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     

改性磁性壳聚糖微球的制备、表征及性能研究

以(NH4)2Fe(SO4)2.6H2O、NH4Fe(SO4)2.12H2O和壳聚糖为原料,经羟丙基化、胺基化,采用一步包埋法制备了一种新型的多胺基化磁性壳聚糖微球。通过正交实验法确定了磁性微球的最佳制备条件,即搅拌速度1200r/min,壳聚糖用量3.0g,环氧氯丙烷用量2.5mL,乙二胺用量2.5mL。并用IR、TG、XRD和SEM对其结构及形貌进行了表征。结果表明,Fe3O4磁性粒子已包埋了一层胺基化壳聚糖。磁性微球胺基含量为2.302mmol/g;呈较规则的球形,平均粒径为209nm,且具有顺磁性和良好的耐酸性。     

Magnetic chitosan microspheres: preparation and characterization

In this study, magnetic chitosan microspheres were prepared in a well shaped spherical form with a size range of 100 to 250 μm (size distribution ±15 to ±40 μm, respectively) by the suspension cross-linking technique for use in the application of magnetic carrier technology. The magnetic material (i.e. Fe₃O₄) used in the preparation of the magnetic chitosan microspheres was prepared by precipitation from FeSO₄ and Fe₂(SO₄)₃ solutions in basic medium and then ground to the desired size (i.e. 1–5 μm). The morphological and magnetic properties of the microspheres were characterized by different techniques (i.e. SEM, optical microscopy, magnetometry). The results demonstrated that the stirring rate of the suspension medium and the Fe₃O₄/chitosan ratio are the most effective parameters for the size/size distribution and the magnetic quality of the microspheres, while the chitosan molecular weight (MW) has no significant effect on these properties for the given MW range (i.e. 150 to 650 kDa). The best magnetic quality of the magnetic chitosan microspheres is around 9.1 emu/g microsphere at 10 kG magnetic field intensity.     

聚合物载药微球活性组分控释性能的动力学模拟

将聚合物载药微球的溶解扩散模型与药代动力学模型相结合,计算了载药微球的药物控释性能的浓度时间曲线.采用叠加法计算了多次投药所产生的稳态药物浓度特征,探讨了释放速率、给药时间间隔对药物浓度曲线的影响.相对于口服药物溶液,微球中的药物通过载体的控制释放,血药浓度峰值有很大的降低,多次给药时载药微球的药物浓度波动也有大幅度的减小;适当的溶解速率可减小药物浓度波动,同时也满足治疗所要求的浓度值.     

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     

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     

Effect of coexcipients on drug release and floating property of nifedipine hollow microspheres: A novel gastro retentive drug delivery system

A gastro retentive drug‐delivery system for nifedipine was developed by incorporating the drug in cellulose acetate hollow microspheres capable of floating on the gastric and intestinal fluid. The microspheres were prepared by solvent diffusion–evaporation technique in the presence of coexcipients like polyethylene glycol, dibutyl phthalate, and poly(ε‐caprolactone) using ethyl acetate as a dispersing solvent. Size of the microparticles depends upon the type and concentration of the excipient used. Microparticles exhibited floating properties on the simulated‐gastric fluid for >12 h. Their percentage buoyancy followed the rank order of: blank (no coexcipients) > dibutyl phthalate > polyethylene glycol > poly(ε‐caprolactone) after 15 h of floating. Release of nifedepine was enhanced by the addition of coexcipients. The drug release followed non‐Fickian transport in almost all formulations. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 100: 486–494, 2006     

水溶性壳聚糖及磁性壳聚糖微球的制备

以废弃蟹壳为原料制备出了高脱乙酰度壳聚糖和脱乙酰度50%的水溶性壳聚糖,通过电位滴定、红外光谱等对产物的脱乙酰度、功能基团作了表征,测定了产物的黏度,结果表明制备的水溶性壳聚糖的动力黏度为82.9 mPa.s。以0.01 mol/L硝酸钴和0.02 mol/L硝酸铁的混合溶液,采用微乳液法制备了纳米铁酸钴,以水溶性壳聚糖为原料制备了壳聚糖/纳米铁酸钴复合微球,TEM结果显示该磁性壳聚糖微球为规则球形,粒径13μm左右,分散性好。     

Synthesis and characterization of methoxypolyethyleneglycol and lauric acid grafted novel polyurethanes for controlled release of nifedipine

Novel polyurethanes (PUs) grafted with methoxypolyethyleneglycol (mPEG) and lauric acid (LA) were synthesized by solution polymerization using dibutyl tin dilaurate as a catalyst, taking different molar ratios of LA‐trimethylol propane (LA‐TMP) with respect to mPEG‐trimethylol propane (mPEG‐TMP). The polymers obtained were characterized by Fourier transform infrared spectroscopy and gel permeation chromatography to confirm, respectively, the PU formation and molecular weight. Moderate molecular‐weight PUs were obtained, and nifedipine (NFD)‐loaded microspheres were prepared by solvent evaporation method. The size of the microspheres as measured by laser light scattering technique ranged between 10 and 50 μm. An increase in the size of particles was observed with an increasing molar ratio of mPEG‐TMP with respect to LA‐TMP. The % encapsulation efficiency was found to vary between 65 and 92. The surface morphology of microspheres as studied by scanning electron microscopy revealed the spherical nature of the particles with wrinkles on their surfaces. Crystalline nature of the drug in the microspheres after loading was studied by X‐ray diffraction technique. The release of NFD through the matrix microspheres was investigated in pH‐7.4 phosphate buffer. An increase in release rate was observed with increasing molar ratio of mPEG‐TMP with respect to LA‐TMP. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 2007     

磁性壳聚糖微球的合成及其在固定化血管紧张素转化酶的应用

以化学共沉淀法合成Fe3O4纳米粒子为磁核,采用乳化交联法制备磁性壳聚糖微球,并对其形貌、结构和磁饱和强度等性质进行了表征。以磁性壳聚糖微球作为载体,固定化猪肺粗提物中的血管紧张素转化酶,并对固定化条件进行研究。结果表明,固定化血管紧张素转化酶的最佳条件为：pH值为8.3,最佳温度为50 ℃,最佳时间为1.5 h,最佳酶溶液蛋白浓度为6 mg/mL,此时固定化酶活力最高为0.048 U/g微球。与游离酶相比,固定化酶的pH值稳定性和热稳定性均得到提高。固定化酶重复使用10次,仍然保持40%以上相对活力,说明磁性壳聚糖微球是固定化血管紧张素转化酶的良好载体。     

Chitosan microspheres and sponges: Preparation and characterization

In this study, chitosan microspheres and sponges were prepared and characterized for diverse biomedical applications successfully. The chitosan microspheres were obtained with a “suspension crosslinking technique” in the size range of 30–700 μm. The stirring rate of the suspension medium and the chitosan/acetic acid ratio, emulsifier, and crosslinker, that is, the glutaraldehyde concentration in the suspension medium, were evaluated as the effective parameters on the size/size distributions of the microspheres. The microsphere size/size distributions were increased with the decreasing of all effective parameters except the chitosan/acetic acid ratio. In the second part of the study, chitosan sponges were prepared with a solvent‐evaporation technique and sponges were cross‐linked either during the formation or after the formation of sponges by using a cross‐linker, that is, glutaraldehyde. When the sponges were crosslinked during the formation, fibrillar structures were obtained, while the leaflet structures were obtained in the case of crosslinking after the formation of sponges. In the last part of the study, the swelling behavior of both the chitosan microspheres and sponges were evaluated using different amounts of the crosslinker. The swelling ratio was increased in both types of structures, that is, microspheres and sponges, by decreasing the amount of the crosslinker. © 2000 John Wiley & Sons, Inc. J Appl Polym Sci 76: 1637–1643, 2000     

Preparation and release behavior of carboxymethylated chitosan/alginate microspheres encapsulating bovine serum albumin

Microspheres were prepared from carboxymethylated chitosan (CM‐chitosan) and alginate by emulsion phase separation. Their structure and morphology were characterized with IR spectroscopy and scanning electron microscopy. Bovine serum albumin (BSA) was encapsulated in the microspheres to test the release behavior. The swelling behavior, encapsulation efficiency, and release behavior of BSA from the microspheres at different pHs and with a pH‐gradient condition were investigated. The BSA encapsulation efficiency was calculated to be 80%. The degree of swelling of the microspheres without BSA loaded at pH 7.2 was much higher than that at pH 1.0. The encapsulated BSA was quickly released in a Tris–HCl buffer (pH 7.2), whereas a small amount of BSA was released under acid conditions (pH 1.0) because of the strong electrostatic interaction between ? NH₂ groups of CM‐chitosan and ? COOH groups of alginic acid and a dense structure caused by a Ca²⁺ crosslinked bridge. For the simulation of the processing of the drug under the conditions of the intestine, the microspheres were tested in a pH‐gradient medium, in which an acceleration of the release occurred at pH 7.4 after a lag time at a low pH (5.8–6.8). At pH 7.4, a large amount of BSA was released from the microspheres in a short time because of the rapid swelling of the microspheres. However, the release only depended on the diffusion of BSA at relatively low pHs, this resulted in a relatively low release. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 92: 878–882, 2004     

Cu(Ⅱ)螯合壳聚糖磁性微球的制备、表征及性能研究

以(NH4)2Fe(SO4)2.6H2O、NH4Fe(SO4)2.12H2O和壳聚糖为原料,经羟丙基化、Cu(Ⅱ)螯合,采用一步包埋法制备了一种Cu(Ⅱ)螯合壳聚糖磁性微球。通过正交实验法确定了磁性微球的最佳制备条件,即搅拌速度1 200 r/min,壳聚糖用量3.0 g,环氧氯丙烷用量1.0 mL,CuCl2.2H2O为0.010 mol。并用IR、TG、XRD和SEM对其结构及形貌进行了表征,结果表明,Fe3O4磁性粒子已包埋了一层Cu(Ⅱ)螯合壳聚糖,呈较规则的球形,平均粒径为240 nm,且具有顺磁性。     

壳聚糖希夫碱及壳聚糖改性微球的吸附性能研究

以壳聚糖和对二甲氨基苯甲醛为原料合成壳聚糖希夫碱,以壳聚糖希夫碱为底物,采用反相悬浮聚合法,制备壳聚糖希夫碱微球。对二者的吸附性能进行比较研究。结果表明,希夫碱微球的吸附性能优于壳聚糖希夫碱,对四氧化三铁的吸附容量分别为113.179 mg/g和39.279 mg/g,对亚甲基蓝的吸附平衡时间均为150 min,饱和吸附容量随着亚甲基蓝初始质量浓度的增大而增大,且微球的吸附容量大于壳聚糖希夫碱,吸附率不随浓度增大单调递增,而是有一极大值。     

Synthesis and characterization of chitosan/cloisite 30B film for controlled release of ofloxacin

In this research program, chitosan film was prepared by blending chitosan with Cloisite 30 B at different concentrations 0 wt %, 1 wt %, and 2.5 wt %. The blends were characterized by Fourier transmission infrared spectroscopy (FTIR), scanning electron microscopy (SEM), X‐ray diffraction (XRD) analysis. From the FTIR spectra the various groups present in chitosan/C 30 B blend were monitored. The homogeneity, morphology, and crystallinity of the blends were ascertained from SEM and XRD data, respectively. The most suitable form of blend was taken and used as a carrier for the controlled release of ofloxacin. The swelling studies have been carried out at different drug loading. Drug release kinetics was analyzed by plotting the cumulative release data versus time by fitting to an exponential equation which indicated the occurrence of non‐Fickian type of kinetics. The drug release was investigated at different pH medium and it was found that the drug release depends upon the pH medium as well as the nature of matrix. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012     

聚乳酸硝苯地平缓释微球的制备与释药性能研究

以熔融缩聚制得的聚乳酸（PLA）作为载体,以聚乙烯醇为分散剂,二氯甲烷为溶剂,采用乳化-溶剂蒸发法制备聚乳酸硝苯地平（PLA／NFD）缓释微球。通过红外光谱（FT—IR）和生物显微镜对聚乳酸硝苯地平缓释微球进行了表征,并用紫外分光光度法探讨了聚乳酸硝苯地平缓释微球的释药性能。结果表明：聚乳酸硝苯地平缓释微球呈现以光滑完整的球形,且聚乳酸和硝苯地平药物能够有机地结合为一体。合成的聚乳酸硝苯地平球形微球具有明显的缓释作用,而且增大硝苯地平,聚乳酸投药比,会提高微球的释放度,但包封率下降。     

N-mPEG-O-季铵化壳聚糖微球的制备及其载药性能

将聚乙二醇单甲醚（mPEG）醛化改性后,通过西佛碱反应接枝到自制的O-季铵化壳聚糖的NH2上,硼氢化钠还原制得N-mPEG接枝O-季铵化壳聚糖（QACS-mPEG）,反相悬浮法制备二乙烯基砜交联QACS-mPEG微球。用FTIR、1 H NMR、EA和SEM对产物进行表征,并且以酮洛芬为模型药物研究微球的载药性能及释放行为。结果表明,mPEG和季铵盐基团的引入提高了N-mPEG-O-季铵化壳聚糖微球的载药量,为4.31mg/mg;载药N-mPEG-O-季铵化壳聚糖微球在模拟肠液的缓释效果优于胃液,微球释药具有pH响应性。     

壳聚糖改性疏水缔合聚丙烯酰胺的制备及表征

为了改善疏水缔合聚丙烯酰胺的溶解性以及溶液稳定性,本文采用巯基壳聚糖对疏水缔合聚丙烯酰胺进行改性,红外表征结果说明巯基壳聚糖连接到了聚丙烯酰胺分子链上。对影响壳聚糖改性实验的因素进行分析,实验结果说明,壳聚糖中巯基含量增大、壳聚糖加入量增大以及改性反应温度升高都会造成聚合物分子量降低,当改性反应的反应温度不高于35℃、添加壳聚糖质量不高于单体质量的3%时,得到的改性聚合物分子量满足现场使用要求。对改性聚合物的溶解性及溶液稳定性进行了评价,结果表明,壳聚糖中巯基含量增大及壳聚糖加入量增大对聚合物溶解性及溶液稳定性有明显的改善,聚合物的溶解时间由改性前的150min最多缩短至20min,聚合物溶液黏度保留率由改性前的60%最多提高到90%以上,壳聚糖改性有望弥补疏水缔合聚合物现场使用中的一些不足。     

壳聚糖接枝聚丙烯酰胺水凝胶的制备及性质研究

通过接枝共聚反应制备了几种壳聚糖接枝聚丙烯酰胺水凝胶，其中过硫酸钾为自由基引发剂，亚甲基双丙烯酰胺或甲醛为交联剂，并研究了实验因素，如交联剂浓度和单体比率对水凝胶溶胀能力的影响。实验表明水凝胶具有离子强度、pH值和温度敏感性。这种可随外界因素响应及“开关”的性质，使此类智能水凝胶有望成为生物制品载体，例如药物载体。     

Effect of proteolytic enzymes in gastrointestinal fluids on drug release from polyelectrolyte complex microspheres based on partially phosphorylated chitosan

This study investigated the effect of proteolytic enzymes on in vitro release of ibuprofen from phosphorylated chitosan (PCS) microspheres in simulated gastric fluid (SGF) (pH 1.4) and simulated intestinal fluid (SIF) (pH 7.4). To reduce the enzymatic degradability and to enhance the sustained release property, polyelectrolyte complex microspheres based on PCS were developed and characterized. The ibuprofen release from PCS microspheres was found to be sustained more effectively than that from CS microspheres in the medium containing proteolytic enzymes. It was concluded that the PCS microspheres can be used more successfully as sustained oral drug‐delivery vehicles than CS microspheres due to their lesser enzymatic degradability. Copyright © 2004 Society of Chemical Industry