双乳化-凝胶法制备单分散海藻酸钙微球及其载BSA研究

采用双乳化-凝胶法制备了单分散的海藻酸钙凝胶微球,并通过正交试验系统考察了海藻酸钠浓度、氯化钙浓度、表面活性剂浓度、搅拌速度和油水比对海藻酸钙凝胶微球粒径及形貌的影响。在优化的条件下,制备出了平均粒径为4μm、单分散和球形度好的海藻酸钙凝胶微球。包埋模型药物牛血清白蛋白(BSA)的过程中,以去离子水作为洗涤液洗涤海藻酸钙微球时,BSA的包封率仅为13%左右;当水洗液的pH值为3.2时,BSA的包封率提高到66%左右,载药率可达16%,这是海藻酸钙pH值响应溶胀和BSA与海藻酸盐之间静电作用的结果。微球中BSA的体外释放曲线表明,该系统具有在模拟胃液中释药速率慢、释药量低、模拟肠液中释药迅速的特性。因此,双乳化-凝胶法制备海藻酸钙微球有望成为制备蛋白类药物控释制剂的一种新方法,以达到靶向快速给药的目的。     

快速膜乳化法制备载生长激素释放肽-6的PLGA微球

采用快速膜乳化法制备了聚(乳酸-羟基乙酸)(PLGA)微球,得到制备PLGA微球的优化条件为：过膜压力5 kPa,水相中PVA浓度19 g/L,油/水相体积比1:10,该条件下所制空白微球的平均粒径约为24 mm,粒径分布系数Span<0.7. 在此基础上制备载生长激素释放肽-6(GHRP-6)微球,油相乳化剂浓度2.5 g/L、外水相中NaCl浓度10 g/L条件下所制载GHRP-6微球包埋率最高可达85%,初乳制备方式对药物包埋率及体外释放行为均有较大影响,超声法制备的初乳所得微球内部结构紧密,药物包埋率较高(85%),但释药缓慢;而均质法制备的初乳所得微球内部结构疏松,药物包埋率较低(76.8%),但在体外释放更完全.     

快速膜乳化法制备载紫杉醇聚乳酸类微球

采用快速膜乳化法、均质乳化法和超声法制备了聚乳酸(PLA)空白微球,比较了3种方法所制微球的均一性.采用均质乳化法和超声法制备的PLA微球平均粒径分别为1.022和0.987μm,多分散系数分别为0.133和0.145,而快速膜乳化法制备的PLA微球平均粒径为0.906μm,多分散系数为0.005.在此基础上,采用快速膜乳化法制备了聚乳酸、聚(乳酸-羟基乙酸)共聚物(PLGA)和聚(乳酸-聚乙二醇)二嵌段共聚物(PELA)载紫杉醇微球,平均粒径分别为0.906,0.987和1.015μm,多分散系数均为0.005,载药率分别为3.89%,4.93%和3.18%,包埋率分别为63.2%,71.6%和51.3%,在磷酸盐缓冲液中释放60d后,PLGA微球的药物释放率为83.87%,PLA微球为50.25%,PELA微球为41.27%.     

膜乳化法与复乳法结合制备粒径均一的PELA载溶菌酶微球

采用快速膜乳化技术与复乳-溶剂去除法制备了尺寸均一的单甲氧基聚乙二醇-聚-DL-乳酸(PELA)载溶菌酶微球,比较了膜材种类和有机溶剂类型对微球中药物包埋率和活性保持的影响. 研究结果表明,该方法能快速制备粒径均一的载药微球,在油相与外水相体积比为1:6的条件下,微球粒径分布系数小于20%,而且该方法对膜材和有机溶剂有很好的普适性. 以PELA为膜材、乙酸乙酯为有机溶剂,采用溶剂扩散法制备的载药微球包埋率高达95.7%,并且能保持高的活性.     

季铵化两亲性壳聚糖衍生物载药性质研究

合成新型季铵化两亲性壳聚糖衍生物(DEAE-CMC)。用乳化交联固化法制备DEAE-CMC/VB12载药微球。用激光粒径仪、扫描电镜对微球的大小和形态进行表征。载药微球的平均粒径为4.53μm。在pH=7.4磷酸盐缓冲溶液中,DEAE-CMC/VB12载药微球体外药物释放达到平衡时间为60 h,药物包封率为33.70%,载药量为12.47%,平衡时药物累积释放率为56.30%。     

小檗碱壳聚糖微球制备及其抗真菌活性测定

采用乳化-化学交联法制备了负载小檗碱的壳聚糖微球. 以正交实验对微球形态、粒径、药物包封率和载药率等指标进行了制备工艺条件优化. 显微镜和电镜观察显示微球球形良好,表面光滑,平均粒径约15 mm,包封率为78.98%,载药率为4.78%. 持续30 d的药物释放实验表明,小檗碱可从微球中缓慢释放. 利用生长速率法测定了微球对3种重要植物病原真菌的抑制作用,5 mg/mL微球对番茄早疫病菌(Alternaria solani)的抑菌率达65%.     

丝素-羟丙基壳聚糖微球的结构和释药性能

以胰岛素为目标药物,以丝素(SF)和羟丙基壳聚糖(HPCS)为包药材料,复凝聚法制备SF-HPCS载药微球。采用红外光谱(FTIR)、扫描电镜(SEM)、X射线衍射(XRD)、热重分析(TGA)等对载药微球的结构、外部形貌及热性能等进行了表征。结果表明,所制备的载药微球表面密实,平均粒径22.4μm,呈正态分布;载药微球对胰岛素的包埋率达73.6%,大于HPCS载药微球(64.3%)及壳聚糖(CS)载药微球(57.1%);SF-HPCS载药微球在人工胃液中4h内累计释药率为21.3%,在人工肠液中24h内累计释药率达81.2%,48h累计释药率为92.2%,释放过程平稳、缓慢。     

壳聚糖聚乙烯醇复合载药微球的制备

以壳聚糖(CS)为基质,通过聚乙烯醇(PVA)的引入制备壳聚糖聚乙烯醇复合载体可以分别采用室温和高温酸催化反应两种方法制备出释药性能和结构形态不同的两种复合载药微球Ⅰ和Ⅱ。其中壳聚糖/聚乙烯醇复合载药微球Ⅰ的制备工艺是调节壳聚糖和聚乙烯醇质量比6/5,复合微球Ⅰ的平均粒径1～20μm,载药量13%,LVFX体外12h累积释放80%。而壳聚糖/聚乙烯醇复合载药微球Ⅱ的平均粒径1.69μm,载药量17.1%,LVFX体外6hr基本完全释放。     

快速膜乳化法制备胸腺法新长效缓释微球

采用快速膜乳化技术结合溶剂蒸发法制备以生物可降解聚乳酸-羟基乙酸(PLGA)为载体的胸腺法新载药微球,考察了PLGA分子量、油相中PLGA和乳化剂浓度、外水相pH值和内水相体积等对微球包埋率和粒径的影响. 结果表明,制备粒径均一的PLGA载药微球的优化条件为：PLGA分子量51 kDa,油相中PLGA和乳化剂浓度为100和10 g/L,内水相体积0.5 mL,外水相pH值为3.5. 该条件下所制载药微球粒径均一性好(Span<0.7),药物包埋率高达80%以上,突释率24 h内低于20%,线性持续稳定释药时间长达30 d.     

井冈霉素载药二氧化硅空心微球的原位制备及缓释性能评价

利用正硅酸乙酯在W/O乳液中的原位水解聚合,成功制备了包埋井冈霉素的二氧化硅载药空心微球. 对所得产品进行了SEM, XRD, FT-IR和粒径分布等分析,结果表明,载药空心微球粒径分布窄,范围在7.5~15 mm,球状形貌良好,具有空心结构,呈无定型态. 热重分析表明载药空心微球的药物负载量约为31.9%(w),缓释溶出实验显示载药空心微球药物释放持续时间约240 min,最终释放量达总载药量的90%以上.     

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     

猪脾脏转移因子壳聚糖-海藻酸钠微囊的制备及其性能

以壳聚糖-海藻酸钠为囊材,采用乳化-外部凝胶法制备猪脾脏转移因子壳聚糖-海藻酸钠微囊,并研究了其粒径、载药量、包封率、体外释药等性质. 结果表明,经优化工艺所制微囊球形度良好,平均粒径11.05 mm,平均载药量11.60 mg/g,平均包封率60.8%,在磷酸缓冲液(pH=7.4)中的释药曲线方程为ln(1-Q)=-0.0692t-0.6449 (R2=0.9876),符合一级动力学方程. 该制备工艺简单,所制猪脾脏转移因子微囊具有良好的溶胀性能和缓释性能.     

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     

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。     

羧甲基壳聚糖-蓖麻油基聚氨酯农药缓释微球的制备及性能

以羧甲基壳聚糖（CMCS）、蓖麻油（CO）和异佛尔酮二异氰酸酯（IPDI）为原料,自乳化法制备了羧甲基壳聚糖-蓖麻油基聚氨酯微球（CO-CMCS-PU）,通过分子自组装法负载阿维菌素（AVM）得到载药微球（CO-CMCS-PU@AVM）。采用FTIR、1HNMR、SEM、TGA等对产品结构及形貌进行表征,并探究了不同药量载药微球的包封率、缓释性能、抗紫外性能、叶面接触角和黏附性能。结果表明,相比AVM分散液,紫外照射后载药微球中AVM的保留率提高到43%,说明CO-CMCS-PU载体的抗紫外性能良好;载药微球比AVM分散液在黄瓜叶面上的接触角降低了20%以上,滞留量提高了40%以上,说明其在叶面上有较好的黏附性和润湿性;载药微球包封率可达80%以上,具有良好的缓释和pH响应释放性能,释药行为符合First-order动力学模型,药物释放受Fickian扩散控制。     

Enhanced gastric retention and drug release via development of novel floating microspheres based on Eudragit E100 and polycaprolactone: synthesis and in vitro evaluation

Eudragit E 100 and polycaprolactone (PCL) floating microspheres for enhanced gastric retention and drug release were successfully prepared by oil in water solvent evaporation method. Metronidazole benzoate, an anti-protozoal drug, was used as a model drug. Polyvinyl alcohol was used as an emulsifier. The prepared microspheres were observed for % recovery, % degree of hydration, % water uptake, % drug loading, % buoyancy and % drug release. The physico-chemical properties of the microspheres were studied by calculating encapsulation efficiency of microspheres and drug release kinetics. Drug release characteristics of microspheres were studied in simulated gastric fluid and simulated intestinal fluid i.e., at pH 1.2 and 7.4 respectively. Fourier transform infrared spectroscopy was used to reveal the chemical interaction between drug and polymers. Scanning electron microscopy was conducted to study the morphology of the synthesized microspheres.     

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.     

Encapsulation of anthocyanin with gelatin-alginate carrier by a specially designed ultrasonic encapsulator with adjustable frequency

Anthocyanins are of increasing interest for food applications due to their health benefits. However, their poor stability and susceptibility to unfavorable environmental conditions may limit their application. Microencapsulation offers enhanced stability and controlled release properties. The aim was designing an ultrasonic encapsulator with a variable frequency ultrasonic driver to encapsulate black carrot and mahaleb anthocyanins. First, a double-channel variable frequency and power adjustable ultrasonic driver and atomizer head were designed. The cooled gelation technique was used to encapsulate anthocyanin in an alginate-gelatin complex. Freeze-drying and air-drying techniques were used for drying of microcapsules. Encapsulation parameters were atomization frequency, alginate, and anthocyanin concentrations. The capsules were characterized by encapsulation efficiency, particle diameter, and controlled release rates. Controlled release tests were performed at two different temperatures and pH values. Encapsulation efficiency was 87%–95%, mean diameters were between 69 and 95 μm. Maximum release rates were obtained from freeze-dried mahaleb anthocyanin capsules. Release rates increased with increasing temperature and pH values. In addition, the experimental results showed that the increase in the amount of alginate used in encapsulation decreased the release rate. Moreover, the results proved that the designed encapsulator can be used for encapsulation in fields such as food, pharmaceuticals, polymers, chemistry, and materials.