离子凝胶法制备壳聚糖纳米微粒

采用离子凝胶法,以不同浓度壳聚糖溶液与多聚磷酸盐(TPP)溶液配比反应制备壳聚糖纳米微粒,观察了壳聚糖、多聚磷酸盐浓度、壳聚糖与多聚磷酸盐的质量比和反应体系pH值对纳米微粒制备的影响。在壳聚糖与多聚磷酸盐溶液浓度分别为0.6~3.0 mg/mL与0.5~1.5 mg/mL时,保持质量比在3∶1~6∶1之间,可稳定得到壳聚糖纳米微粒;当pH值为5.0~6.0时壳聚糖纳米微粒保持稳定,当pH>7.0则出现沉淀。     

一种新型的负载蛋白质药物微球的制备和释药性能

为了制备具有蛋白药物结肠靶向释放性能的新型药物载体,采用了水相溶液滴定反应法,分别以牛血清白蛋白(BSA)和乳铁蛋白(LF)为模型蛋白质药物,制得壳聚糖/纤维素磷酸钠(NaCS)/三聚磷酸钠(TPP)载药微球。利用电镜SEM和显微镜观测拍照,对微球的表面和截面形貌进行了表征,发现微球球形规则且颗粒大小均一。同时进行了体外药物模拟释放试验,考察了载药微球先后经过模拟胃液、模拟小肠液和模拟结肠液时的释药性能,及不同的释放条件和制造条件对于微球释药性能的影响,尤其考察了不同蛋白药物和不同干燥方式的影响。结果表明由临界点干燥法制得的负载乳铁蛋白(LF)微球在模拟胃液和小肠液释放量中5 h内只释放出不到20%的蛋白药物,而后在结肠模拟液中4 h内释放出蛋白药物80%以上。这些结果表明,壳聚糖/NaCS/TPP体系具有一定的作为结肠靶向药物释放载体的应用潜力。     

亚微米级高洁净度聚倍半硅氧烷微球的制备

在去离子水溶液中以甲基三甲氧基硅烷作为反应单体,通过水解-缩聚两步法合成了亚微米级聚倍半硅氧烷微球。考察了去离子水的电导率和单体pH值对水解反应时间、聚合成球时间和微球粒径的影响,以及单体氯离子含量对微球表面洁净度的影响。通过扫描电子显微镜、粒度分布测试、傅里叶变换红外光谱及热重分析对所制备微球的形貌、粒径分布、有机功能基及热性能进行了分析表征。结果表明,在去离子水电导率小于15μS/cm、单体pH值为4～5以及单体氯离子含量小于0.023 mg/L的条件下,有利于制得亚微米级的高洁净度聚倍半硅氧烷微球。     

水解CaCO_3作为交联剂制备羧甲基壳聚糖凝胶微球

羧甲基壳聚糖水溶液在一定转速下分散在石蜡油中可形成油包水结构,通过加入碳酸钙体系的交联剂可形成不溶于水的交联微球,将微球分离干燥得到羧甲基壳聚糖的交联粉末,可作为止血粉使用。分别使用GDL/碳酸钙和柠檬酸/碳酸钙复合体系制备羧甲基壳聚糖凝胶微球,其中,柠檬酸可在水热环境下原位还原硝酸银,一步法直接制备含银羧甲基壳聚糖微。结果表明,GDL/碳酸钙和柠檬酸/碳酸钙均可形成微米级的羧甲基壳聚糖凝胶微球。使用柠檬酸/碳酸钙可制备含银的羧甲基壳聚糖凝胶微球,纳米银的紫外吸收峰出现在445 nm处,为纳米级。     

两相溶胶－凝胶法制备微米二氧化硅

采用两相溶胶-凝胶法,以正硅酸乙酯、氨水、乙醇、水、微量电解质为原料,制备出微米级单分散性二氧化硅微球,着重研究了微量电解质加入量、加料时间、加料方式、不同溶剂配比对二氧化硅微球粒径的影响.结果表明,二氧化硅微球粒径随着电解质浓度的增大先减小后增大;随着加料时间的延长,二氧化硅微球粒径逐渐增大;连续加料比间歇加料制得的二氧化硅微球单分散性好;溶剂类型对二氧化硅微球粒径有很大影响,通过不同溶剂配比调控二氧化硅微球粒径,最终制备出单分散性好的微米二氧化硅微球.     

层层自组装载盐酸小檗碱微球的制备及释药性研究

采用离子交联法制备载盐酸小檗碱的海藻酸钙/壳聚糖盐酸盐(ALG-Ca/CHI)模板微球,利用层层自组装技术将羧甲基纤维素钠(CMC)和CHI逐层络合制得载盐酸小檗碱微球。通过CLSM、FT-IR、SEM、溶胀实验和体外释药实验对载药微球的性能进行研究,结果表明,CMC与CHI通过静电作用形成聚电解质复合物成功包覆在ALG-Ca凝胶表面,微球剖面边缘出现层层膜结构且膜层总厚度约为20.26μm,载盐酸小檗碱ALG-Ca/(CHI/CMC)3微球释药发现,在37℃,pH越高,累计释放率越高。     

α-酮戊二酸修饰壳聚糖微球对牛血清蛋白的吸附

采用反相悬浮法制备交联壳聚糖微球,再与α-酮戊二酸反应生成Schiff碱,NaBH4还原制得改性壳聚糖微球.用FFIR、SEM和XRD对其进行表征,并将之用于牛血清白蛋白的吸附研究,考察了吸附时间,溶液pH值、牛血清白蛋白的浓度.温度、NaCl含量等因素对牛血清白蛋白吸附的影响.结果表明,α-酮戊二酸改性交联壳聚糖微球不溶于酸和碱,对牛血清白蛋白具有良好的吸附性能,在pH=5.0时,吸附在1 h内可达平衡,吸附数据符合Langmuir等温方程和Lagergren二级动力学方程.     

壳聚糖固载环糊精微球的制备及吸附硝基酚

反相悬浮法制备甲醛保护壳聚糖(CTS)微球,环氧氯丙烷为交联剂β-环糊精反应制得壳聚糖固载环糊精微球。产物用红外光谱、扫描电子显微镜和X射线衍射仪进行表征,并用于吸附2,4-二硝基酚研究。考察了吸附时间、溶液pH值、酚浓度和NaCl含量对吸附的影响。实验结果表明,壳聚糖固载环糊精(CTS-CD)微球具有较好的耐酸碱性能,在pH值为3.6条件下,对2,4-二硝基酚的吸附快速达到平衡,吸附量为325mg/g,吸附符合Freundlich等温方程和二级动力学方程。     

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。     

单分散聚甲基丙烯酸甲酯微球的制备

选择分散聚合方法制备微米级单分散聚甲基丙烯酸甲酯微球,改变反应物间的配比及反应条件,考察了引发剂浓度、稳定剂浓度对微球粒径的影响及变化规律,同时对微米级单分散聚甲基丙烯酸甲酯微球提出最佳的制备方案.     

水溶性壳聚糖纳米粒子的制备及其BSA载药性能

为了避免高分子量壳聚糖水溶性差以及增溶剂乙酸可能带来的负面作用,本文选择低分子量水溶性壳聚糖 (WSC)作研究对象,采用三聚磷酸(TPP)作交链剂制备不同WSC/TPP比率的WSC纳米粒子,并用于牛血清白蛋白 (BSA)的释放载体。经测得为球形形貌的纳米粒子空载和载药时粒径、Zeta电位分别在35～190 nm、35～42 mV。红外光谱及X–射线衍射证实了纳米粒子中WSC的氨基与TPP的磷酸基团发生了交联反应。纳米粒子载药性能试验表明在0.05～1 mg/mL范围内随着BSA浓度的增大,纳米粒子的载药量增加而负载率降低。体外释放实验表明水溶性壳聚糖纳米载体对蛋白质药物具有缓释特征。因此,水溶性壳聚糖有望成为新的载体应用于蛋白质药物的控制释放。     

Preparation of nanoparticles composed of chitosan and its derivatives as delivery systems for macromolecules

Three different kinds of nanoparticles for paracellular transport were prepared using a simple and mild ionic‐gelation method. Sodium tripolyphosphate (TPP) as crosslinking agent was added into three kinds of solutions, which were chitosan solution, physical blending solution of chitosan, and glycidyl trimethylammonium chloride (GTMAC), and O‐(2‐hydroxyl) propyl‐3‐trimethyl ammonium chitosan chloride (O‐HTCC) solution respectively. O‐HTCC was synthesized by coupling of GTMAC to chitosan whose functional groups of the NH₂ groups were protected. The nanoparticles were characterized by transmission electron microscopy, atomic force microscopy, photon correlation spectroscopy, and zeta potential measurement. The results showed that increasing TPP concentration promoted the size of chitosan nanoparticles, a decrease in the size of O‐HTCC nanoparticles incurred on the contrary. The size of O‐HTCC nanoparticles is slightly bigger than that of pure chitosan nanoparticles, and smaller than that of physical blending nanoparticles (PBN). Bovine serum albumin (BSA), as a model protein drug, was incorporated into the nanoparticles. Compared with chitosan nanoparticles and PBN, high BSA loading efficiency (87.5%) and loading capacity (99.5%) are achieved by quaternized chitosan (O‐HTCC) nanoparticles, and the release profile of BSA from nanoparticles has an obvious burst effect and a slowly continuous release phase followed. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 2007     

Characterization of novel quaternary chitosan derivative nanoparticles loaded with protein

The objective of this work was to characterize a novel quaternary chitosan derivative [O‐(2‐hydroxyl) propyl‐3‐trimethyl ammonium chitosan chloride (O‐HTCC)] nanoparticle system. O‐HTCC nanoparticles were prepared with a simple and mild ionic gelation method upon the addition of a sodium tripolyphosphate solution to a low‐molecular‐weight O‐HTCC solution. Highly cationic chitosan nanoparticles were prepared. Bovine serum albumin (BSA), a model protein drug, was incorporated into the nanoparticles. The physicochemical properties of the nanoparticles were determined with transmission electron microscopy (TEM), scanning electron microscopy (SEM), Fourier transform infrared analysis, differential scanning calorimetry, and X‐ray diffraction (XRD) patterns. The results showed that increasing the BSA concentration from 1.5 to 2.5 mg/mL promoted the BSA encapsulation efficiency from 57.3% to 87.5% and the loading capacity from 70.2% to 99.5%. Compared with the chitosan nanoparticles, the O‐HTCC nanoparticles had lower burst release. TEM revealed that the BSA‐loaded O‐HTCC nanoparticles were smaller than the O‐HTCC nanoparticles when the BSA concentration was 1.5 mg/mL; SEM showed that the size of the BSA‐loaded O‐HTCC nanoparticles was mostly affected by the BSA concentration, and the increase in size occurred with the concentration increasing. Thermograms and XRD of the BSA‐loaded nanoparticles suggested that polyelectrolyte–protein interactions increased with the BSA concentration increasing and greater chain realignment in the BSA‐loaded nanoparticles. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

壳聚糖修饰磁性纳米粒子对BSA的吸附性能

采用化学共沉淀法制备磁性Fe3O4纳米粒子,以（3-氯丙基）三甲氧基硅烷为偶联剂将壳聚糖共价键合到磁性Fe3O4纳米粒子的表面,通过红外光谱（FTIR）、X射线衍射（XRD）、扫描电子显微镜（SEM）及热重分析（TGA）对其进行了表征。主要研究了不同影响因素（吸附时间、pH值、牛血清白蛋白浓度）下壳聚糖修饰的磁性纳米粒子对牛血清白蛋白（BSA）的吸附性能。结果得到壳聚糖修饰的磁性Fe3O4纳米粒子粒径为20 nm左右,壳聚糖在磁性Fe3O4纳米粒子表面的接枝率为15.40%。研究表明：在不同条件下,与未修饰的磁性Fe3O4纳米粒子相比,经壳聚糖修饰的Fe3O4纳米粒子对BSA均表现出较强的吸附能力。     

Controlled release of protein from magnetite–chitosan nanoparticles exposed to an alternating magnetic field

In this research, the controlled release of proteins from magnetite (Fe₃O₄)–chitosan (CS) nanoparticles exposed to an alternating magnetic field is reported. Fe₃O₄–CS nanoparticles were synthesized with sodium tripolyphosphate (TPP) molecules as a crosslinking reagent. Bovine serum albumin (BSA) was used as a model protein, and its controlled release studied through the variation of the frequency of an alternating magnetic field. The results show the successful coating of CS and BSA on the Fe₃O₄ nanoparticles with an average diameter of 50 nm. Intermolecular interactions of TPP with CS and BSA were confirmed by Fourier transform infrared spectroscopy. The application of low‐frequency alternating magnetic fields to such magnetic CS nanoparticles enhanced the protein release properties, in which the external magnetic fields could switch on the unloading of these nanoparticles. We concluded that enhanced BSA release from nanoparticles exposed to an alternating magnetic field is a promising method for achieving both the targeted delivery and controlled release of proteins. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 43335.     

The interaction between bovine serum albumin and the self-aggregated nanoparticles of cholesterol-modified O-carboxymethyl chitosan

The interaction between bovine serum albumin (BSA) and self-aggregated nanoparticles of cholesterol-modified O-carboxymethyl chitosan (CCMC) with different degrees of substitution (DS) of cholesterol moiety was studied by transmission electron microscopy (TEM), fluorescence quenching method and circular dichroism (CD) measurement. This interaction was started at the disaggregation of CCMC self-aggregated nanoparticles and reached equilibrium after 3-4 h. The apparent quenching constant (K_q) between BSA and CCMC self-aggregated nanoparticles calculated by the modified Stern-Volmer plot increased from 4.14 × 10⁴ to 1.95 × 10⁵ M⁻¹ with DS of cholesterol moiety increasing from 3.2% to 9.8%, whereas the fraction of tryptophan residues in BSA molecule involved in the interaction decreased at the same time. Compared with free BSA, the relative α-helix content of BSA decreased and the unfolding of BSA by a denaturant such as urea was largely suppressed upon interaction with CCMC self-aggregated nanoparticles. DS of cholesterol moiety significantly affected the interaction between BSA and CCMC self-aggregated nanoparticles.     

The synthesis and characterization of monodispersed chitosan-coated Fe3O4 nanoparticles via a facile one-step solvothermal process for adsorption of bovine serum albumin

Preparation of magnetic nanoparticles coated with chitosan (CS-coated Fe₃O₄ NPs) in one step by the solvothermal method in the presence of different amounts of added chitosan is reported here. The magnetic property of the obtained magnetic composite nanoparticles was confirmed by X-ray diffraction (XRD) and magnetic measurements (VSM). Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) allowed the identification of spherical nanoparticles with about 150 nm in average diameter. Characterization of the products by Fourier transform infrared spectroscopy (FTIR) demonstrated that CS-coated Fe₃O₄ NPs were obtained. Chitosan content in the obtained nanocomposites was estimated by thermogravimetric analysis (TGA). The adsorption properties of the CS-coated Fe₃O₄ NPs for bovine serum albumin (BSA) were investigated under different concentrations of BSA. Compared with naked Fe₃O₄ nanoparticles, the CS-coated Fe₃O₄ NPs showed a higher BSA adsorption capacity (96.5 mg/g) and a fast adsorption rate (45 min) in aqueous solutions. This work demonstrates that the prepared magnetic nanoparticles have promising applications in enzyme and protein immobilization.     

Preparation of Anti‐Nonspecific Adsorption Chitosan‐Based Bovine Serum Albumin Imprinted Polymers with Outstanding Adsorption Capacity and Selective Recognition Ability Based on Magnetic Microspheres

Bovine serum albumin (BSA)‐imprinted magnetic microspheres are successfully fabricated by a precipitation copolymerization, in which 2‐hydroxyethyl acrylate (HEA) and water‐soluble chitosan separately work as functional monomers and cross‐linking agents. Hydroxyl derived from HEA as well as hydroxyl, amino, and carboxyl groups, originating from chitosan on the surface of the prepared imprinted microspheres, can form hydrogen bonds and extra electrostatic interaction with proteins. The sulfobetaine methacrylate (SBMA) is introduced into the imprinted polymer as an anti‐protein segment to reduce the nonspecific adsorption and improve the selectivity. Detailed characterization demonstrates that the imprinted layer is about 10 nm, which is extremely beneficial for BSA identification and quality transmission. Furthermore, these microspheres also display an excellent selective adsorption of BSA (IF = 5.0). The results reveal that the prepared imprinted materials can be used as BSA biosensor or separation materials.     

Novel polysaccharides-based nanoparticle carriers prepared by polyelectrolyte complexation for protein drug delivery

Polyelectrolyte complexation, as one simple and promising method for preparing nanoparticles, is employed to find the use in the delivery of protein drugs. Using this method, we fabricated one kind of novel nanoparticles based on two natural polysaccharides, which are the negatively charged carboxymethyl pachyman (CMP) and the positively charged chitosan (CS). The major effect factors on the average particle size, polydispersity, and zeta potential of the nanoparticles were studied. The research indicated that the physicochemical properties of the nanoparticles were deeply affected by the molecular weight, concentration, and the ionic content of two polysaccharides. The mean particle size of CMP/CS nanoparticles was almost in the range of 100–200 nm for various preparation conditions. The morphology of nanoparticles characterized by a transmission electron microscope was spherical in shape with smooth surface structure. In order to study the feasibility of these nanoparticles as oral protein delivery carriers, the encapsulation efficiency of CMP/CS nanoparticles for bovine serum albumin (BSA) was evaluated for optimized condition. It turned out that the encapsulation efficiency of BSA-loaded CMP/CS nanoparticles varied from 30.1 to 52.9% depending on the initial loading concentration of BSA as well as the concentration of CMP and CS employed in particle formation, which indicated that the concentration of polymers and drugs were all contributed to the encapsulation efficiency of nanoparticles. This report opened up another interesting perspective to develop these natural polysaccharides with emerging new applications, which have great potentials in application in the nanoparticulate delivery system.     

Development of ultrasmall chitosan/succinyl β‐cyclodextrin nanoparticles as a sustained protein‐delivery system

In this article, we introduce a new method for preparing ultrasmall chitosan (CS)/succinyl β‐cyclodextrin (SCD) nanoparticles (NPs) intended for loading bovine serum albumin (BSA) as a model protein. The proposed method is based on the complex coacervation technique followed by ionotropic gelation with tripolyphosphate. SCD, an anionic derivative of cyclodextrin, was synthesized and used in CS‐based NPs to enhance the entrapment efficiency of BSA. The results show that with this approach, ultrasmall, compact, and neutralized NPs with a mean particle size near 30 nm were obtained. A high degree of protein entrapment in the NPs led to a significant improvement in the BSA release profile with a low initial burst release (ca. 3% w/v of the initially loaded BSA) and a sustained release over time. This enabled a suitable nanocarrier for long‐term protein delivery (30% release over 120 h). © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 39648.