Formulation and Characterization of Formaldehyde Cross-linked Degradable Starch Microspheres Containing Terbutaline Sulfate

ABSTRACT

Preparation of starch microspheres using epichlorohydrin is a time consuming method and requires around 18 hr for cross-linking reaction. To reduce reaction time, terbutaline sulfate (TBS) loaded degradable starch microspheres (DSM) were prepared using formaldehyde as the cross-linking agent. All microspheres were spherical in shape and had a porous, rough surface with a mean particle size of 18–24 μm. Whatever the cross-linking time, it was seen that the release of the TBS was not complete during the release experiments. The influence of enzyme on the degradation of microspheres was moderate. Following intravenous administration, initial uptake of microspheres by the lung was higher than those of other organs.     

反应条件对接枝交联双重改性淀粉胶黏剂性能的影响

以玉米淀粉为原料,过硫酸铵( APS)与亚硫酸氢钠( NaHSO3 )为引发剂,丙烯酰胺( AM)与丙烯酸丁酯(BA)为接枝单体,环氧氯丙烷(ECH)为交联剂,制得了接枝交联双重改性淀粉基木材胶黏剂。 采用红外光谱对样品进行了表征,并研究了 AM 与 BA 质量比、APS 与 NaHSO3 质量比、反应温度、反应时间对淀粉基木材胶黏剂胶合强度及耐水性的影响。 实验结果表明,AM 与 BA 的接枝改性可以提高淀粉基木材胶黏剂胶合强度及耐水性,红外光谱证实 AM 和 BA 与淀粉发生了接枝反应。     

Preparation and blood coagulation evaluation of chitosan microspheres

Cross-linked chitosan microspheres (40–100 μm) with smooth surface were prepared by the methods of emulsification and ethanol coagulant. FTIR results showed that the cross-linking reaction occurred on the amino groups of chitosan molecules. The swelling characteristic of chitosan microspheres was influenced by the environment pH, being generally greater at low rather than higher pH values. The coagulation properties of chitosan microspheres were evaluated by dynamic blood clotting, platelet adhesion and activation, erythrocyte adhesion, hemolysis, and protein absorption assays. Chitosan microspheres can shorten the clotting time and induce the adhesion and activation of platelets. But the shortening of clotting time by chitosan microspheres may be related to not only platelet aggregation, but also erythrocyte aggregation. Take together, chitosan microspheres may be potential use as thrombospheres.     

N,N''''-亚甲基双丙烯酰胺交联淀粉微球的合成与表征

以可溶性淀粉为原料,K2S2O8-Na2SO3为引发剂,用反相悬浮法合成了N,N'-亚甲基双丙烯酰胺交联淀粉微球CSM.研究了交联剂质量分数、反应温度和引发剂浓度对微球产率、溶胀度、平均粒径的影响规律.用扫描电镜观测了样品形貌,用FT-IR对其结构进行了表征,用XRD、DSC以及TGA对其物理性质进行了分析.结果表明,所合成的交联淀粉微球形态圆整,表面光滑,粒度均匀,微球中存在酰氨基结构.与可溶性淀粉相比,淀粉微球结晶度降低,热稳定性增加.     

交联剂对可膨胀小球制备的影响

以丙烯腈为主要单体,以氢氧化镁为无机分散剂,采用常压聚合法,制备了膨胀倍率达到20-30倍的可膨胀小球。系统研究了二丙二醇二丙烯酸酯(DPGDA)、三缩丙二醇二丙烯酸酯(TPGDA)、新戊二醇二丙烯酸酯(NPGDA)、三羟甲基丙烷三丙烯酸酯(TMPTA)和二乙烯基苯(DVB)等5种交联单体对可膨胀小球制备的影响。通过扫描电子显微镜、热重分析、交联密度测定等手段研究了可膨胀小球的形貌、粒径、发泡剂的含量、交联密度、发泡倍率。确定DPGDA为最佳的交联剂种类,用量为1.7%。采用DPGDA作为交联剂的小球既具有较完好的球状形貌,又有较小的粒径,较高的发泡剂含量和较高的交联度,膨胀倍率可达30倍。     

三氯化铁替代硼砂对氧化淀粉胶粘剂性能的影响

目的为了改善氧化淀粉的综合性能。方法以交联剂三氯化铁替代硼砂,采用高锰酸钾氧化法制备了无硼砂淀粉,并研究了交联剂三氯化铁用量、无机填料、高聚物等对氧化淀粉胶粘剂性能(黏度、初粘强度、防水性、粘合强度等)的影响。结果替代后的氧化淀粉胶粘剂不仅具有更好的黏度与初粘强度,而且其与无机填料以及高聚物均具有更好的兼容性。结论三氯化铁替代硼砂后所制备的氧化淀粉胶的防水性、粘结强度更好。     

阴离子型淀粉微球的制备研究

本文先以可溶性淀粉为原料,以表氯醇为交联剂,采用逆相悬浮交联聚合法制得中性淀粉微球,然后用Na3P3O9作交联剂进行第二次交联和阴离子化,制得阴离子型淀粉微球。分析了不同因素对中性淀粉微球的粒径及其分布的影响,优化了制备的工艺条件。对产品的物理化学性质进行了表征。实验结果表明:此制备工艺稳定,有良好的应用研究前景。     

Starch-based microspheres produced by emulsion crosslinking with a potential media dependent responsive behavior to be used as drug delivery carriers

This paper describes the development and characterization of starch microspheres for being used as drug delivery carriers in tissue engineering applications. The developed starch microspheres can be further loaded with specific growth factors and immobilized in scaffolds, or administrated separately with scaffolds. Furthermore and due to the processing conditions used, it is expected that these microspheres can be also used to encapsulate living cells. The aim of this study was to evaluate the efficacy of this methodology for further studies with biologically active agents or living cells. The starch microspheres were prepared using an emulsion crosslinking technique at room temperature to allow for the loading of biologically active agents. A preliminary study was performed to evaluate the incorporation of a model drug (nonsteroidal anti-inflammatory drug-NSAID) and investigate its release profile as function of changes in the medium parameters, such as ionic strength and pH. The developed starch-based drug delivery system has shown to be dependent on the ionic strength of the release medium. From preliminary results, the release seems to be pH-dependent due to the drug solubility. It was found that the developed microspheres and the respective processing route are appropriate for further studies. In fact, and based in the processing conditions and characterization, the developed system present a potential for the loading of different growth factors or even living cells on future studies with these systems for improving bone regeneration in tissue engineering, especially because the crosslinking reaction of the microspheres takes place at room temperature.     

淀粉微球的制备及其工艺的优化

以可溶性淀粉为原料,N,N'-亚甲基双丙烯酰胺(MBAA)及环氧氯丙烷(ECH)为交联剂,利用反相悬浮聚合法合成了淀粉微球,通过单因素实验和正交实验对制备工艺进行了优化,利用粒度分析仪、红外光谱仪对产物进行了表征.结果表明:MBAA用量及油水相体积比是影响微球粒径的主要因素;所得微球粒度分布范围较窄,具有多种活性基团,可用作药物载体和吸附剂.     

氧化锌自组装微球的微波水热合成与影响因素

以Zn(NO3)2.6H2O和聚乙二醇(PEG,Mn=2000)为原料,采用微波水热法制备出了结晶性能良好的ZnO微球。利用XRD、EDS、SEM、TEM对样品进行了表征,并系统研究了微波水热过程中辐照时间、水热温度、表面活性剂和超声处理等因素对产物形貌和结构的影响。实验表明,ZnO微球是由很多直径约300nm,长1μm的ZnO棒自组装而成,微球直径约为2μm,自组装结构的形成可能与PEG模板的导向作用有关。延长微波辐照时间,ZnO微球的直径有所增加,微球结构的完整性受微波水热温度影响较大。     

Resistant starch as a carrier for oral colon-targeting drug matrix system

In this study, a novel tablet of protein drug matrix for colon targeting was developed using resistant starch as a carrier prepared by pre-gelatinization and cross-linking of starch. The effects of pre-gelatinization and cross-linking on the swelling and enzymatic degradation of maize starch as well as the release rate of drug from the matrix tablets were examined. Cross-linked pre-gelatinized maize starches were prepared by double modification of pre-gelatinization and cross-linked with POCl₃, and bovine serum albumin was used as a model drug. For in vitro drug release assays, the resistant starch matrix tablets were incubated in simulated gastric fluid, simulated intestinal fluid and simulated colonic fluid, respectively. The content of resistant starch and swelling property of maize starch were increased by pre-gelatinization and cross-linking, which retarded its enzymatic degradation. Drug release studies have shown that the matrix tablets of cross-linked pre-gelatinized maize starch could delivery the drug to the colon. These results indicate that the resistant starch carrier prepared by pre-gelatinization and cross-linking can be used for a potential drug delivery carrier for colon-targeting drug matrix delivery system.     

添加剂辅助水热热解制备尺寸可控纳米孔碳微球

以KCl和HCl为添加剂,以果糖和淀粉为前躯体,通过水热处理和后续热解制备碳微球,探讨添加剂的作用机制。结果表明:碳微球具有纳米孔隙结构和表面含氧官能团。在2种前躯体中,添加剂均能促使具有规则球形的微球尺寸呈不同幅度的增大,平均直径控制在0.53～6.67μm之间。碳微球的形状和尺寸源于水热处理,而热解促使微球的结构由聚合物向玻璃碳转变,同时伴随着超过20%的尺寸收缩和近50%的质量损失。在水热反应过程中,氯化氢主要促进前期的多糖水解动力学以及单糖脱水与分裂动力学,而氯化钾主要加速后期微球的生长动力学。微球的生长涉及2种主要模式:构造单元交联生长和微粒合并生长。     

A novel method for the preparation of biodegradable microspheres for protein drug delivery.

Microspheres are potential candidates for the protein drug delivery. In this work, we prepared polymer-coated starch/bovine serum albumin (BSA) microspheres using co-axial electrohydrodynamic atomization (CEHDA). First, starch solution in dimethyl sulphoxide (DMSO) was prepared and then an aqueous solution of BSA was added to it to make a starch-BSA solution. Subsequently, this solution was made to flow through the inner capillary, while the polymer, polydimethylsiloxane (PDMS), flowed through the outer capillary. On collection, filtration and subsequent drying, near-monodisperse microspheres of 5-6microm in size were obtained. The microspheres were characterized by Fourier-transform infrared (FT-IR) spectroscopy and scanning electron microscopy. Cumulative BSA release was investigated by UV spectroscopy. BSA structure and activity was preserved in the microspheres and its release in 0.01M phosphate buffered saline (PBS) was studied over a period of 8 days. There was an initial burst with 32wt% of total BSA released in 2h. Overall 75wt% of BSA was released over a 7 day period.     

Preparation of novel cationic copolymer microspheres and evaluation of their function by in vitro and in vivo tests as pH-sensitive drug carrier systems

Novel pH-sensitive copolymer microspheres containing methylacrylic acid and styrene cross-linking with divinylbenzene were synthesized by free radical polymerization. The microspheres that were formed were then characterized by Fourier-Transform infrared (FT-IR) spectroscopy, differential scanning calorimetry (DSC), size analysis, and X-ray analysis. The copolymer microspheres showed pulsatile swelling behavior whenthe pH of the media changed. The pH-sensitive microspheres were loaded with diltiazem hydrochloride (DH). The release characteristics of the free drug and the drug-loaded microspheres were studied under both simulated gastric conditions and intestinal pH conditions. The in vivo evaluation of the pulsatile preparation was subsequently carried out using beagle dogs as experimental subjects. The results demonstrated that the drug release exhibited a pulsatile character both in vitro and in vivo.     

The behaviour of selected yttrium containing bioactive glass microspheres in simulated body environments

The study aims at the manufacture and investigation of biodegradable glass microspheres incorporated with yttrium potentially useful for radionuclide therapy of cancer. The glass microspheres in the SiO₂–Na₂O–P₂O₅–CaO–K₂O–MgO system containing yttrium were prepared by conventional melting and flame spheroidization. The behaviour of the yttrium silicate glass microspheres was investigated under in vitro conditions using simulated body fluid (SBF) and Tris buffer solution (TBS), for different periods of time, according to half-life time of the Y-90. The local structure of the glasses and the effect of yttrium on the biodegradability process were evaluated by Fourier Transform Infrared (FT-IR) spectroscopy and Back Scattered Electron Imaging of Scanning Electron Microscopy (BEI-SEM) equipped with Energy Dispersive X-ray (EDX) analysis. UV–VIS spectrometry and Inductively Coupled Plasma Mass Spectrometry (ICP-MS) was used for analyzing the release behaviour of silica and yttrium in the two used solutions. The results indicate that the addition of yttrium to a bioactive glass increases its structural stability which therefore, induced a different behaviour of the glasses in simulated body environments.     

Colorectal cancer targeted Irinotecan-Assam Bora rice starch based microspheres: a mechanistic,pharmacokinetic and biochemical investigation

The purpose of this investigation was to evaluate the colon-targeted Irinotecan Hydrochloride (ITC-HCl) loaded microspheres by pharmacokinetic and biochemical studies. The microspheres were prepared by double emulsion solvent evaporation method with natural polymer Assam Bora rice starch. The microspheres were characterized for their micromeritics properties, incorporation efficiency, in vitro and in vivo drug release studies. The release study confirmed the insignificant release of ITC-HCl in physiological condition of stomach and small intestine and major drug release in the caecal content. In vivo release study of the optimized microsphere was compared with immediate release (IR) ITC-HCl. ITC-HCl was distributed predominantly in the upper GI tract from the IR, whereas ITC-HCl was distributed primarily to the lower part of GI tract from the microspheres formulation. Enhanced levels of liver enzymes were found in animals given IR ITC-HCl as well as augmented levels of serum albumin, creatinine, leucocytopenia and thrombocytopenia was also observed. In summary, Assam Bora rice starch microspheres exhibit slow and extended release of ITC-HCl over longer periods of time with reduced systemic side-effects.     

Distribution of Etoposide-Loaded Hydrophilic Albumin Microspheres in Mice

Hydrophilic albumin microspheres of etoposide were prepared by the emulsion polymerization technique using glutaraldehyde as the cross-linking agent. The microspheres prepared had a mean diameter of 1.5 μm. The microspheres were injected into mice by the intravenous route. In all, 12 mice were selected for the study, out of which 10 were given the drug-loaded microspheres and 2 were kept as solvent control. The mice were sacrificed after 24 hr and the accumulation of drug was determined in lungs, liver, and kidney.     

Preparation of Novel Cationic Copolymer Microspheres and Evaluation of Their Function by In Vitro and In Vivo tests as Ph-Sensitive Drug Carrier Systems

ABSTRACT

Novel pH-sensitive copolymer microspheres containing methylacrylic acid and styrene cross-linking with divinylbenzene were synthesized by free radical polymerization. The microspheres that were formed were then characterized by Fourier-Transform infrared (FT-IR) spectroscopy, differential scanning calorimetry (DSC), size analysis, and X-ray analysis. The copolymer microspheres showed pulsatile swelling behavior whenthe pH of the media changed. The pH-sensitive microspheres were loaded with diltiazem hydrochloride (DH). The release characteristics of the free drug and the drug-loaded microspheres were studied under both simulated gastric conditions and intestinal pH conditions. The in vivo evaluation of the pulsatile preparation was subsequently carried out using beagle dogs as experimental subjects. The results demonstrated that the drug release exhibited a pulsatile character both in vitro and in vivo.     

Development of novel interpenetrating network gellan gum-poly(vinyl alcohol) hydrogel microspheres for the controlled release of carvedilol

Novel interpenetrating polymeric network microspheres of gellan gum and poly(vinyl alcohol) were prepared by the emulsion cross-linking method. Carvedilol, an antihypertensive drug, was successfully loaded into these microspheres prepared by changing the experimental variables such as ratio of gellan gum:poly(vinyl alcohol) and extent of cross-linking in order to optimize the process variables on drug encapsulation efficiency, release rates, size, and morphology of the microspheres. Formation of interpenetrating network and the chemical stability of carvedilol after preparing the microspheres was confirmed by Fourier transform infrared spectroscopy. Differential scanning calorimetry and x-ray diffraction studies were made on the drug-loaded microspheres to investigate the crystalline nature of the drug after encapsulation. Results indicated a crystalline dispersion of carvedilol in the polymer matrix. Scanning electron microscopy confirmed the spherical nature and smooth surface morphology of the microspheres produced. Mean particle size of the microspheres as measured by laser light scattering technique ranged between 230 and 346 µm. Carvedilol was successfully encapsulated up to 87% in the polymeric matrices. In vitro release studies were performed in the simulated gastric fluid or simulated intestinal fluid. The release of carvedilol was continued up to 12 h. Dynamic swelling studies were performed in the simulated gastric fluid or simulated intestinal fluid, and diffusion coefficients were calculated by considering the spherical geometry of the matrices. The release data were fitted to an empirical relation to estimate the transport parameters. The mechanical properties of interpenetrating polymeric networks prepared were investigated. Network parameters such as molar mass between cross-links and cross-linking density for interpenetrating polymeric networks were calculated.     

Development of Novel Interpenetrating Network Gellan Gum-Poly(vinyl alcohol) Hydrogel Microspheres for the Controlled Release of Carvedilol

Novel interpenetrating polymeric network microspheres of gellan gum and poly(vinyl alcohol) were prepared by the emulsion cross-linking method. Carvedilol, an antihypertensive drug, was successfully loaded into these microspheres prepared by changing the experimental variables such as ratio of gellan gum:poly(vinyl alcohol) and extent of cross-linking in order to optimize the process variables on drug encapsulation efficiency, release rates, size, and morphology of the microspheres. Formation of interpenetrating network and the chemical stability of carvedilol after preparing the microspheres was confirmed by Fourier transform infrared spectroscopy. Differential scanning calorimetry and x-ray diffraction studies were made on the drug-loaded microspheres to investigate the crystalline nature of the drug after encapsulation. Results indicated a crystalline dispersion of carvedilol in the polymer matrix. Scanning electron microscopy confirmed the spherical nature and smooth surface morphology of the microspheres produced. Mean particle size of the microspheres as measured by laser light scattering technique ranged between 230 and 346 µm. Carvedilol was successfully encapsulated up to 87% in the polymeric matrices. In vitro release studies were performed in the simulated gastric fluid or simulated intestinal fluid. The release of carvedilol was continued up to 12 h. Dynamic swelling studies were performed in the simulated gastric fluid or simulated intestinal fluid, and diffusion coefficients were calculated by considering the spherical geometry of the matrices. The release data were fitted to an empirical relation to estimate the transport parameters. The mechanical properties of interpenetrating polymeric networks prepared were investigated. Network parameters such as molar mass between cross-links and cross-linking density for interpenetrating polymeric networks were calculated.