Preparation and characterization of superparamagnetic chitosan microspheres: Application as a support for the immobilization of tyrosinase

Superparamagnetic chitosan microspheres were prepared by a water‐in‐oil suspension‐crosslinking technique. To this end, magnetite particles were dispersed in a chitosan solution in acetic acid. The dispersion was added to toluene containing Span 20 as a surfactant with stirring. Chitosan solution droplets were hardened with glutaraldehyde. The magnetic chitosan microspheres obtained were characterized with scanning electron microscopy, differential thermal analysis, and vibrational magnetometry. The microspheres had a wide size distribution, ranging from 43 ± 25 to 255 ± 55 μm, that depended on the reaction conditions. The mean particle size decreased with an increase in the concentration of Span 20 or the amount of glutaraldehyde and with the addition of NaCl. However, a major size reduction was achieved by an increase in the stirring rate. Tyrosinase was immobilized on the microspheres. The immobilized enzyme retained 70% of its activity, as determined by the capacity to degrade phenolic compounds. The immobilized tyrosinase resulted in greater stability than the free enzyme. In addition, the enzyme maintained 65% of its phenol oxidation activity after 10 cycles of reuse. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 98: 651–657, 2005     

Human serum albumin (HSA) adsorption with chitosan microspheres

In this study, chitosan microspheres were prepared and characterized for adsorption of human serum albumin (HSA) as affinity sorbent. The chitosan microspheres were obtained with a “suspension crosslinking technique” in the size range of 30–700 μm by using a crosslinker, i.e., glutaraldehyde. The chitosan microspheres used in HSA adsorption studies were having the average size of 170 ± 81 μm. Adsorption medium pH and the initial HSA concentration in the adsorption medium were changed as 4.0–7.0 and 0.5–2.0 mg HSA/mL, respectively, to investigate the HSA adsorption capacity of chitosan microspheres. Maximum HSA adsorption (i.e., 11.35 mg HSA/g chitosan microspheres) was obtained at pH 5.0 and 1.5 mg HSA/mL of the initial HSA concentration in the adsorption medium was obtained as the saturation value for HSA adsorption. A very common dye ligand, i.e., Cibacron Blue F3GA was attached to the chitosan microspheres to increase the HSA adsorption capacity. Actually, the HSA adsorption capacity was increased up to 15.35 mg HSA/g chitosan microspheres in the case of Cibacron Blue F3GA attached to chitosan microspheres used. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 86: 3035–3039, 2002     

Preparation,characterization, and salicylic acid release behavior of chitosan/poly(vinyl alcohol) blend microspheres

Blend microspheres of chitosan (CS) with poly(vinyl alcohol) (PVA) were prepared as candidates for oral delivery system. CS/PVA microspheres containing salicylic acid (SA), as a model drug, were obtained using the coacervation‐phase separation method, induced by addition of a nonsolvent (sodium hydroxide solution) and then crosslinked with glutaraldehyde (GA) as a crosslinking agent. The microspheres were characterized by Fourier transform infrared spectroscopy, differential scanning calorimetry (DSC), and scanning electron microscopy. Percentage entrapment efficiency, particle size, and equilibrium swelling degree of the microsphere formulations were determined. The results indicated that these parameters were changed by preparation conditions of the microspheres. Effects of variables such as CS/PVA ratio, pH, crosslinker concentration, and drug/polymer (d/p) ratio on the release of SA were studied at three different pH values (1.2, 6.8, and 7.4) at 37°C. It was observed that SA release from the microspheres increased with decreasing CS/PVA ratio and d/p ratio whereas it decreased with the increase in the extent of crosslinking. It may also be noted that drug release was much higher at pH 1.2 than that of at pH 6.8 and 7.4. The highest SA release percentage was obtained as 100% for the microspheres prepared with PVA/CS ratio of 1/2, d/p ratio of 1/2, exposure time to GA of 5 min, and concentration of GA 1.5% at the end of 6 h. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Synthesis and characterization of modified chitosan microspheres: Effect of the grafting ratio on the controlled release of nifedipine through microspheres

The grafting of acrylamide onto a chitosan backbone was carried out at three acrylamide concentrations (polymer/monomer ratio = 1:1, 1:2, and 1:3). The synthesis of the grafted polymer was achieved by K₂S₂O₈‐induced free‐radical polymerization. Microspheres of polyacrylamide‐g‐chitosan crosslinked with glutaraldehyde were prepared to encapsulate nifedipine (NFD), a calcium channel blocker and an antihypertensive drug. The microspheres of polyacrylamide‐g‐chitosan were produced by a water‐in‐oil emulsion technique with three different concentrations of glutaraldehyde as the crosslinking agent. Fourier transform infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC) were used to characterize the grafted copolymers, and the microspheres were prepared from them. FTIR and DSC were also used to analyze the extent of crosslinking. The microspheres were characterized by the particle size; the water transport into these microspheres, as well as the equilibrium water uptake, were studied. Scanning electron microscopy confirmed the spherical nature of the particles, which had a mean particle size of 450 μm. Individual particle dynamic swelling experiments suggested that with an increase in crosslinking, the transport became case II. The release of NFD depended on the crosslinking of the network and on the amount of drug loading. Calculating the drug diffusion coefficients with the initial time and later time approximation method further supported this. The drug release in all 27 formulations followed case II transport, and this suggested that the time dependence of the NFD release followed zero‐order kinetics. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 89: 2940–2949, 2003     

Chitosan,itaconic acid and poly(vinyl alcohol) hybrid polymer networks of high degree of swelling and good mechanical strength

Chitosan is a biodegradable, non‐toxic, biocompatible polymer convenient for use in drug delivery. In this study, hybrid polymeric networks (HPNs) based on chitosan, itaconic acid and poly(vinyl alcohol) (PVA) were prepared and characterized. Chitosan was dissolved in itaconic acid in order to obtain ionic crosslinking with the dicarboxylic acid. In the second step, this chitosan/itaconic acid network was mixed with PVA and chemically crosslinked with glutaraldehyde. The chitosan/itaconic acid ratio was kept constant, while the concentrations of PVA and glutaraldehyde were varied. All samples were characterized using swelling studies, dynamic mechanical analysis, Fourier transform infrared spectroscopy, differential scanning calorimetry, thermogravimetric analysis, X‐ray diffraction and scanning electron microscopy. The equilibrium degrees of swelling obtained for the HPNs were higher than most of the values reported for chitosan hydrogels obtained by dissolving chitosan in acetic acid or HCl aqueous solutions. This method of synthesis also resulted in hydrogels with better mechanical properties and thermal stability. By changing the PVA content and the degree of crosslinking, it is possible to finely tune the properties of the HPNs, which could make them suitable as potential matrices in controlled drug delivery. Copyright © 2010 Society of Chemical Industry     

壳聚糖/聚醚半互穿网络水凝胶的性能

以壳聚糖和聚醚为原料,戊二醛为交联剂,在醋酸溶液中制备了壳聚糖/聚醚水凝胶,反应温度45℃,聚醚和壳聚糖的质量比为0.4,戊二醛浓度为0.053 mol/L,壳聚糖黏均相对分子质量为24.86×104时,其凝胶饱和溶胀度为876.25%;反应温度45℃,聚醚和壳聚糖的质量比为0.6,戊二醛浓度为0.267 mol/L,壳聚糖黏均相对分子质量为24.86×104时,其凝胶硬度为151.896 kPa。     

Synthesis and characterization of injectable chitosan cryogel microsphere scaffolds

Treatment of tissue defects involves invasive processes such as implanting the tissue engineered scaffold to the defected area. Injectable scaffolds are increasingly being developed to achieve tissue regeneration in a less invasive manner. In this study, injectable chitosan cryogels in the form of microspheres were synthesized combining the water in oil emulsification method with the crosslinking of microspheres during cryogelation. The effects of polymer ratio, crosslinker concentration, cryogelation temperature, and stirring speed on the resulting cryogels’ chemistry, pore morphology, microsphere size, swelling ratio, degree of crosslinking, and degradation rate were examined for a possible noninvasive tissue engineering application. Microspheres with optimized properties were developed with an average pore and particle size of 5.50?±?0.63 and 220.11?±?25.58?µm at a chitosan ratio of 1%, glutaraldehyde concentration of 3%, reaction temperature of ?16°C, and stirring rate of 1,000?rpm.     

聚乙烯醇-壳聚糖复合水凝胶的溶胀性能

以聚乙烯醇(PVA)和壳聚糖为原料、以戊二醛为交联剂,在醋酸溶液中合成了聚乙烯醇-壳聚糖复合水凝胶,研究了影响水凝胶溶胀性能的多种因素,实验结果表明,该凝胶对pH、离子、温度敏感,且在pH=3.13盐酸溶液、常温下的蒸馏水及8℃蒸馏水中溶胀度较大,分别为1 112.2%、974.2%、1 036.8%,凝胶溶胀度随着干燥温度及干燥时间的增加而减小,聚乙烯醇种类对水凝胶溶胀性能有显著影响,PVA-1788与壳聚糖形成的水凝胶溶胀度最大为2 074.1%。聚乙烯醇-壳聚糖复合水凝胶因具有优良的机械强度、生物相容性及生物降解性,同时又具有pH/离子/温度敏感性,因此日益显示其在生物医学材料等领域的重要性。     

Synthesis and characterization of composite magnetic microspheres of artemisia seed gum and chitosan

In this study, composite magnetic microspheres of artemisia seed gum and chitosan were prepared in a well‐shaped spherical form with a size range of 230–460 μm by the suspension crosslinking technique for use in the application of magnetic carrier technology. The magnetic material used in the preparation of the composite microspheres was prepared by precipitation from FeCl₃ and FeSO₄ solution in basic medium. The morphological, magnetic properties, and the functional groups of the microspheres were characterized by different techniques (i.e., SEM, magnetometry, and FTIR). The results demonstrated that the stirring rate of the suspension and the Fe₃O₄/chitosan ratio are the most effective parameters for the average of the size distributions and the magnetic quality of the microspheres, while the amount of artemisia seed gum and Tween‐80 have no significant effect on these properties. The best magnetic quality of the composite magnetic microspheres is around 4.08 emu/g microspheres at 10 KG magnetic field intensity. The thermal stability of the composite magnetic microspheres was measured by using DSC methods. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 103: 3045–3049, 2007     

Crosslinking of Isabgol husk polysaccharides for microspheres development and its impact on particle size,swelling kinetics and thermal behavior

The microspheres were prepared by emulsification method using glutaraldehyde as crosslinker. The effects of variables as temperature, concentration of Isabgol husk and glutaraldehyde, and nature of dispersing media were analyzed on microsphere-derived properties such as size distribution, surface morphology, and swelling kinetics. The nature of crosslinking and interaction of polysaccharides structure with glutaraldehyde  were assessed by thermal analysis and infrared spectroscopy. The spherical and free flowing microspheres were obtained and a significant effect of process variables was observed on characteristics of formulations. The microspheres revealed their potential in the development of sustained release drug carriers for water soluble/insoluble drugs.     

Studies on Glutaraldehyde Crosslinked Chitosan Hydrogel Properties for Drug Delivery Systems

Chitosan was crosslinked with different amount of glutaraldehyde to prepare appropriate hydrogels to be used as drug delivery system. The swelling behavior of freeze-dried hydrogels in aqueous media at different temperature and pHs has been examined. The swelling, porosity and biocompatibility behavior of samples were investigated to check effects of polymer/polymer and polymer/drug interactions on these system characteristics. Obtained experimental results illustrates that with increasing crosslinking agent from 0.068 to 0.30, swelling of the prepared samples degrees from 1200% to 600% and pore diameters change from 100 to 500 µm. To investigate systems biocompatibility in gastric conditions, effects of crosslinker concentration on the pepsin enzyme activity have been studied using variation of relative viscosity of the system. Presented results also show that with increasing crosslinker agent concentration activity of enzyme reduces considerably and so crosslinker molar ratio to amine functional groups of chitosan must be less than 0.2.     

改性季铵化壳聚糖阴离子交换膜的制备与表征

以壳聚糖（CS）为原料,2,3-环氧丙基三甲基氯化铵（GTA）为醚化剂,通过亲核取代反应制备了季铵化壳聚糖（QCS）,用傅立叶变换红外光谱（FT-IR）表征了产物的结构,结果表明产物结构与目标产物的结构相符。以QCS为原料,醋酸溶液为溶剂,通过加入交联剂戊二醛（GA）和荷正电聚苯乙烯（PS）微球,制备了一系列改性QCS阴离子交换膜,并对其含水率、溶胀度、离子交换量等性能进行了测定。结果表明：交联剂的加入可有效抑制QCS膜的形变,降低了其溶胀度,微乳液的加入会在一定程度上提高复合膜的离子交换能力,交联度为4%、微乳液用量为15%（v/v）时离子交换膜的含水率趋于稳定。     

Preparation,characterization, and potential biomedical application of composite sponges based on collagen from silver carp skin

To reuse fish processing waste for biomedical materials, collagen (Col) was extracted from silver carp skin, and Col–chitosan (Ch) composite sponges were prepared by a freeze‐drying method. The atomic force microscopy and electrophoresis results suggest the Col might have been type I. To obtain the optimum conditions for the manufacture of the Col–Ch sponges, the characteristics of sponges composed of different ratios of Col to Ch with different crosslinkers were evaluated. Scanning electron microscopy showed that the sponges had an interconnected network structure with porosity. Infrared spectroscopy demonstrated that intermolecular crosslinkages between Col and Ch occurred. The swelling measurements implied that all of the sponges could bind an 18‐ to 36‐fold amount of distilled water and still maintain their form and stability. When the ratio of Col to Ch was higher than 1:0.25, the swelling and degradation rate decreased with increasing Ch. Cell proliferation, hemolysis, and hemostasis assay indicated that the sponges exhibited noncytotoxicity, biocompatibility, nonhemolysis, and hemostatic efficacy. Overall, we concluded that the optimal ratio of Col and Ch for the sponges was 1:0.25, and glutaraldehyde crosslinking was more suitable than 1‐ethyl‐3‐(3‐dimethylaminopropyl) carbodiimide hydrochloride. These results demonstrate the potential application of silver carp skin Col–Ch sponges for tissue engineering and wound dressing in non‐weight‐bearing tissue. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40998.     

Synthesis and characterization of polyacrylamide‐grafted chitosan hydrogel microspheres for the controlled release of indomethacin

Microspheres of polyacrylamide‐grafted‐chitosan crosslinked with glutaraldehyde were prepared and used to encapsulate indomethacin, a nonsteroidal anti‐inflammatory drug. The microspheres were produced by the water/oil emulsion technique and encapsulation of indomethacin was carried out before crosslinking of the matrix. The extent of crosslinking was analyzed by Fourier transform infrared spectroscopy and differential scanning calorimetry. Microspheres were characterized for drug‐entrapment efficiency, particle size, and water transport into the polymeric matrix as well as for drug‐release kinetics. Scanning electron microscopy confirmed the spherical nature and surface morphology of the particles with a mean particle size of 525 μm. Dynamic swelling experiments suggested that, with an increase in crosslinking, the transport mechanism changed from Fickian to non‐Fickian. The release of indomethacin depends upon the crosslinking of the network and also on the amount of drug loading. This was further supported by the calculation of drug‐diffusion coefficients using the initial time approximation. The drug release in all the formulations followed a non‐Fickian trend and the diffusion was relaxation‐controlled. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 87: 1525–1536, 2003     

一种新型壳聚糖分离介质的制备

以壳聚糖为载体、液体石蜡为分散介质、戊二醛为交联剂、Span80 为乳化剂,采用反相悬浮法制备壳聚糖微球,以环氧氯丙烷为活化剂、亚氨基二乙酸为螯合配基制备新型壳聚糖分离介质,并研究分离介质制备过程中各参数对壳聚糖分离介质性能的影响。确定最佳活化工艺为：40% DMSO/NaOH（0.6 mol/L）、ECH体积分数10%、反应温度40 ℃、反应时间4 h,测得环氧基修饰密度可达到0.15 mmol/g（gel）;最佳螯合工艺：IDA（0.6 mol/L）/ NaOH（2.0 mol/L）混合液,反应时间为6 h,制备的新型壳聚糖分离介质对Cu²⁺吸附量达到172.787 g/g gel,壳聚糖分离介质含水率为45.60%,孔隙率为69.45% ,得到一种新型金属螯合层析填料。     

生物粘附性微球的制备及其评价-I. 离子交联法制备生物粘附性微球及其粒径预测

以硫酸为离子交联剂,制备了几丁聚糖生物粘附性微球. 与硫酸盐作为离子交联剂相比,本方法制备的微球交联程度高,呈较规则的球形,表面致密,机械强度高,在人工模拟肠液中可以保存24 h以上. 微球的粒径是影响药物释放动力学的重要因素. 运用四因素二次正交回归组合设计方法考察了几丁聚糖浓度、交联剂浓度、交联时间和转速对微球粒径的影响,得出了制备几丁聚糖微球粒径的回归模型方程. 统计检验表明,其中几丁聚糖浓度和搅拌转速对微球粒径的影响最为显著.     

Ce(Ⅳ)盐引发丙烯腈在交联聚乙烯醇微球表面的接枝聚合

以戊二醛为交联剂,在反相悬浮体系中采用直接交联反应成球的方法,制备了聚乙烯醇(PVA)。以硫酸铈铵为引发剂,在酸性溶液聚合体系中实施了丙烯腈(AN)在交联微球CPVA表面的接枝聚合,制备了接枝微粒CPVA-g-PAN,考察了主要因素对交联成球反应与接枝聚合的影响规律。实验结果表明,在一定的搅拌速度下,分散剂用量及油水两相比是影响交联微球CPVA的主要因素。在Ce(Ⅳ)盐的氧化作用下,在含有大量羟基的CPVA微球表面会产生自由基,顺利地实现丙烯腈的自由基接枝聚合反应。反应温度、铈盐浓度和H+离子浓度是影响接枝聚合反应的主要因素。在适宜条件下,可制得PAN接枝度为27 g/100 g的接枝微球CPVA-g-PAN。     

T型微通道装置制备尺寸均一壳聚糖微球

采用T型微通道装置制备尺寸均一的壳聚糖微球. 研究了乳化剂用量、油水两相流速比和流速等条件对乳液粒径的影响,尝试制备了不同分子量的壳聚糖乳液,并确定了交联固化方式. T型微通道装置的油相通道直径350 mm,水相通道直径65 mm,两通道接口处直径16 mm. 以1.5%(w)的壳聚糖醋酸水溶液为水相,以液体石蜡/石油醚(7/5, j)的混合物作为油相,水相流速20 mL/min,油水两相流速比为15:1,4%(w)的PO-500作为油相乳化剂,制备得到的壳聚糖乳液粒径分布系数<10%. 以戊二醛的甲苯溶液作为交联剂,当戊二醛所含醛基与壳聚糖所含氨基的摩尔比为1:1时,交联时间选择2 h.     

Preparation of surface‐modified,micrometer‐sized carboxymethyl chitosan drug‐loaded microspheres

Drug‐loaded microspheres have attracted much attention in embolization therapy for liver cancer in recent years. Carboxymethyl chitosan has obvious advantages for biomedical applications because of its exceptional biocompatibility and biodegradability. In this study, surface‐modified carboxymethyl chitosan microspheres were prepared by the crosslinking reactions of carboxymethyl chitosan in a reverse suspension system with poly(ethylene glycol diglycidyl ether) (PEGDE) as the crosslinking agent; this was followed by the grafting polymerization of 2‐acrylamido‐2‐methyl propane sulfonic acid on the surface of the microspheres. The microspheres showed regular spherical shapes with size distributions ranging from 300 to 600 μm. Ion‐exchange groups (? COOH, ? SO₃H) were introduced into the microspheres; these groups could load doxorubicin with a loading rate as high as 34.6% in 24 h. This was an increase of 49.8% compared to that of the pure carboxymethyl chitosan microspheres. Additionally, the microspheres possessed large network structures because macromolecular PEGDE was used as the crosslinking agent. The drug‐release profile showed that the surface‐modified microspheres displayed a sustained‐release manner compared with the nonmodified microspheres in phosphate‐buffered saline. These microspheres have promising applications as drug‐loaded arterial embolization agents for the interventional treatment of tumors. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 45731.     

戊二醛对壳聚糖-聚醚水凝胶溶胀动力学的影响

以壳聚糖和聚醚为原料、戊二醛为交联剂合成了壳聚糖-聚醚水凝胶。研究了壳聚糖-聚醚水凝胶溶胀机理,探讨了戊二醛浓度对该水凝胶的溶胀度、溶胀速率和溶胀动力学的影响。结果表明,戊二醛浓度不仅是影响水凝胶溶胀度的主要因素,随着戊二醛浓度的增大,壳聚糖-聚醚水凝胶的溶胀度逐渐减小,而且影响其溶胀动力学类型,当戊二醛浓度为0.107 mol·L^-1,该水凝胶的溶胀过程属于Fickian类型,当戊二醛浓度为0.320、0.533 mol·L^-1,其溶胀过程属于non-Fickian类型。