Preparation and drug releasing property of magnetic chitosan-5-fluorouracil nano-particles

In order to synthesize the targeting drug carrier system,magnetic chitosan-5-fluorouracil nano-particles were prepared by using 5-fluorouracil(5-Fu)as model drug,Fe3O4 nano-particles as kernel,chitosan as enveloping material and glutaraldehyde as cross linking agent through ultrasonic technique.The morphology of the magnetic chitosan-5-Fu nano-particles was observed with a transmission electron microscope(TEM).The results showed that magnetic chitosan-5-Fu nano-particles were prepared in spherical structure with a size range of 50-60 nm.The delivering capacity and drug releasing properties of magnetic chitosan-5-Fu nano-particles were investigated by UV-vis spectrum analysis.The results showed that the loading capacity was 13.4%and the cumulative release percentage in the phosphate buffer(pH=7.2)solutions was 68%in 30 h.These data indicate that the wrapped drug of magnetic chitosan-5-Fu nano-particles was slowly-released.The magnetic response of magnetic chitosan-5-Fu nano-particles was studied by UV-vis spectrometer to detect the changes of solution absorbance.Without external magnetic field,the nano-particle deposition rate was slow.When being subjected to 8 mT magnetic field,the particle sedimentation rate was increased rapidly.The results showed that magnetic chitosan-5-Fu nano-particles have a magnetic stability and strong targeting characteristics.

Preparation and Properties of Gelatin-Chitosan/Montmorillonite Drug-loaded Microspheres

A kind of slow release drug-loaded microspheres were prepared with gelatin, chitosan and montmorillonite（MMT） by an emulsification/chemical cross-linking method using glutaraldehyde as cross-linking agent and acyclovir as model drug. The microspheres were characterized by X-ray diffraction （XRD）, Fourier transform infrared （FT-IR） and scanning electron microscopy （SEM）, respectively. The morphology, drug content, encapsulation efficiency and drug-release behavior were investigated with different MMT contents. The experimental results indicated that intercalated microspheres could be prepared, the morphology of microspheres was markedly affected by MMT. The glomeration performance of uncross-linked microspheres was improved because of the physical cross-linking of MMT. Drug content and encapsulation efficiency were decreased when increased the content of MMT, but burst release and the drug release were significantly decreased with the addition of MMT. Effective physical cross-linking could be formed when added MMT, and MMT could reduce the content of toxic chemical cross-linking agents.

5-Fluorouracil Loaded Chitosan–PVA/Na^+MMT Nanocomposite Films for Drug Release and Antimicrobial Activity

In the present study, chitosan and polyvinyl alcohol(PVA) were blended with different concentrations of sodium montmorillonite(Na^+MMT) clay solution by a solvent casting method. X-ray diffraction and transition electron microscope results show that the film properties are related to the co-existence of Na^+MMT intercalation/exfoliation in the blend and the interaction between chitosan–PVA and Na^+MMT. 5-Fluorouracil(5-FU) was loaded with chitosan–PVA/Na^+MMT nanocomposite films for in vitro drug delivery study. The antimicrobial activity of the chitosan–PVA/Na^+MMT films showed significant effect against Salmonella(Gram-negative) and Staphylococcus aureus(Gram-positive), whereas5-FU encapsulated chitosan–PVA/Na^+MMT bio-nanocomposite films did not show any inhibition against bacteria. Our results indicate that combination of a flexible and soft polymeric material with high drug loading ability of a hard inorganic porous material can produce improved control over degradation and drug release. It will be an economically viable method for preparation of advanced drug delivery vehicles and biodegradable implants or scaffolds.

Preparation and in vitro Release Performance of Sustained-release Captopril/Chitosan-gelatin Net-polymer Microspheres

The captopril/Chitosan-gelatin net-polymer microspheres(CTP/CGNPMs) were prepared using Chitosan(CTS) and gelatin(GT) by the methods of emulsification,cross-linked reagent alone or in combination and microcrystalline cellulose(MCC) added in the process of preparation of microspheres,which aimed to eliminate dose dumping and burst phenomenon of microspheres for the improvement of the therapeutic efficiency and the decrease of the side effects of captopril(CTP). The results indicated that CTP/CGNPMs had a spherical shape,smooth surface and integral structure inside but no adhesive phenomena in the preparation. The size distribution ranged from 220 μm to 280 μm. The CTP release test in vitro demonstrated that CTP/CGNPMs played the role of retarding the release of CTP compared with ordinary CTP tablets. The release behaviors of CGNPMS were influenced by preparation conditions such as experimental material ratio(EMR) and composition of cross linking reagents. Among these factors,the EMR(1/4),CLR(FA+SPP) and 0.75% microcrystalline cellulose(MCC) added to the microspheres constituted the optimal scheme for the preparation of CTP/CGNPMs. The ER,DL and SR of CTP/CGNPMs prepared according to the optimal scheme were 46.23±4.51%,9.95±0.77% and 261±42%,respectively. The CTP/CGNPMs had the good characteristics of sustained release of drug and the process of emulsification and cross-linking were simple and stable. The CGNPMs are likely to be an ideal sustained release formulation for water-soluble drugs.

Preparation and Characterization in vitro of Sustained-release Captopril/ Chitosan-gelatin Net-polymer Microspheres(Cap/CGNPMs)

The captopril/ Chitosan-gelatin net-polymer microspheres （ Gap/ CGNPMs ） were prepared using Chitosan （ CS ） and gelatin （ Gel ） by the methods of emulsification. A cross linked reagent alone or in combination with microcrystalline cellulose （ MCC ） was added in the process of preparation of microspheres to eliminate dose dumping and burst phenomenon of microspheres for the improvemeat of the therapeutic efficiency and the decrease of the side effects of captopril （ Cap ）. The results indicate that Cap/ CGNPMs have a spherical shape , smooth surface roorphology and integral inside structure and no adhesive phenomena and good roobility , and the size distribution is mairdy from 220 to 280 μm. Researches on the Cap release test in vitro demonstrate that Cap/ CGNPMs are of the role of retarding release of Cap compared with Cap ordinary tablets （COT）, embedding ratio （ER） , drug loading （ DL ）, and swelling ratio （ SR ）, and release behaviors of CGNPMS are influenced by process conditions of preparation such as experimental material ratio （EMR） , composition of cross linking reagents. Among these factors , the EMR（1/4）, CLR （ FOR ＋ TPP） and 0.75% microcrystulline cellulose （MCC） added to the microspheres are the optimal scheme to the preparation of Cap/CGNPMs. The Cap/CGNPMs have a good characteristic of sustained release of drug, and the process of emulsifieation and crossinking process is simple and stable. The CGNPMs is probable to be one of an ideal sustained release system for water-soluble drugs.

5-氟尿嘧啶壳聚糖微球的制备及其释药性能

以壳聚糖为载体 ,戊二醛为交联剂 ,以span 80和硬脂酸镁为复合乳化剂 ,真空泵油和石蜡油相混合为油相 ,通过乳液 化学交联法制备了 5 氟尿嘧啶壳聚糖微球 ,所得微球的药物包封率可达 43 6%～ 84 8% ,比文献报道的 (约 1 5 1 % )高 2～ 4倍。在Na2 HPO4 KH2 PO4缓冲溶液 (pH =7 4)和柠檬酸钠 盐酸缓冲溶液 (pH=3 9)中进行的药物释放实验表明 ,5 氟尿嘧啶与壳聚糖的质量投料比 ,戊二醛用量及释药介质的pH值均对微球的释药速率产生影响 :随着m( 5 Fu) /m(CS)比的减小 ,微球的释药速率减慢 ;随着n(CHO) /n(NH2 )比的增大 ,微球的释药速率减慢 ;在酸性条件下的缓释效果更好。IR和SEM对微球进行的结构表征和形态观察表明 ,壳聚糖与 5 氟尿嘧啶之间有比较强的分子间作用力 ,微球球形规整 ,分散性好 ,粒径分布在 1～ 5 μm之间。

磁性壳聚糖微球的制备、表征及其靶向给药研究

质量分数为 1 0 %的壳聚糖溶液通过乳液法与戊二醛交联合成了壳聚糖微球 ( CM) ,在其表面吸附一层 Fe3 O4制得磁性壳聚糖微球 ( MCM)。用扫描电镜、红外光谱仪、原子吸收分光光度计和紫外吸收分光光度计对合成的高分子微球进行了形貌观察和结构表征。结果表明 ,降低壳聚糖的分子量 ,有利于合成单分散性好、粒径小 ( <1 μm)的微球 ;体外测试表明 ,CM包封阿斯匹林 ( AS)微球 ( CM-AS)在 1 h内释药量达 4 0 % ,而MCM-AS仅为 1 5 % ,CM-AS和 MCM-AS释药量达 5 0 %的时间分别为 1 .4和 5 h;MCM和 MCM-AS均具有较强的磁性 ,后者在外磁场作用下能够实现靶向给药。

5-氟脲嘧啶壳聚糖微球的制备及体外释放特性

目的 :以壳聚糖为载体材料 ,5 氟脲嘧啶为模型药物 ,制备鼻腔给药脑靶向微球并考察其体外释放。方法 :采用乳化化学交联法制备氟脲嘧啶鼻用微球 ,正交实验设计中引入理想函数优化制备工艺 ,扫描电镜观察微球表面形态 ,动态透析法检测微球的体外释放特性及其影响因素。用微球吸水能力表示微球的溶胀度。结果 :所得微球形态良好 ,粒径分布窄 ,平均粒径为 4 3 2 0± 4 17μm ,载药量为 (38 4 8± 1 0 3) % ,包封率为 (78 96± 1 77) %。体外释放符合Higuichi方程Q =0 10 35t1/2 +0 0 2 84 ,r=0 996 5。体外释放初始阶段释药快 ,遵守溶胀控制机理 ,释放后期释药减慢 ,遵守扩散控制机理。结论 :所优化的制备工艺稳定 ,包封率较高 ,适于鼻粘膜用氟脲嘧啶壳聚糖微球的制备。

鼻用氟尿嘧啶壳聚糖微球的制备及其特性研究

目的 :以壳聚糖为载体材料 ,氟尿嘧啶为模型药物 ,制备鼻腔给药脑靶向微球。方法 :以液体石蜡为油相 ,span 80为乳化剂 ,采用乳化化学交联技术制备氟尿嘧啶鼻用微球。正交实验设计优化制备工艺 ,动态透析法检测微球的体外释放特性及其影响因素。用微球吸水能力表示微球的溶胀度。测定纤毛输送速率来评价微球的黏膜粘附力。结果 :所得微球形态良好 ,粒径分布较为均匀 ,平均粒径 (4 3± 4 ) μm ,载药量 38.5 %± 1.0 % ,包封率 79.0 %± 1.8%。体外释放符合Higuichi方程Q =0 .10 35t1/ 2 +0 .0 2 84 (r =0 .996 5 )。壳聚糖微球具有良好的生物粘附性 ,可显著降低纤毛输送速率 (P <0 .0 1) ,有效地延长微球在鼻腔的滞留时间。结论 :所优化的制备工艺稳定 ,包封率较高 ,适于鼻黏膜用氟尿嘧啶壳聚糖微球的制备。壳聚糖是良好的鼻用制剂的载体材料 ,应用前景广阔。

生物相容壳聚糖/蒙脱土复合微球的溶胀与药物缓释性能研究

利用反相乳液聚合法制备出具有良好生物相容性的壳聚糖/蒙脱土复合微球,其中改性蒙脱土作为插层改性剂引入。用X射线衍射和红外光谱分析了改性蒙脱土的结构,以阿司匹林为模型药物,以药物包埋法制备出了壳聚糖/蒙脱土载药微球,并对其缓释性能进行探讨。结果表明,改性蒙脱土的层间距变大,随着蒙脱土含量的增大,复合微球的溶胀率降低,释药率逐渐减小,pH值为1.2下的壳聚糖/蒙脱土载药微球的释药模式为Fickian扩散类型,pH值为7.4下的释药模式为non-Fickian扩散,壳聚糖/蒙脱土复合微球作为药物载体很有潜力。

磁性壳聚糖-5-氟尿嘧啶纳米粒的制备及体外释药性能

采用交联-聚合法在超声波的作用下,制备了磁性壳聚糖-5-氟尿嘧啶纳米粒(M CN-Fu)。透射电子显微镜(TEM)和红外光谱(IR)等分析结果表明,M CN-Fu粒子外形规整,分散性好,粒径主要在50 nm^60 nm之间。紫外-可见光谱分析结果表明,M CN-Fu的载药量为21.3%,在磷酸盐缓冲溶液(pH=7.2)中,30 h的累积释药率为67.6%,具有良好缓释性能,并具有良好磁响应性能。

鼻用氟脲嘧啶壳聚糖微球的体外释放及溶胀影响因素

目的考察壳聚糖脱乙酰度、壳聚糖浓度、固化剂用量、固化时间以及介质pH值对氟脲嘧啶壳聚糖微球的体外释放与溶胀的影响。方法乳化化学交联法制备氟脲嘧啶鼻用微球,动态透析法检测微球的体外释放特性;根据微球吸水前后质量变化测定微球的溶胀率。结果壳聚糖的脱乙酰度越高、固化剂用量越大、固化时间越长则微球的溶胀越慢,微球的体外释放越慢;壳聚糖浓度的增加则使微球的溶胀度增加,体外释放量减少;释放介质的pH值对微球的溶胀性能影响很大,在酸性条件下微球溶胀度高且释药加快。结论影响壳聚糖微球溶胀的因素顺序为介质的pH值>固化剂用量>固化时间>壳聚糖浓度≈壳聚糖脱乙酰度;影响壳聚糖微球体外释放的因素顺序为固化剂用量>壳聚糖脱乙酰度>壳聚糖浓度,而固化时间和介质的pH值对体外释放无显著性影响。

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。

金雀异黄素/壳聚糖微球的制备及其释药性能

制备了金雀异黄素／壳聚糖微球，考察了其理化性质和药物的缓释性能．结果表明，微球形状较规整，平均粒径2～4μm，载药质量分数为10．5％，药物包封率达质量分数52．5％．金雀异黄素以无定形聚集态分散在微球内部．微球中的药物缓释效果好，而释药速率随投料比（药物／壳聚糖）增加和反应介质pH增大而增大．药物在酸性缓冲环境中的释药速率大．

替莫唑胺壳聚糖缓释微球的制备及体外释药特性

目的:制备替莫唑胺壳聚糖缓释微球,并对其体外释药模式进行研究.方法:以替莫唑胺为模型药物,采用乳化交联法制备壳聚糖微球,两步优化法优化处方和制备工艺.通过测定微球的粒径及其分布、载药量、包封率和体外释放速度对微球进行质量评价.结果:优化工艺制得的微球平均粒径为(3.9±1.6)μm,载药量为(7.1±0.5)%(n=3),包封率为(25.0±0.8)%(n=3),体外释药特性研究具有良好的缓释特性,在0～8 h符合Higuchi方程,Q=11.717+26.951t1/2(r=0.980),8～24 h符合一级释放曲线,lnQ=4.37+0.007 5t(r=0.983).结论:通过优化处方和制备工艺,采用乳化交联法可制备出以壳聚糖为载体、替莫唑胺为模型药物的缓释微球,其体外释药具有明显的缓释作用.

紫杉醇壳聚糖纳米微球的制备及体外释放性能

目的：优化试验条件，制备合适的壳聚糖纳米微球（CM），并负载紫杉醇（PTX），研究负载紫杉醇壳聚糖微球（PTX-CM）的体外释药性能。方法：采用离子凝聚法和透析法制备CM及PTX-CM，激光粒度分析仪测定微球粒径大小和分布，透射电镜观测微球形态学特征，并在磷酸盐缓冲液（PBS，pH7．4）中对PTX-CM进行体外释药研究。结果：制备CM的最佳条件是壳聚糖（CTS）与多聚磷酸钠（TPP）投量比在3：1～6：1间。制备的PTX-CM形态规则均质，无粘连，平均粒径179．3nm，包封率80．0％，载药量20．6％，在8d内累积释药率接近80．0％。结论：PTX-CM性能良好，制备工艺简单，有望成为理想的紫杉醇缓释系统。

生物可降解5-氟尿嘧啶载药微球的制备及性能研究

Microspheres containing an antimetabolite drug 5-Fluorouracil were prepared from (poly(lactic) acide)(PLA) or poly(lactic acid)-polyethylene glycol(PLA-PEG) as the carrier by using a water-in-oil-in-water emulsion solvent evaporation technique. The conditions of the microspheres preparation such as polymer concentration in organic solvent, relative molecular weight of PLA-PEG and PLA/PEG mass ratio were discussed. The surface morphology and the size of the microspheres were observed by SEM. The drug content of microspheres was examined by TGA and the drug release in vitro was evaluated. According to the results, the drug content increased with the nano-silica used. The highest drug content in this study was 39.9%. The drug-release kinetics satisfied the requirements of controlled drug-release.

磁性氟尿嘧啶壳聚糖微球的制备及其释药性能

采用乳液-化学交联法制备磁性氟尿嘧啶壳聚糖微球，重铬酸钾法测定磁性微球中铁含量，古埃磁天平测定磁性微球的磁化率，用SEM测试技术观察了微球的形态；考察了磁性氟尿嘧啶壳聚糖微球在磷酸盐缓冲溶液中的释药性能。结果表明，磁性氟尿嘧啶壳聚糖微球具有强顺磁性，粒径分布1～10μm，Fe3O4质量分数为4．55％～11．44％，药物质量分数为1．86％～9．42％，药物包封率为39．48％～85．30％。体外药物释放实验表明，对氟尿嘧啶的缓释作用明显，释放周期比较长，Fe3O4粒子和含量对微球的释药速率影响不明显；药物释放主要受扩散机制控制，药物含量越大，药物从微球中释放出来的速率越快，可作为理想的磁靶向药物控释体系。

胰岛素-壳聚糖缓释微球释药机制的研究

目的:研制具有良好缓释效果的胰岛素微球,并研究胰岛索-壳聚糖微球的释药机制。方法:用乳化交联技术制备 了胰岛素微球,并对胰岛素-壳聚糖缓释微球缓释机制进行了初步探讨。结果:该微球具有良好缓释效果。结论:胰岛素-壳聚 糖微球的释药机制为药物的突释效应、亚胺键的水解、壳聚糖的吸水膨胀以及药物通过胶状黏稠层向外扩散等几个相互衔接 的步骤。

5-氟尿嘧啶/壳聚糖载药纳米微球的制备及性能

以三聚磷酸钠为交联剂,采用离子交联法制备了5-氟尿嘧啶/壳聚糖纳米微球,评价其性能、体外释药性能及对人肺癌细胞GLC-82的体外杀伤效应,并通过Zeta电位和红外光谱分析载药纳米微球形成机理。结果表明,所制备的5-Fu/CS纳米微球平均包封率为32.3%,平均载药量为25.6%,平均粒径为253nm,平均Zeta电势为+8.38mV,成球性及分散性良好。CS载药纳米微球具有缓释性能,体外释药行为符合双向动力学规律。在体外作用72h,CS载药纳米微球对人肺癌细胞GLC-82的杀伤率达66.6%,杀伤效果明显优于5-Fu对照组。