5-氟尿嘧啶明胶微球的制备、表征及释药性能

为了获得粒径为50～100μm的5-氟尿嘧啶／明胶微球（5-Fu／GMs）,采用乳化一化学交联法,讨论了5-Fu用量、乳化剂浓度和水／油比等因素对微球平均粒径、载药量及包封率等的影响。结果表明,5-Fu／明胶质量比为0．5,乳化剂浓度为0．5％和水／油相体积比为1／10时,可获得最大的载药量30．1％和包封率90．2％。体外释药性能表明5-氟尿嘧啶明胶微球具有明显的药物缓释作用。     

壳聚糖-明胶载药微球的制备及释放性能

以壳聚糖（Cs）和明胶（Gel）为原料,采用乳液凝聚法制备了对药物具有缓释作用的微球。以异喹啉为模拟药物,分别通过丙酮浸泡载药／常温干燥法和盐酸浸泡载药／氢氧化钠再生／冷冻干燥法,制得不同载药量的微球,并对其包封率和释放行为进行了研究。结果表明,当戊二醛（GD）与壳聚糖（Cs）的质量比为0．40～0．53,载药量在20％～30％（质量分数）之间时,壳聚糖-明胶载药微球15h后释放75％左右,包封率可以达到40％～50％,为将壳聚糖。明胶共混微球应用于生物医学领域提供了试验基础。     

5-氟尿嘧啶/明胶纳米载药微球的制备及体外性能研究

目的：以5-氟尿嘧啶(5-FU)为模型药物,明胶为载体材料,制备5-氟尿嘧啶/明胶纳米载药微球,探究药物的缓释效果和抗肿瘤性能。方法：“单凝聚相法”制备明胶纳米载药微球;透射电镜（TEM）和粒径分析仪（DLS）分析纳米微球的形貌、粒径分布情况;计算其包封率和载药量,并对其体外缓释效果和抗肿瘤性能进行研究。结果：明胶纳米微球的表面形态良好,分散均一,平均粒径65.1?2.1 nm,明胶纳米微球的包封率为23.5?1.9 %,载药量为69.7?0.5 %;明胶微球具有良好的缓释性能,Higuchi方程对微球的体外药物释放情况拟合度较高。四甲基偶氮唑蓝实验结果表明,5-FU/明胶微球对胃癌细胞(SGC7901)具有明显的抑制作用。结论：5-FU/明胶微球缓释性好,抗肿瘤活性显著,可作为抗癌药物的缓释制剂。     

大蒜素/海藻酸钠/明胶/壳聚糖复合微球的制备及性能

以大蒜素为模型药物,采用复凝聚法制备了海藻酸钠/明胶/壳聚糖复合微球,考察了不同条件对微球溶胀性、载药性能和缓释性能等指标的影响。结果表明,明胶和海藻酸钠(质量比为1∶3)为2%,大蒜素投入量与混合胶比为1∶2时,制备的载药微球(DSGCM)外形规则,粒径分布在0.8~0.9mm之间,载药量为24.3%,包封率为69.4%,复合微球具有p H敏感性,在p H=7.4介质中微球溶胀率达到450%,药物释放过程符合Higuchi方程,明胶的加入可以延缓DSGCM复合微球的药物释放性能。     

蒙脱石微球的可控制备及其载药性能EI北大核心CSCD

针对口服给药体系如何保护药物分子免受人体内环境影响这一挑战,采用乳化凝胶法设计合成了一种pH值敏感性的海藻酸钠(SA)-蒙脱石(MMT)复合微球MMT/SA,用以负载抗癌药物盐酸阿霉素(DOX),在保护药物分子的同时克服了胃肠道的生物化学屏障。探索了MMT处理工艺和合成配比的不同对微球形貌的影响,最终控制微球尺寸在20μm以内,且分布均一。复合载药微球DOX/MMT/SA的载药率为14.7%,在模拟人工胃液和人工肠液环境中表现出不同的药物缓释效果,在模拟人工肠液中的累计释放率(31.7%)明显高于在人工胃液中的释放率(15.8%),且对人结肠癌细胞有明显的杀伤效果。     

负载丝裂霉素C的明胶多孔支架制备及释放

采用单乳化溶剂挥发法制备负载MMC的PLGA微球,通过相分离与冷冻干燥,制备含有载药微球的明胶多孔支架。支架的孔隙率达到90.2%,溶胀率为22.7%,压缩模量为52.1kPa。体外释放实验表明,载药微球中,MMC在5周的累计释放量为77.3%;支架中MMC的释放相对较缓,5周累积释放量为65.2%。这种含有载药微球的明胶复合多孔支架具有潜在的抗瘢痕应用前景。     

载阿霉素聚乳酸多孔微球的表征及释药性能

以阿霉素（DOX）为小分子化学药物模型,采用吸附法对聚乳酸（poly-L-lactide,PLLA）多孔微球进行载药,采用场发射扫描电子显微镜（FE-SEM）、傅里叶变换红外光谱（FTIR）、X射线衍射（XRPD）及差示扫描量热（DSC）对DOX-PLLA复合微球的形貌粒径及空气动力学性能、药物及材料的理化性能、载药性能进行表征,并且研究了其载药量、包封率和体外释放性能。结果表明,不同载药量之间的PLLA多孔微球粒径并无显著差异,均具有良好的空气动力学性能,适合肺部可吸入给药的条件;化学组成未见明显改变,物理结构由结晶态变为无定形态;随载药量的增加（2.9%,4.0%,4.6%）,包封率逐渐降低（56%,51%,44%）;药物的体外释放与原料药相比具有一定的缓释效果,最长释放时间可达5天,表明DOX-PLLA复合微球有望作为缓释制剂用于肺部给药。     

壳聚糖微球及壳聚糖-明胶复合物微球的制备及缓释性能研究

采用乳化-化学交联法制备壳聚糖微球及壳聚糖-明胶复合物微球,并通过实验确定了最佳的成球条件:即m(壳聚糖)∶m(明胶)=2∶1 span-80用量为10g/100 mL,乳化剪切速度为600 r/min,交联率为60％,固化时间为40min.该方法制备的壳聚糖微球球形圆滑,粘连度小,亲水性好.此外在对壳聚糖药物缓释的研究基础上,对壳聚糖复合明胶后,对药物缓释的影响情况进行了研究探索.以生物可降解性和生物相容性好的壳聚糖和明胶为载体承载阿司匹林,研制出阿司匹林壳聚糖-明胶微球,为阿司匹林提供了一种理想的缓释载体.     

氨苄西林磁性明胶药物微球的制备及控制释放

将药物封装入一个输送系统,以便在适当时间内持续控制药物释放.为此,利用明胶的生物相容性,选用难溶性氨苄西林(AMP)为药物模型,Fe3O4作为磁性内核,戊二醛作交联固化剂,液体石蜡为有机分散介质,采用反相悬液冷冻凝聚法(RPSCC)制备出了磁性AMP明胶核壳微球.用SEM、FT-IR和UV/Vis光谱等考察了药物微球的结构和外观形貌,以及药物在包封后的性质.结果表明磁性明胶药物微球的粒径小于20 μm.氨苄西林微球载药率(w/w)为7.1%,Fe3O4的含量为22.1%,微球包裹率为65.13%.7h内释放的药物占总含药量的72.3%.微球的缓释性能良好.     

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。     

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.     

Synthesis of collagen‐modified polylactide and its application in drug delivery

In this article, collagen modified polylactide (CPLA) was synthesized by means of graft modification, and its structure was confirmed by FTIR and FITC‐labeled fluorescence spectra. Subsequently, the performance of CPLA was characterized with hydrophilicity test and degradability test. After that, the aspirin sustained release microspheres of the synthetic copolymers were prepared via the emulsion‐solvent evaporation technique, followed with its measurements of morphology, size, and encapsulation efficiency. Finally, the controlled release properties of the obtained microspheres were investigated. The results showed that the aspirin sustained release microspheres exhibited well‐defined morphology with smooth spherical surface, with average size of 3.990 μm and encapsulation efficiency of 51.83%. Furthermore, compared with aspirin‐loaded PLA microspheres, at the initial 32 h, the drug release was faster for aspirin‐loaded CPLA microspheres favored by its increased hydrophilicity, and then the drug release was slower than that of PLA microspheres because the ? NH₂ group on the introduced collagen inhibited acidic autocatalytic degradation. The results suggested that CPLA showed a great potential as particles for drug delivery. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013     

APPLICATION OF GELATIN FOR ENCAPSULATING ASPIRIN INTO ETHYL CELLULOSE MICROCAPSULE IN AN O/W EMULSION

The application of gelatin protective colloid for microencapsulating aspirin in ethylcellulose was demonstrated using an oil-in-water emulsification/solvent evaporation technique. The gelatin concentration, alcohol co-solvent amount, and ethylcellulose viscosity were investigated by analyzing the recovered weight, particle size distribution, drug loading efficiency, aspirin release rate, surface characteristics, and release kinetics. Results showed that recovery increased with greater concentrations of gelatin (up to 1%). Adding co-solvent (ethanol) also changed the microcapsule particle size distribution. Higher recovery and release rates were obtained when the ethanol content in polymer solvent was at 25% and the viscosity of ethylcellulose was low (45cps). The release rate followed Higuchi matrix release kinetics, suggesting a monolithic system with aspirin uniformly distributed over the microcapsule.     

APPLICATION OF GELATIN FOR ENCAPSULATING ASPIRIN INTO ETHYL CELLULOSE MICROCAPSULE IN AN O/W EMULSION

The application of gelatin protective colloid for microencapsulating aspirin in ethylcellulose was demonstrated using an oil-in-water emulsification/solvent evaporation technique. The gelatin concentration, alcohol co-solvent amount, and ethylcellulose viscosity were investigated by analyzing the recovered weight, particle size distribution, drug loading efficiency, aspirin release rate, surface characteristics, and release kinetics. Results showed that recovery increased with greater concentrations of gelatin (up to 1%). Adding co-solvent (ethanol) also changed the microcapsule particle size distribution. Higher recovery and release rates were obtained when the ethanol content in polymer solvent was at 25% and the viscosity of ethylcellulose was low (45cps). The release rate followed Higuchi matrix release kinetics, suggesting a monolithic system with aspirin uniformly distributed over the microcapsule.     

Preparation of microspheres with microballoons inside for floating drug‐delivery systems

The use of floating drug‐delivery systems is one method that is used to achieve prolonged gastric residence times. We developed a novel, multiple‐unit, floating drug‐delivery system of microspheres with microballoons inside from xanthan gum (XG) and gelatin (GA) by a water‐in‐oil method. With theophylline as the model drug, four formulations (FI–FIV) with different ratios of the two polymers were prepared. The size distribution, drug‐encapsulation efficiency, floating behavior, release characteristics, and morphological properties were investigated. The ratio of the two polymers influenced the size distribution, encapsulation efficiency, and drug release appreciably. With increasing amounts of GA, the percentage yield of the floating microspheres and the drug‐encapsulation efficiency decreased from 100 and 84.5% to 31 and 56.2%, respectively. The drug‐release rate also decreased with increasing GA content, which was attributed to an increase in the crosslinking extent. An initial burst was observed, and after that, the drug was released slowly by a near‐zero‐order pattern, which was attributed to the low solubility of theophylline and the possible complexes formed by XG and GA in the simulated gastric fluid (pH 1.2). © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 94: 197–202, 2004     

Electrospun hydroxypropyl methyl cellulose phthalate (HPMCP)/erythromycin fibers for targeted release in intestine

Ultrafine fiber mats of hydroxypropyl methyl cellulose phthalate (HPMCP) were successfully electrospun and explored as drug delivery vehicles using erythromycin as a model drug. The morphology of the electrospun fiber and the drug release process in the artificial gastric juice and in the artificial intestinal juice were investigated. With the same drug‐to‐matrix ratio (HPMCP/erythromycin = 9/1), all the fibers were electrospun into a tape‐like or ribbon shape and the average fiber diameter (AFD) was increased with the HPMCP concentration. Because of the pH‐sensitive property of HPMCP, erythromycin was released from the erythromycin‐containing electrospun HPMCP fiber mats by a slowly diffusion process in the artificial gastric juice, while it was released in nearly first‐order kinetics in the artificial intestinal juice because of the first‐order kinetics dissolution of the HPMCP fibers in the artificial intestinal juice. And the rate of erythromycin released in the artificial intestinal juice was about more than 2.5 times faster than that in the artificial gastric juice. The diameter of the fibers plays an important role on the rate and the total amount of the drug released both in stomach and in intestine, the rate and the total amount of the drug released decreasing with increasing AFD. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 2007     

Preparation and evaluation of cellulose acetate butyrate and poly(ethylene oxide) blend microspheres for gastroretentive floating delivery of repaglinide

In this study, hollow microspheres of cellulose acetate butyrate (CAB) and poly(ethylene oxide) (PEO) were prepared by emulsion–solvent evaporation method. Repaglinide was successfully encapsulated into floating microspheres. Various formulations were prepared by varying the ratio of CAB and PEO, drug loading and concentration of poly(vinyl alcohol) (PVA) solution. Encapsulation of the drug up to 95% was achieved. The microspheres tend to float over the simulated gastric media for more than 10 h. The micromeritic properties of microspheres reveal the excellent flow and good packing properties. The % buoyancy of microspheres was found to be up to 87. SEM showed that microspheres have many pores on their surfaces. Particle size ranges from 159 to 601 μm. DSC and X‐RD revealed the amorphous dispersion in the polymer matrix. In vitro release experiments were performed in simulated gastric fluid. In vitro release studies indicated the dependence of release rate on the extent of drug loading and the amount of PEO in the microspheres; slow release was extended up to 12 h. The release data were fitted to an empirical equation to compute the diffusional exponent (n), which indicated that the release mechanism followed the non‐Fickian trend. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 2007     

快速膜乳化法制备载醋酸曲普瑞林PLGA微球

以生物可降解聚合物聚(乳酸?羟基乙酸)(PLGA)为载体,以160 g/L明胶水溶液为内水相、含500 g/L PLGA的二氯甲烷为油相,采用快速膜乳化和溶剂蒸发法制备了粒径均一的载醋酸曲普瑞林PLGA微球,微球粒径约30 mm,粒径分布系数Span<0.8,醋酸曲普瑞林包埋率达80.12%,药物在磷酸盐缓冲液中释放36 d的释放率为72.60%,体外释放行为良好.     

阿司匹林壳聚糖纳米缓释微球的制备及体外释放性能的研究

以自制阿司匹林为药物,壳聚糖为载体,采用乳化-化学交联法制备了阿司匹林-壳聚糖载药微球,确定了阿司匹林-壳聚糖载药微球的制备工艺条件,探讨搅拌速度、阿司匹林/壳聚糖质量比、交联剂戊二醛、乳化剂Span-80用量对微球的药物包封率、载药量和释药性能的影响。研究结果表明,室温条件下,以液体石蜡为介质,选用3%的壳聚糖冰醋酸溶液、按阿司匹林∶壳聚糖=1.5∶1、4%的戊二醛为交联剂、Span-80用量为体积比6%、中等搅拌速度制备出的微球药物包封率可达79%,微球粒径最小可达20 nm,制得的载药微球在16 h内对药物有良好的缓释作用,在25 h之内仍存在缓药效果。     

聚乳酸-羟基乙酸聚合物载入羟基喜树碱载药纳米粒子的制备及表征

以抗癌药物羟基喜树碱作为模型药物,可降解材料聚乳酸-羟基乙酸(PLGA)为药物负载体,采用溶剂-抗溶剂沉淀法制备聚乳酸-羟基乙酸/羟基喜树碱的载药纳米微球,考察不同溶剂-反溶剂体系对载药包封效果的影响。结果表明,以丙酮-水为溶剂体系制备的载药微球性能较好,形貌外观呈圆球形,球表面圆润光滑,粒度均一,分散效果良好,平均粒径为160 nm,载药微球包封率随着载药量的增加而减小,实测载药量为7.83%的PLGA载药微球,其载药包封率为87.68%,在28 d后溶出累计量约50%,可见以聚乳酸-羟基乙酸为载体制备的羟基喜树碱剂型,缓释作用良好。