS was also investigated and the adsorption capacity of Fe3O4@CTS@PS for Hg(II) still remained 92% of the initial values after four adsorption-elution cycles (eluting agent was Na2S2O3). The prepared Fe3O4@CTS@PS showed excellent adsorption performance for Hg (II) in real samples (lake water, milk and nori) and was a promising adsorbent in practical applications.

Aliquat-336 impregnated chitosan microspheres for Au(I) extraction from thiosulfate solution: Preparation, adsorption mechanism, and application

In this paper, Ionic liquid Aliquat-336 impregnated chitosan microspheres (CMA) was synthesized and applied for Au(I) recovery from thiosulfate solution, which possessed adjustable particle size, good hardness and good selectivity adsorption capacity. The synthesis parameters (Aliquat-336 dosage and size) of CMA were explored. And the effects of initial solution pH, initial gold concentration, thiosulfate concentration and temperature on the gold(I) adsorption performance by CMA were was investigated systematically. The results showed CMA performed well over a wide pH range, and maximum gold adsorption capacity of 20.3 mg/g. Additionally, the gold adsorption behavior on CMA was similar to pseudo-first-order kinetics and the Langmuir model. SEM-EDS, FT-IR and XPS analyses confirmed that the mechanism of [Au(S2O3)2]3- adsorb on the CMA may be anion exchange. Notably, CMA exhibited an excellent selectivity for Au(I) in a Cu-ethylenediamine (en)-S2O32- solution. Loaded gold on CMA was easily eluted using a sodium sulfite solution, achieving a gold recovery of 62.2 %, even after four adsorption–desorption cycles. Finally, in the actual gold ore leachate adsorption and slurry adsorption method, the adsorption of gold and copper by CMA is approximately 98 % and 7 %, respectively. This study makes significant progress towards gold selective recovery in thiosulfate system, which is useful for the gold thiosulfate hydrometallurgy field.

Biological Preparation of Chitosan-Loaded Silver Nanoparticles: Study of Methylene Blue Adsorption as Well as Antibacterial Properties under Light.

Human beings have made significant progress in the medical field since antibiotics were widely used. However, the consequences caused by antibiotics abuse have gradually shown their negative effects. Antibacterial photodynamic therapy (aPDT) has the ability to resist drug-resistant bacteria without antibiotics, and as it is increasingly recognized that nanoparticles can effectively solve the deficiency problem of singlet oxygen produced by photosensitizers, the application performance and scope of aPDT are gradually being expanded. In this study, we used a biological template method to reduce Ag+ to silver atoms in situ with bovine serum albumin (BSA) rich in various functional groups in a 50 °C water bath. The aggregation of nanomaterials was inhibited by the protein's multistage structure so that the formed nanomaterials have good dispersion and stability. It is unexpected that we used chitosan microspheres (CMs) loaded with silver nanoparticles (AgNPs) to adsorb methylene blue (MB), which is both a pollutant and photosensitive substance. The Langmuir adsorption isothermal curve was used to fit the adsorption capacity. The exceptional multi-bond angle chelating forceps of chitosan make it have a powerful physical adsorption capacity, and dehydrogenated functional groups of proteins with negative charge can also bond to positively charged MB to form a certain amount of ionic bonds. Compared with single bacteriostatic materials, the bacteriostatic capacity of the composite materials adsorbing MB under light was significantly improved. This composite material not only has a strong inhibitory effect on Gram-negative bacteria but also has a good inhibitory effect on the growth of Gram-positive bacteria poorly affected by conventional bacteriostatic agents. In conclusion, the CMs loaded with MB and AgNPs have some possible applications in the purification or treatment of wastewater in the future.

Chitosan Microspheres Loaded with Curcumin and Gallic Acid: Modified Synthesis, Sustainable Slow Release, and Enhanced Biological Property.

Improving the utilization rate of loaded-drugs is of huge importance for generating chitosan-based (CS) micro-carriers. This study aims to fabricate a novel CS microspheres co-delivered curcumin (Cur) and gallic acid (Ga) to assess drug loading and release kinetics, the blood compatibility and anti-osteosarcoma properties. The present study observes the interaction between CS and Cur/Ga molecules and estimates the change in crystallinity and loading and release rate. In addition, blood compatibility and cytotoxicity of such microspheres are also evaluated. Cur-Ga-CS microspheres present high entrapment rate of (55.84 ± 0.34) % for Ga and (42.68 ± 0.11) % for Cur, possibly attributed to surface positive charge (21.76 ± 2.46) mV. Strikingly, Cur-Ga-CS microspheres exhibit slowly sustainable release for almost 7days in physiological buffer. Importantly, these microspheres possess negligibly toxic to blood and normal BMSC cells, but strong anti-osteosarcoma effect on U2OS cells. Overall, Cur-Ga-CS microspheres are promising to become a novel anti-osteosarcoma agent or sustainable delivery carrier in biomedical applications.

Collagen membrane loaded with doxycycline through hydroxypropyl chitosan microspheres for the early reconstruction of alkali-burned cornea

Corneal alkali burn is one of the most devastating ophthalmic emergencies correlated with remarkable morbidity resulting in severe visual impairment. Appropriate intervention in the acute phase determines the eventual outcome for later corneal restoration treatment. Since the epithelium plays an essential role in inhibiting inflammation and promoting tissue repair, sustained anti-matrix metalloproteinases (MMPs) and pro-epithelialization are the prior remedies during the first week. In this study, a drug-loaded collagen membrane (Dox-HCM/Col) that could be sutured to overlay the burned cornea was developed to accelerate the early reconstruction. Doxycycline (Dox), a specific inhibitor of MMPs, was encapsulated in collagen membrane (Col) through hydroxypropyl chitosan microspheres (HCM) to develop Dox-HCM/Col, affording a preferable pro-epithelialization microenvironment and an in-situ controlled release. Results showed that loading HCM into Col prolonged the release time to 7 days, and Dox-HCM/Col could significantly suppress the expression of MMP-9 and -13 in vitro and in vivo. Furthermore, the membrane accelerated the corneal complete re-epithelialization and promoted early reconstruction within the first week. Overall, Dox-HCM/Col was a promising biomaterial membrane for treating alkali-burned cornea in the early stage, and our attempt may provide a clinically feasible method for the ocular surface reconstruction.

Injectable, pro-osteogenic and antioxidant composite microspheres composed of cerium-containing mesoporous bioactive glass and chitosan for bone regeneration applications

Repair of bone defects caused by excess reactive oxygen species (ROS) remains a clinical challenge. It is essential to inhibit the overaccumulation of ROS to accelerate the bone healing process. Herein, we developed an injectable composite phenylboronic acid-modified chitosan microspheres (CSP@BG) containing cerium-doped mesoporous bioactive glass nanoparticles (Ce-MBGNs) using a W/O emulsification method and investigated the structure, antioxidant, and osteogenic activity of microspheres. We systematically evaluated the microscopic morphology and chemical structure of the microspheres using FT-IR, XRD, SEM and TGA. When the content of incorporated Ce-MBGNs ranged from 0.83 to 14.37 wt%, the microspheres retained their morphology and their particle size varied from ∼10 to ∼23 μm. In vitro tests indicated that the CSP@BG microspheres exhibited desirable antioxidant activity, scavenged a variety of ROS such as H2O2 and ·OH, and demonstrated significant DPPH radical scavenging efficiency with up to 72.8% DPPH was scavenged. In addition, the results of CCK8 assay, ALP and ARS staining, and RT-PCR assay demonstrated that the CSP@BG microspheres could significantly promote the proliferation and osteogenic differentiation of human bone marrow stromal cells by tuning the amount of Ce-MBGNs added. In conclusion, this study systematically investigated the effects of Ce-MBGNs content on the morphological characteristic, antioxidant properties, and osteogenic activity of CSP@BG microspheres. Our results demonstrate the potential of pro-osteogenic and antioxidant composite microspheres composed of Ce-MBGNs and chitosan for bone regeneration applications.

SPRAY-DRIED CHITOSAN MICROSPHERES FOR SUSTAINED DELIVERY OF TRIFLUOPERAZINE HYDROCHLORIDE: FORMULATION AND IN VITRO EVALUATION

Objective: Sustained release systems have the potential to enhance the therapeutic responses in the long-term management of psychiatric disorders. In the present study, cross-linked microspheres of the antipsychotic drug Trifluoperazine (TFP) were prepared using biodegradable polymer-chitosan and various in vitro evaluations were performed on the prepared microspheres. Methods: The spray drying technique was used to prepare TFP-loaded chitosan microspheres. Tripolyphosphate (TPP) was incorporated into the chitosan solutions as a cross-linking agent in varying concentrations. Different evaluations like production yield, encapsulation efficiency, drug-polymer compatibility, Scanning Electron Microscopy (SEM), X-ray diffraction studies (XRD), Differential Scanning Colorimetry (DSC), particle size, zeta potential analysis and in vitro drug release studies were performed on the developed formulations. Results: The formulated microparticles exhibited production yields ranging from 38.51 to 57.21% and had reasonably good encapsulation efficiencies (54.52-78.35%). The drug excipient compatibility was confirmed by Infrared Spectroscopy. All the microspheres showed positive zeta potential with a mean diameter ranging from 1.45-3.61µ. SEM images revealed the formation of spherical particles with indentations on the surface. XRD and DSC studies confirmed the presence of an amorphous form of the drug inside the microspheres. The in vitro release profile of TFP from cross-linked chitosan microspheres was influenced considerably by changing the concentration of polymer and crosslinking agent in the formulation. The drug release from (0.5%) chitosan microspheres reduced from 91% to 79%, when TPP concentration was increased from 10% w/w to 30% w/w. All the formulations clearly showed a burst release of the drug in the initial hours and a subsequent sustained release profile. Conclusion: The results of this study suggest that TPP crosslinked spray-dried chitosan microparticles could be a promising method for developing a long-acting drug delivery system intended to effectively treat schizophrenia.

Yb(OTf)3 Anchored on Crosslinked Chitosan Microsphere: A Green Heterogenized Catalyst for the Synthesis of Bispiro‐Fused Heterocycles

AbstractUsing renewable biomass chitosan as a raw material, crosslinked chitosan microsphere (CCM) was prepared by inverse suspension, which was then immersed in the ethanol solution of Yb(OTf)3 to fabricate CCM‐supported Yb(OTf)3 (Yb(OTf)3@CCM). The three‐component [3+2] cycloaddition of isatins, tetrahydroisoquinolines and 5‐alkenyl rhodanines was developed with Yb(OTf)3@CCM as a green heterogeneous catalyst, which gave access to a suite of architecturally complex bispiro‐fused heterocycles merging four pharmacophores with moderate to excellent yields (50–96 %) and diastereoselectivities (up to 99 : 1 dr). The reaction mechanism was preliminarily clarified by controlled experiments and dynamic high‐resolution mass spectrometry studies. The synthetic potential of this protocol was proved by a gram‐scale reaction which furnished the product with comparable results (85 % yield and 72 : 28 dr). Moreover, the catalyst could be recovered just through filtering, washing and drying process, and reused five times with the catalytic activity remaining in an acceptable range (from 93 % to 73 % yield).

Chitosan derived efficient and stable Pd nano-catalyst for high efficiency hydrogenation

The design and development of green and efficient supported catalysts is the frontier direction in the field of green synthesis, which conforms to the strategic concept of green sustainable chemistry and “carbon neutrality”. Herein, we used a renewable resource chitosan (CS) derived from seafood wastes of chitin as carriers to design two different chitosan-supported palladium (Pd) nano-catalysts through different activation methods. The Pd particles were firmly and uniformly dispersed on the chitosan microspheres due to the interconnected nanoporous structure and functional groups of chitosan, proved by diverse characterizations. The chitosan supported catalysts (Pd@CS) was applied to hydrogenation of 4-nitrophenol, which showed competitive catalytic activity compared to commercial Pd/C, un-supported nano-Pd and Pd(OAc)2 catalysts, as well as excellent catalytic activity, good reusability, long-life and broad applicability in selective hydrogenation of aromatic aldehydes, suggesting potential of applications in green industrial catalysis.

Preparation and Characterization of Eudragit Coated Chitosan Microspheres of Anticancer Drug for Colon Cancer

Carrier technology provides an interesting as well as an intelligent approach for the delivery of drug. It offers delivery of drug by coupling the drug to a carrier particle such as microspheres, mucoadhesive microspheres, nanoparticles, liposomes, etc. Mucoadhesive microspheres constitute an important part of this particulate drug delivery system because of their small size and other efficient properties. Mucoadhesive microspheres play a vital role in the novel drug delivery system. Some drug delivery problems are overcome by producing controlled drug delivery system which enhances the therapeutic efficacy of a drug. From various approaches one approach is to using mucoadhesive microsphere as a carrier system for drug delivery. Mucoadhesive microspheres exhibit a prolonged residence time at the site of application or absorption and facilitate an intimate contact with the underlying absorption surface and thus contribute to improved and better therapeutic performance of drugs and also mucoadhesive microspheres have advantages like efficient absorption and enhanced bioavailability of the drugs due to a high surface to volume ratio, a much more intimate contact with the mucus layer, controlled and sustained release of drug from dosage form and specific targeting of drugs to the absorption site. Mucoadhesive microspheres have been developed for oral, buccal, nasal, ocular, rectal and vaginal for either systemic or local effects.

Removal of BB41 dye molecules onto cross-linked chitosan microspheres: synthesis, characterization, and sorption/desorption

Removal of BB41 dye molecules onto cross-linked chitosan microspheres: synthesis, characterization, and sorption/desorption

Hydrophilic molecularly imprinted chitosan microspheres based on deep eutectic solvents for micro-solid phase extraction of catechin

Hydrophilic molecularly imprinted chitosan microspheres (HMICS) were synthesized using deep eutectic solvents (DESs)-(3-aminopropyl) triethoxysilane (APTES) as co-functional monomer for the extraction of catechin from green tea with micro-solid phase extraction (micro-SPE). Various factors were studied to optimize the extraction condition during extraction process. The actual extraction amount under the optimal conditions (amount of adsorbent (20 mg), type and volume of washing (acetone, 1.2 mL) and eluting solvent (acetone/acetic acid, 1.0 mL), extraction time (30 min), extraction temperature (40 °C), and sample pH (4)) were obtained at 97.06 mg·g−1. The catechin recovery ranged with ranged with limit of detection (LOD) within 0.09–0.24 µg·mL−1, and limit of quantification (LOQ) within 0.18–0.28 µg·mL−1. From the experimental results in this system, the HMICS was proved to have higher extraction capacity, improving as a promising adsorbent for the extraction of catechin.

Ink Based on the Tunable Swollen Microsphere for a 3D Printing Hydrogel with Broad-Range Mechanical Properties.

The development of the effective 3D printing strategy for diverse functional monomers is still challenging. Moreover, the conventional 3D printing hydrogels are usually soft and fragile due to the lack of an energy dissipation mechanism. Herein, a microsphere mediating ink preparation strategy is developed to provide tailored rheological behavior for various monomer direct ink writings. The chitosan microspheres are used as an exemplary material due to their tunable swelling ratio under the acid-drived electrostatic repulsion of the protonated amino groups. The rheological behaviors of the swollen chitosan microsphere (SCM) are independent on the monomer types, and various functional secondary polymers could be carried at a wide loading ratio by the acid driving. The SCM reinforces the hydrogel as the sacrificial bonds. With the adjustable composition, the 3D printing hydrogel mechanical properties are tunable in wide windows: strength (0.4-1.01 MPa), dissipated energy (0.11-3.25 MJ m-3), and elongation at break (47-626%). With the excellent printing and mechanical properties, the SCM inks enable multi-functional integration for soft device production, such as 4D printing robots and wearable strain sensors. We anticipate that this microsphere mediating 3D printing strategy can inspire new possibilities for the design of the robust hydrogels with a broad range of functionalities and mechanical performances.

Poly(β-amino ester) Dual-Drug-Loaded Hydrogels with Antibacterial and Osteogenic Properties for Bone Repair.

In this study, we developed a poly(β-amino ester) (PBAE) hydrogel for the double release of vancomycin (VAN) and total flavonoids of Rhizoma Drynariae (TFRD). VAN was covalently bonded to PBAE polymer chains and was released to enhance the antimicrobial effect first. TFRD chitosan (CS) microspheres were physically dispersed in the scaffold, TFRD was released from the microspheres, and osteogenesis was induced subsequently. The scaffold had good porosity (90.12 ± 3.27%), and the cumulative release rate of the two drugs in PBS (pH 7.4) solution exceeded 80%. In vitro antimicrobial assays demonstrated the antibacterial properties of the scaffold against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). Besides these, cell viability assays indicated that the scaffold had good biocompatibility. Moreover, alkaline phosphatase and matrix mineralization were expressed more than in the control group. Overall, cell experiments confirmed that the scaffolds have enhanced osteogenic differentiation capabilities. In conclusion, the dual-drug-loaded scaffold with antibacterial and bone regeneration effects is promising in the field of bone repair.

Chitosan grafted with crown ether with high selectivity and adsorption on lithium-ion

Currently, Lithium is the lightest metal known in nature, which is widely applied in most walks of life. However, the present storage of lithium resources in the world is far from meeting the consumption market surge demand for lithium resources. Liquid lithium resources such as Salt Lake brine and seawater brine will become the primary source and inevitable choice for lithium extraction in the future due to a large amount of lithium, and its recovery requires a simple and effective process. This study synthesized TEG4MEC, a pseudo-crown ether monomer with a ring unit, to achieve effective Lithium-ion (Li+) recognition through specific interaction with Li+. Then, the TEG4MEC monomer was grafted onto the surface of cross-linked chitosan microspheres (CCS) by surface initiation polymerization. A series of static and dynamic adsorption studies showed that the pH value of the solution had a significant effect on Li+ adsorption. For CCS-TEG4MEC microspheres, the best adsorption effect was observed at pH = 7.0. The maximum adsorption capacity of Li+ on CCS-TEG4MEC microspheres obtained by Langmuir isotherm fitting is 156.16 mg g−1. In addition, CCS-TEG4MEC microspheres also showed effective regeneration performance and highly stable adsorption capacity, which could be reused.

Maximising olive oil by‐products

Maximising olive oil by‐products