Xiubin Xu

Injectable and Self-Healing Carbohydrate-Based Hydrogel for Cell Encapsulation

With the fast development of cell therapy, there has been a shift toward the development of injectable hydrogels as cell carriers that can overcome current limitations in cell therapy. However, the hydrogels are prone to damage during use, inducing cell apoptosis. Therefore, this study was carried out to develop an injectable and self-healing hydrogel based on chondroitin sulfate multiple aldehyde (CSMA) and N-succinyl-chitosan (SC). By varying the CSMA to SC ratio, the hydrogel stiffness, water content, and kinetics of gelation could be controlled. Gelation readily occurred at physiological conditions, predominantly due to a Schiff base reaction between the aldehyde groups on CSMA and amino groups on SC. Meanwhile, because of the dynamic equilibrium of Schiff base linkage, the hydrogel was found to be self-healing. Cells encapsulated in the hydrogel remained viable and metabolically active. In addition, the hydrogel produced minimal inflammatory response when injected subcutaneously in a rat model and showed biodegradability in vivo. This work establishes an injectable and self-healing hydrogel derived from carbohydrates with potential applications as a cell carrier and in tissue engineering.

Biomass-based multifunctional fertilizer system featuring controlled-release nutrient, water-retention and amelioration of soil

In an effort to enhance the efficiency of fertilizer use and minimize adverse environmental effects, a novel biomass-based, multifunctional controlled-release fertilizer (BMCF) was prepared to improve nutrient use efficiency and enhance crop production systems for more sustainable agriculture practices. The fertilizer design included natural attapulgite as a matrix, co-granulated ammonium zinc phosphate and urea as fertilizer core, cellulose acetate butyrate (CAB) as an inner coating, and a carboxymethyl chitosan-g-poly(acrylic acid)/attapulgite (CMCS-g-PAA/APT) superabsorbent composite as an outer coating. The effect of an APT matrix, CAB inner coating and superabsorbent composite outer coating on nutrient release rate was investigated. The influence of the BMCF on water-holding and water-retention capacity of soil samples was determined. The degradation behavior of the CMCS-g-PAA/APT outer coating in soil solution was evaluated. The experimental results indicated that the product prepared by a simple and economical method can effectively reduce N leaching loss and runoff, improve soil moisture retention capacity, and ameliorate soil acidity and alkalinity.

Multifunctional Environmental Smart Fertilizer Based on l-Aspartic Acid for Sustained Nutrient Release

Fertilizer is one of the most important elements of modern agriculture. However, conventional fertilizer, when applied to crops, is vulnerable to losses through volatilization, leaching, nitrification, or other means. Such a loss limits crop yields and pollutes the environment. In an effort to enhance nutrient use efficiency and reduce environmental pollution, an environmental smart fertilizer was reported in the current study. Poly(aspartic acid) and a degradable macro-cross-linker based on l-aspartic acid were synthesized and introduced into the fertilizer as a superabsorbent to improve the fertilizer degradability and soil moisture-retention capacity. Sustained release behavior of the fertilizer was achieved in soil. Cumulative release of nitrogen and phosphorus was 79.8% and 64.4% after 30 days, respectively. The water-holding and water-retention capacities of soil with the superabsorbent are obviously higher than those of the control soil without superabsorbent. For the sample of 200 g of soil with 1.5 g of superabsorbent, the water-holding capacity is 81.8%, and the water-retention capacity remains 22.6% after 23 days. All of the current results in this study indicated that the as-prepared fertilizer has a promising application in sustainable modern agriculture.

Synthesis of a starch derivative and its application in fertilizer for slow nutrient release and water-holding

With the increasing public concern toward human health, environmental protection, and natural resource sustainability, there is a shift toward the development of environmentally friendly fertilizers based on biomass. In this study, a coated fertilizer system based on starch acetate (SA) and weakly cross-linked carboxymethyl starch/xanthan gum (CMS/XG) was developed to improve biomass utilization efficiency and reduce environmental pollution. The coated fertilizer with a diameter in the range of 2.5–3.0 mm possesses low moisture content and high mechanical hardness. Nutrient nitrogen reached a steady state of releasing equilibrium within 20 days and the release behaviour depended on the coating thickness and the plasticizer content of the SA film. Soil water-holding capacity determination showed that soil/coated fertilizer mixtures retained more water than the control soil, and the water content increased with increasing amount of the coated fertilizer in the soil. The experimental data indicated that the products based on starch derivatives as coating materials have preferable slow-release performance and the introduction of the natural polymers can improve biomass utilization efficiency, reduce nutrient loss and improve water use efficiency.

Construction of Polylysine Dendrimer Nanocomposites Carrying Nattokinase and their Application in Thrombolysis

Thrombotic disease has become one of the leading causes of mortality among humans globally. Nattokinase (NK), a novel thrombolytic agent, has attracted the attention of researchers. However, NK is a serine protease that is vulnerable to environmental effects resulting in its inactivation. In this study, polylysine dendrimer (PLLD) was synthesized through divergence-convergence method, and a series of NK/PLLD nanocomposites with different molar ratio was prepared. In addition, NK was successfully incorporated into the cores of PLLD G4 through hydrogen bonds and van der Waals forces. In NK/PLLD nanocomposites, when the molar ratio of NK to PLLD is 1:30, a high relative enzyme activity level (up to 117%) was achieved and was more stable at different temperatures and pH than free NK. In in vitro thrombolysis experiment, compared with free NK, NK/PLLD nanocomposites could control the release of NK. The thrombolysis rate of NK/PLLD nanocomposites reached 50% at 12 h, which can effectively avoid other complications such as hemorrhage. Interestingly, NK/PLLD nanocomposites with positive charge can penetrate into the negatively charged thrombus through electrostatic interaction, thus providing a good thrombolytic effect. Hemolysis and MTT experiments show that PLLD nanomaterials can serve as ideal carriers of protein drugs.

Novel amphiphilic glucose-responsive modified starch micelles for insulin delivery

The high pKa (8.26 to 8.6) of PBA has restricted its glucose-responsiveness in physiological conditions, and the high cytotoxicity of polymers is also a limiting problem in their potential application for insulin delivery. Novel amphiphilic glucose-sensitive dialdehyde starch polymers containing 3-aminophenylboronic acid (APBA) as a glucose-responsive group and mPEGylated dialdehyde starch (mPEG-DAS) with hydrophobic 7-hydroxycoumarin-4-acetic acid (Cou) were synthesized. This dialdehyde starch derivative can self-assemble into mPEG-DAS–APBA–Cou micelles with “shell–core” structures in phosphate-buffered saline solution (PBS). In addition, the drug-loaded micelles can release insulin rapidly in response to hyperglycemia in a physiological environment. The results demonstrated that the mPEG-DAS–APBA–Cou micelles showed notable glucose responsive behavior near the physiological range. The insulin release from the nanocarriers is sensitive to different concentrations of glucose, releasing insulin rapidly under the conditions of 3 mg mL−1 glucose while demonstrating comparatively inert release at 1 mg mL−1 glucose (pH 7.4). MTT assays and hemolysis studies both confirmed that the mPEG-DAS–APBA–Cou micelles have low cytotoxic activity to A549 cells and low blood toxicity. These results suggest that the glucose-sensitive dialdehyde starch micelles (mPEG-DAS–APBA–Cou) have potential applications as a glucose-responsive material for insulin delivery.

Pluronic F127–chondroitin sulfate micelles prepared through a facile method for passive and active tumor targeting

Tumor-specific drug delivery is still a challenge in cancer therapy. Passive tumor targeting strategies, such as the enhanced permeability and retention (EPR) effect, cause nanocarriers to accumulate in tumors. However, this strategy can not provide specific tumor targeting. In this study, Pluronic F127 (PF127), a block copolymer which can inhibit drug efflux transporters in cancer therapy, was modified to form tumor-specific micelles with a natural polysaccharide, chondroitin sulfate (ChS), which imparts the site-specific property. A facile and efficient method based on Schiff base reaction was developed to facilitate both basic and clinical research. A series of PF127–ChS micelles with different ratios of PF127 and ChS were fabricated and evaluated in terms of size, morphology, drug loading efficiency and drug release behavior. Spherical micelles with a mean diameter of 155–241 nm were obtained. Their critical micelle concentration (CMC) was significantly reduced in contrast to PF127 micelles and their stability was enhanced. Doxorubicin (DOX) was loaded into the hydrophobic core of PF127 or adsorbed by ChS through electrostatic interactions with the negative charges of chondroitin sulfate. In vitro DOX release studies showed that DOX release from the micelles was enhanced at acidic pH values compared to physiological pH. A cytotoxicity assay (MTT) determined that the micelles possess significantly lower toxicity. Confocal microscopy and flow cytometry analysis indicated that DOX loaded micelles could efficiently release DOX inside cells by specific cellular uptake. These outcomes revealed that PF127–ChS micelles could be exploited as carriers for anti-tumor drugs for site-specific therapy of solid tumors.