复相乳化法制备海藻酸钙微球及其释放行为

采用复相乳化法制备了载牛血清白蛋白(BSA)的海藻酸钙微球,通过正交实验和单因素分析,以BSA包埋率、微球的载药率和平均粒径为考察指标,优化了该方法的制备参数,使最终制备的微球平均粒径小于10 mm,球形度较好,包埋率约70%,载药率达4%. 随着海藻酸钠质量分数的降低和BSA质量的增大,微球的包埋率下降、载药率升高、平均粒径减小. 微囊化BSA的体外释放曲线表明,该系统存在pH响应特性,尤其在磷酸缓冲液中,被包埋BSA的释放速率较快. 电泳结果表明,BSA的分子结构并未受制备过程的影响. 因此,该微囊化方法有望用于蛋白类药物的控释制剂,使其免受胃酸等的破坏,达到肠部释药的目的.     

乳化法制备海藻酸钙/聚组氮酸微胶囊

采用乳化法制备海藻酸钙微球及海藻酸钙/聚组氨酸载药微胶囊,并考察不同海藻酸钠浓度、氯化钙浓度对微球表面形态、粒径分布、载药性能及微胶囊控制释放性能的影响。结果表明海藻酸钠浓度主要影响微球的粒径大小,氯化钙浓度主要影响微球的分散程度及粒径分布,微球载药量均随海藻酸钠浓度及氯化钙浓度的增加而减小,所制备的微胶囊均无明显的突释现象。     

膨润土对海藻酸钠/壳聚糖凝胶微球性能的影响

为了得到一种对啶虫脒具有高负载率和良好的缓释性能的农药载体,以膨润土作为吸附剂,利用壳聚糖的成膜性,采用挤出外源凝胶法制备了啶虫脒凝胶微球。并通过FTIR、SEM、TG、溶胀实验和释药实验对其结构、形貌和性能进行表征。结果表明,所制得的凝胶微球的粒径为1.42～1.71 mm,膨润土可提高微球粒径与球形度,使啶虫脒的载药率和包封率分别由原来的4.16%和36.36%提升为4.91%和63.01%。壳聚糖与海藻酸钠通过静电作用形成了聚电解质复合物,辅助了钙离子交联,使啶虫脒的载药率和包封率分别由原来的4.16%和36.36%提升为5.23%和54.29%。膨润土表面含有大量的羟基,与海藻酸钠和壳聚糖形成氢键作用,可有效抑制海藻酸钙的大量溶胀,提高其缓释性能。     

阿维菌素海藻酸钙微球制备与表征

[目的]制备阿维菌素海藻酸钙微球,并评价其相关性能。[方法]采用内源乳化法制备阿维菌素海藻酸钙微球,以溶胀率、产率为考察指标,结合正交设计试验对微球的制备工艺进行优化,并利用光学显微镜和傅立叶变换红外光谱仪对微球进行了观察和表征。[结果]阿维菌素海藻酸钙微球最佳工艺为海藻酸钠和Span 80的质量浓度均为15 g/L、海藻酸钠与CaCO3质量比3∶1、水油两相体积比为1∶2。所制备的微球外观呈规则球形,载药率和包封率分别达到84.21%和20.16%。体外药物释放试验表明,阿维菌素海藻酸钙微球48 h累计释放率为78.61%。[结论]所制备的阿维菌素海藻酸钙微球具有良好的缓释性,提高了农药的利用率。     

肠靶向海藻酸钙基微胶囊的制备及控释性能研究

利用毛细管共挤出技术结合静电吸附和仿生硅化的方法,制备了海藻酸钙-壳聚糖/精蛋白/二氧化硅(ACPSi)复合微胶囊。ACPSi复合微胶囊的平均粒径约3.18 mm,单分散性好,囊壁最外层的二氧化硅层可抑制其在肠液pH环境中的溶胀,增强囊的机械稳定性。将羟丙甲基纤维素邻苯二甲酸酯(HPMCP)肠溶微球作为释药“微阀门”,嵌入囊壁可以更好地控制微胶囊的释药行为。以吲哚美辛为模型药物,当药物浓度为22.5 mg/ml时,ACPSi载药微胶囊在pH 2.5模拟胃液中3 h时累计释药率仅为0.33%,而转移至pH 6.8模拟肠液中19 h时累计释药率为77.78%;囊壁嵌入HPMCP微球后,22 h时累计释药率可提高约4%。因此,该复合微胶囊具有良好的肠靶向作用和控释特性,作为口服肠靶向缓控释制剂具有良好的应用前景。     

海藻酸钙/埃洛石载药微球的制备与缓释盐酸二甲双胍性能

缓释可提高药物利用率,降低其毒副作用。采用交联法制备了海藻酸钙/埃洛石载药微球,以载药微球对盐酸二甲双胍（MH）药物的包封率和缓释效果为考察对象,研究了载药微球的制备工艺和缓释性能,并通过SEM、FTIR和TGA对其结构进行了表征。结果表明：在交联温度为0℃、海藻酸钠用量为1g、埃洛石添加量为2g时,能得到较优的载药微球包封率（79.23%）。上述条件下制得的复合载药微球在pH=6.8的磷酸盐缓冲液中能有效缓释,且720min后缓释度可达85.83%,说明其具有较好的pH敏感性和缓释效果。SEM表明海藻酸钙颗粒与埃洛石在载药微球内部形成复合结构,FTIR表明MH主要以物理包埋的形式于载药微球中,TGA表明添加埃洛石可以提高复合材料在200℃以上的热稳定性。     

酮洛芬缓释微球的制备及其性能研究

制备酮洛芬缓释微球并对其性能进行研究。采用乳化交联法制备微球,正交试验优化微球的工艺处方,对微球从形态、粒径分布、DSC方面进行表征;用透析法进行体外释药实验,并对释药曲线进行拟合。结果表明,微球的最优工艺处方为壳聚糖浓度为2%,搅拌速度为1000r/min,乳化温度30℃,交联剂用量2.5%。制得的微球平均粒径为(1.42±0.24)μm,包封率为(82.2±2.2)%,DSC分析表明药物以非结晶形式分散于微球骨架中,体外释药曲线符合Higuchi方程,与市售缓释制剂相比,微球显示了较好的缓释特性,值得进一步研究。     

紫薯花色苷果胶/海藻酸钙复合凝胶球的制备及性能研究

采用离子凝胶法制备了荷载紫薯花色苷的果胶/海藻酸钙凝胶球,以弹性、硬度、紫薯花色苷包封率为评价指标,探讨氯化钙浓度、果胶与海藻酸钠比例、胶凝时间对指标的影响。结果表明,随着氯化钙浓度、果胶添加量的增大及胶凝时间延长,凝胶球的硬度和包封率增大。当果胶/海藻酸钠比为7∶1,氯化钙浓度为9%,胶凝时间为5 min时,此时制备的凝胶球硬度最大,弹性适度,包封率最大。SEM扫描电镜显示,凝胶球具有明显的核壳结构。溶胀和模拟胃肠液实验显示,凝胶球在碱性和肠液中易溶胀,在结肠中释放最大,达到54.8%。     

高载药量海藻酸钙/几丁聚糖微胶囊的性能

采用乳化固化法制备了平均粒径为820nm海藻酸钙微球,并制备了海藻酸钙/几丁聚糖微胶囊。以牛血清白蛋白(BSA)为模型药物,考察投药浓度、几丁聚糖分子量和浓度等对微胶囊载药量和药物释放的影响,发现其载药量最大可达40%以上,结果还显示这种微胶囊具有很好的体外缓释性能。     

紫薯花色苷果胶/海藻酸钙复合凝胶球的制备及性能研究

采用离子凝胶法制备了荷载紫薯花色苷的果胶/海藻酸钙凝胶球,以弹性、硬度、紫薯花色苷包封率为评价指标,探讨氯化钙浓度、果胶与海藻酸钠比例、胶凝时间对指标的影响。结果表明,随着氯化钙浓度、果胶添加量的增大及胶凝时间延长,凝胶球的硬度和包封率增大。当果胶/海藻酸钠比为7∶1,氯化钙浓度为9%,胶凝时间为5 min时,此时制备的凝胶球硬度最大,弹性适度,包封率最大。SEM扫描电镜显示,凝胶球具有明显的核壳结构。溶胀和模拟胃肠液实验显示,凝胶球在碱性和肠液中易溶胀,在结肠中释放最大,达到54.8%。     

Chitosan/calcium–alginate beads for oral delivery of insulin

A mild chitosan/calcium alginate microencapsulation process, as applied to encapsulation of biological macromolecules such as albumin and insulin, was investigated. The microcapsules were derived by adding dropwise a protein-containing sodium alginate mixture into a chitosan–CaCl₂ system. The beads containing a high concentration of entrapped bovine serum albumin (BSA) as more than 70% of the initial concentration were achieved via varying chitosan coat. It was observed that approximately 70% of the content is being released into Tris-HCl buffer, pH 7.4 within 24 h and no significant release of BSA was observed during treatment with 0.1M HCl pH 1.2 for 4 h. But the acid-treated beads had released almost all the entrapped protein into Tris-HCl pH 7.4 media within 24 h. Instead of BSA, the insulin preload was found to be very low in the chitosan/calcium alginate system; the release characteristics were similar to that of BSA. From scanning electron microscopic studies, it appears that the chitosan modifies the alginate microspheres and subsequently the protein loading. The results indicate the possibility of modifying the formulation in order to obtain the desired controlled release of bioactive peptides (insulin), for a convenient gastrointestinal tract delivery system. © 1996 John Wiley & Sons, Inc.     

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     

Preparation and in vitro evaluation of new pH‐sensitive hydrogel beads for oral delivery of protein drugs

New biodegradable pH‐responsive hydrogel beads based on chemically modified chitosan and sodium alginate were prepared and characterized for the controlled release study of protein drugs in the small intestine. The ionotropic gelation reaction was carried out under mild aqueous conditions, which should be appropriate for the retention of the biological activity of an uploaded protein drug. The equilibrium swelling studies were carried out for the hydrogel beads at 37°C in simulated gastric (SGF) and simulated intestinal (SIF) fluids. Bovine serum albumin (BSA), a model for protein drugs was entrapped in the hydrogels and the in vitro drug release profiles were established at 37°C in SGF and SIF. The preliminary investigation of the hydrogel beads prepared in this study showed high entrapment efficiency (up to 97%) and promising release profiles of BSA. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

Preparation and evaluation of poly(3‐hydroxybutyrate) microspheres containing bovine serum albumin for controlled release

The utility of the Poly(3‐hydroxybutyrate) (PHB) to encapsulate and control the release of bovine serum albumin (BSA), via microspheres, was investigated. Various preparing parameters, including polymer concentration in oil phase, emulsification concentration in external water phase, volume ratio of inner water phase to oil phase, and volume ratio of primary emulsion to external water phase were altered during the microspheres production. The effects of these changes on the morphological characteristics of the microspheres, size of the microspheres, drug loading, encapsulation efficiency, and drug release rates were examined. The diameter of the microspheres ranged from 6.9 to 20.3 μm and showed different degrees of porous structure depending on the different preparation parameters. The maximum and minimum BSA encapsulation efficiency within the polymeric microspheres were 69.8 and 7.5%, respectively, varying with preparation conditions. The controlled release characteristics of the microspheres for BSA were investigated in pH 7.4 media. The initial BSA burst release from 8.9 to 63.1% followed by constant slow release for 28 days was observed for BSA from BSA‐loaded microspheres and followed the Higuchi matrix model. So, the release behavior of microspheres showed the feasibility of BSA‐loaded microspheres as controlled release devices. Pristine BSA, pristine PHB microspheres, and BSA‐loaded microspheres were analyzed by Fourier transform infrared spectrophotometer, which indicated no interaction between BSA and PHB. Differential scanning calorimetry on BSA‐loaded microspheres indicated a molecular level dispersion of BSA in the microspheres. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008     

阿维菌素凝胶微球制备及其缓释性能研究

以壳聚糖(CS)和海藻酸钠(ALG)为包封材料,以阿维菌素(AVM)为芯材,采用锐孔法制备了阿维菌素-海藻酸钠-壳聚糖微球,考察了海藻酸钠质量分数、壳聚糖质量分数、氯化钙质量分数和芯壁体积比(质量分数1%的阿维菌素乳液与质量分数3%海藻酸钠溶液的体积比)对微球形态及包埋率的影响,利用SEM、FTIR等对微球结构及性质进行了表征,并考察了其在土壤中的缓释性能和释药机制。结果表明,经优化的制备条件为:海藻酸钠、壳聚糖及氯化钙的质量分数分别为3%、0.6%及5%,芯壁体积比为1∶2,制备的载药微球形状规整,成球性良好,粒径约0.7 mm,载药量31.65%,包埋率83.81%;红外光谱分析显示,芯壁材料之间除氢键外,没有发生化学作用。所制备的阿维菌素微球在土壤中具有缓释特性,42 h累积释药率达到82.06%,之后药物释放减缓。药物释放特性符合Riger-Peppas模型,释放机理为Fick扩散。     

Electrospray preparation of propranolol‐loaded alginate beads: Effect of matrix reinforcement on loading and release profile

In the present study, propranolol loaded‐calcium alginate beads were prepared from concentrated solutions of sodium alginate, using combined method of electrospray and ionotropic gelation. The objectives of the study were to increase the propranolol‐HCl loading and to decrease its initial burst release. However, the effects of voltage, nozzle diameter, flow rate, and concentration of sodium alginate on size of the beads and drug entrapment efficiency (DEE) were also investigated. The matrix of alginate beads was reinforced with dextran sulfate and/or coated with chitosan. The mean particle size of the beads, their swelling behavior, and drug entrapment efficiency were characterized. Furthermore, the drug release profiles from the prepared beads in simulated gastric fluid and intestinal fluid were evaluated and compared. Among the parameters that affected the electrospray of alginate, voltage had a pronounced effect on the size of beads. The size of beads was reduced to a minimum value on increasing the voltage. Furthermore, increasing the flow rate, alginate concentration, and nozzle diameter and decreasing the voltage led to improvement in DEE. Enhancing the alginate concentration as well as coating with chitosan and reinforcing with dextran sulfate led to increase of the encapsulation efficiency and therefore decrease of the drug release rate in both pHs. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 41334.     

快速膜乳化与热固化法制备粒径均一的pH敏感壳聚糖季铵盐凝胶微球

以具有升温自固化特性的壳聚糖季铵盐/甘油磷酸钠混合溶液为水相,利用快速膜乳化与热固化法制备了粒径均一、pH敏感的壳聚糖季铵盐凝胶微球,考察了跨膜压力、水油相组成、水油相体积比及微孔膜孔径等对微球粒径、结构和药物包埋率的影响. 结果表明,得到粒径698±57.33, 1145±71.48, 2021±53.63及3984±191.72 nm、粒径分布窄(多分散系数<0.1)、药物包埋率高达75.49%±2.62%的凝胶微球. 所制微球生物相容性好,有明显的pH敏感性,中性和碱性环境下结构稳定,药物缓释,pH=7.4时24 h内药物累计释放率为34.6%;酸性环境下微球崩解,药物快速释放,pH=5.5时1 h内药物累计释放率高达79.6%.     

Alginate/carboxymethyl chitosan composite gel beads for oral drug delivery

This paper reports the synthesis of pH-sensitive gel beads derived from alginate (SA) and carboxymethyl chitosan (CMCS) for drug delivery. The composite SA/CMCS gel beads were prepared by dual ionic gelation: one ionic gelation between SA and Ca²⁺ and another one between CMCS and β-Sodium glycerophosphate (β-GP). The structure properties of hydrogel beads were characterized by SEM, IR and TG technique. The influence of the polymer composition and cross-linkers on the gel swelling property was investigated. When the concentration of CMCS and SA were 3 % and the volume ratio was 1:2, the swelling rate of gel beads crosslinked by β-GP and CaCl₂ solution can increase up to 31.2 and the swelling time can reach 10.5 h. In the drug release study, bovine serum albumin (BSA) was chosen as model drugs. The results indicated that BSA released slowly from the gel beads at pH 1.2 and the release ratio was about 10 %. At pH 7.4, the amounts of BSA released increased significantly as compared to those released at pH 1.2 and the total release time was extended to 11 h. The composite gel system demonstrates sustained release profile and pH sensitivity, which can be considered as good candidates for oral drug delivery systems.