海藻酸钙/聚精氨酸微胶囊的制备及其生物相容性

以海藻酸盐、 聚精氨酸为壁材, 采用高压静电法制备了球形度好、 表面光洁、 粒径均匀的新型药物载体——海藻酸钙/聚精氨酸微胶囊。参照医疗器械生物学评价标准, 对其生物相容性进行了研究。细胞毒性试验结果显示, 当海藻酸钙/聚精氨酸微胶囊的含量为0.1、 0.5、 1.0 mg/mL时, 微胶囊对L929细胞生长无明显抑制作用, 海藻酸钙/聚精氨酸微胶囊浸提产物在10.0 mg/mL时仍无细胞毒性作用。海藻酸钙/聚精氨酸微胶囊不引起急性全身毒性反应, 不引起溶血反应。通过本组试验可见, 采用高压静电法制备的药物载体——海藻酸钙/聚精氨酸微胶囊具有较好的生物相容性, 具有开发和应用价值。     

栓塞型载卡培他滨微胶囊的性能

以生物相容性好且可生物降解的海藻酸钠(Sodium Alginate, Alg)、几丁聚糖(Chitosan, Chi)为壁材, 采用静电液滴装置制备了球形度好、表面光洁、分散性好、平均粒径为210 μm的海藻酸钙(Calcium Alginate, Ca-Alg)胶珠, 并以卡培他滨(CAP)为模型药物, 采用一步法和两步法制备了栓塞型载CAP Ca-Alg/Chi微胶囊, 并考察了CAP浓度对微胶囊载药量和药物释放的影响。结果表明: 随着CAP浓度的增大, 载药量增大, 包封率却随之减小; 微胶囊在0.5 h内的累积释放量不到20%, 无突释效应; 微胶囊有一定的缓释性能, 有望成为一种栓塞型抗肿瘤药物新剂型。      

海藻酸钙-几丁聚糖微胶囊的形态与粒径

以静电法通过高压成型装置制备了海藻酸钙-几丁聚糖微胶囊,重点考察了海藻酸钠浓度、凝胶化时间、成膜前冲洗液的种类、几丁聚糖溶液的pH值对微囊形态与粒径的影响.实验结果表明,与生理盐水、甘露醇及直接成膜相比,成膜前采用蒸馏水冲洗胶珠制备出的微囊大小均匀、表面光洁、球形度好;几丁聚糖溶液pH值对微囊形态,甚至膜强度有很大的影响,应根据实际应用需要选取适当的pH值,初步探讨了微囊的控制释放性能.     

海藻酸钠/硫酸鱼精蛋白载药微胶囊的制备及缓释性能

直接以疏水性药物吲哚美辛微晶为模板,采用层层自组装技术,通过静电作用将聚阳电解质硫酸鱼精蛋白(PRM)和聚阴电解质海藻酸钠(ALG)交替沉积制备载药微胶囊。利用扫描电镜对其形貌进行表征,并采用紫外分光光度计考察了组装层数、释放介质的温度、离子强度、p H值等因素对其缓释性能的影响。结果表明,采用层层自组装方法可以得到(ALG/PRM)n@IDM载药微胶囊,该微胶囊对药物有显著的缓释作用,并且增加组装层数、提高释放介质的盐浓度、降低释放介质的p H值及温度均可以降低药物的释放速率。     

海藻酸钙/环氧微胶囊在水泥基材料中的自修复作用

采用锐孔-凝固浴法制备海藻酸钙/环氧树脂复合微胶囊,将其应用于水泥基自修复材料。表征了微胶囊的微结构、力学强度和吸水溶胀等性能,并通过X射线计算机断层扫描技术和SEM/EDS分析微胶囊在水泥基材料中的修复作用机制。结果表明:制备的海藻酸钙微胶囊为三维网络支架结构;在粒径为0.7~2 mm,粒径尺寸不影响微胶囊的强度;海藻酸钙含量决定微胶囊的强度、吸水率和溶胀率。海藻酸钙/环氧微胶囊的裂缝修复机制为:基体产生裂缝,微胶囊发生破裂释放环氧树脂,粘结裂缝;裂缝中有水渗入时,微胶囊吸水溶胀,堵塞裂缝,进而促进周围水泥颗粒的继续水化,修复裂缝。     

PSY-g-PAA/APT/SA载药复合凝胶小球的制备及释药性能

采用离子凝胶法制备了欧车前胶-g-聚丙烯酸/凹凸棒黏土/海藻酸钠(PSY-g-PAA/APT/SA)载药复合凝胶小球,以双氯芬酸钠为模型药物,考察了pH敏感性和凹凸棒黏土含量对凝胶小球的包封率、载药率、溶胀性能和药物释放行为的影响。结果表明,当释放介质为模拟胃液(pH=1.2)时,药物基本不释放;而为模拟肠液(pH=6.8)时,5h后累积释放率超过90%,复合凝胶小球具有明显的pH敏感性。随着凝胶小球中凹凸棒黏土含量的增加,溶胀率和药物累积释放率均减小,表明凹凸棒黏土的引入可以减缓药物的突释效应。     

广藿香油缓释微胶囊的制备及其性能分析

以广藿香油为芯材,壳聚糖和阿拉伯胶为壁材,采用复凝聚法对广藿香油进行包埋,制备广藿香油微胶囊。利用扫描电子显微镜、激光粒度仪、红外光谱和紫外光谱等分析方法研究各因素对微胶囊形成的影响。确定制备广藿香油微胶囊的最佳条件:采用中低粘度的壳聚糖,壳聚糖浓度为0.5%,阿拉伯胶浓度为4%,芯壁比为1∶2,复凝聚pH值为4.5,搅拌转速为2000r/min。红外光谱分析表明广藿香油包埋成功,其载药量和包封率分别为20.75%和67.2%。微胶囊缓释性能测试结果表明微胶囊具有良好的缓释效果,在25℃条件下,微胶囊释放150h后,累计释放率为33%,即微胶囊保留率为67%。     

毫米级海藻酸钙水胶囊的可控制备及其缓释性能

以海藻酸钙为壁材,羧甲基纤维素钠水溶液为芯材,采用锐孔凝固浴法制备了毫米级海藻酸钙水胶囊,通过Duncan’s test和正交试验考察了海藻酸钠浓度,CaCl_2浓度及芯壁溶液流速比对胶囊形貌、粒径、膜厚、力学性能和缓释性能的影响。结果表明,可制备具有较好圆整度和薄壁结构的海藻酸钙水胶囊,胶囊粒径随着海藻酸钠浓度的升高而减小,随着CaCl_2浓度和芯壁流速比的升高而增大,其中芯壁流速比的影响最显著,胶囊粒径在3~4mm之间可调;压碎强度随着囊膜厚度及交联程度的增大而提高;同时,胶囊内的活性红B4BD在水溶液中的释放过程遵循一级释放动力学方程。毫米级海藻酸钙水胶囊在食品、医药、卫生及纺织等领域具有良好的应用前景。     

海藻酸钙-聚精氨酸聚电解质微胶囊强度性能研究

制备了一种新型的聚精氨酸基微胶囊并考察了制备条件对微胶囊机械强度性能的影响,以期望制备一种具有介入治疗效果的药物载体.实验采用高压静电液滴发生装置,所制备的微胶囊粒度均匀、球形度好.同时,海藻酸钠浓度、成膜时间以及聚精氨酸分子量对微囊膜的机械强度有不同程度的影响.当海藻酸钠浓度为1.0%,成膜时间高于15min,聚精氨酸分子量为55,300和141,000μ时,膜机械强度最好.此外,实验初步考察了聚电解质络合反应机理.结果表明,通过改变实验条件,可有效地控制微囊膜的膜强度,从而为进一步的药物控制释放实验打下一定的基础.     

海藻酸钠-壳聚糖-粉末活性炭生物微胶囊的制备

制备了海藻酸钠-壳聚糖-粉末活性炭(SA-CA-PAC)微胶囊,研究了添加适量粉末活性炭后对新型SA-CA-PAC生物微胶囊的粒径、机械强度和膨胀度等主要性能的影响.结果表明:适量粉末活性炭的添加对海藻酸钙胶珠和SA-CA-PAC微胶囊其它制备条件的影响不大,但却对SA-CA-PAC微胶囊的机械强度性能有较大的影响.在反应温度为30℃时,向2.0%的海藻酸钠溶液中添加粉末活性炭量为0.75%,氯化钙溶液浓度为4.0%,壳聚糖溶液浓度1.8%,成膜反应时间10 min,覆膜时间10 min,液化时间8 min,控制盐离子浓度为1.5%,所制得的SA-CA-PAC微胶囊具有良好的成囊性能.扫描电镜结果显示,SA-CA-PAC微胶囊具有良好的膜结构.     

Drug release behaviors of a pH/temperature sensitive core-shelled bead with alginate and poly(N-acryloyl glycinates)

In this study, a pH/temperature sensitive bead with core-shelled structure, as a drug carrier, was prepared by grafting of N-acryloylglycinates on the surface of sodium alginate beads. The pH and temperature sensitivity of the beads originate from sodium alginate (SA) and copoly(N-acryloylglycinates), respectively. Here, indomethacin (IMC) was selected as a drug model molecule and loaded in SA beads. The release of IMC was systematically investigated as a function of temperature, pH, and SA concentration. The amount of IMC released from beads was as high as 61.6%in pH = 7.4 phosphate buffer solution (PBS) over 620 min, whereas only 27.9% IMC diffused into the pH = 2.1 PBS. In addition, the release rates of IMC at 37.5°C were faster than that at 20.0°C and decreased with increasing SA concentration in the beads. The result indicates that the sensitive beads have the potential to be used as an effective pH/temperature-controlled delivery system in the biomedical fields.     

Drug release behaviors of a pH/temperature sensitive core-shelled bead with alginate and poly(<Emphasis Type="Italic">N</Emphasis>-acryloyl glycinates)

In this study, a pH/temperature sensitive bead with core-shelled structure, as a drug carrier, was prepared by grafting of N-acryloylglycinates on the surface of sodium alginate beads. The pH and temperature sensitivity of the beads originate from sodium alginate (SA) and copoly(N-acryloylglycinates), respectively. Here, indomethacin (IMC) was selected as a drug model molecule and loaded in SA beads. The release of IMC was systematically investigated as a function of temperature, pH, and SA concentration. The amount of IMC released from beads was as high as 61.6%in pH = 7.4 phosphate buffer solution (PBS) over 620 min, whereas only 27.9% IMC diffused into the pH = 2.1 PBS. In addition, the release rates of IMC at 37.5°C were faster than that at 20.0°C and decreased with increasing SA concentration in the beads. The result indicates that the sensitive beads have the potential to be used as an effective pH/temperature-controlled delivery system in the biomedical fields.     

聚乳酸/杆菌肽静电纺丝纤维的体外释药研究

为探讨聚乳酸纤维结构形貌对杆菌肽药物的缓慢释放行为及作用机理,通过静电纺丝法制备了聚乳酸/杆菌肽单轴纤维、聚乳酸/杆菌肽串珠和(聚乳酸/杆菌肽)-聚乳酸同轴核-壳纤维等聚乳酸/杆菌肽药物缓释体系,并采用红外光谱法和差热分析法对其化学结构和热性能进行了表征.利用紫外分光光度计法研究了不同载药体系的体外药物释放行为,并探索了不同降解时期载药纤维的质量和形貌变化规律.研究表明:杆菌肽与聚乳酸主要为物理结合;聚乳酸单轴纤维和串珠对杆菌肽的扩散释放机理,属于纯Fick扩散;采用单轴和同轴静电纺丝技术可以获得两种不同释药特性的载药纤维.单轴纤维和串珠能够将药物快速释放,适合抗生素的治疗;同轴纤维中药物受控释放,更适合长期、小剂量的药物释放.     

Colonic drug delivery: influence of cross-linking agent on pectin beads properties and role of the shell capsule type

For colonic delivery, pectin beads obtained by ionotropic gelation method have been already reported as an interesting approach. This study investigated the influence of the cross-linking agent (calcium or zinc) and the type of shell capsule used (classical or enteric capsules) on pectin beads properties and on their performance to target the colon (in vitro dissolution studies with subsequent pH change to mimic overall gastro-intestinal tract). Zinc pectinate beads seemed to be relatively similar to calcium's ones in morphological point, except on the surface aspect. When beads were introduced in classical hard capsules, ketoprofen release was not significantly different between CPG and ZPG beads, and it was too premature and too quick due to a chemical erosion of the pectinate matrix (acid + basic attacks). However, zinc pectinate beads showed slower ketoprofen release compared with calcium pectinate beads when enteric hard capsules were used. This interesting finding could be due to the strength of the network formed during the process between the zinc cations and the LM-pectin following the “egg-box” model. This network was stronger and induced a reduction of swelling and hydration when contact with dissolution medium, then subsequently a decrease of drug release. Thus, the zinc pectinate beads could protect sufficiently drug entrapped from the upper gastro-intestinal conditions and drug release will be controlled by pectin degradation with colonic microflora. Finally, these zinc pectinate beads in enteric hard capsules are promising as a carrier for specific colonic delivery of drugs after oral administration.     

Colonic Drug Delivery: Influence of Cross-linking Agent on Pectin Beads Properties and Role of the Shell Capsule type

ABSTRACT

For colonic delivery, pectin beads obtained by ionotropic gelation method have been already reported as an interesting approach. This study investigated the influence of the cross-linking agent (calcium or zinc) and the type of shell capsule used (classical or enteric capsules) on pectin beads properties and on their performance to target the colon (in vitro dissolution studies with subsequent pH change to mimic overall gastro-intestinal tract). Zinc pectinate beads seemed to be relatively similar to calcium's ones in morphological point, except on the surface aspect. When beads were introduced in classical hard capsules, ketoprofen release was not significantly different between CPG and ZPG beads, and it was too premature and too quick due to a chemical erosion of the pectinate matrix (acid + basic attacks). However, zinc pectinate beads showed slower ketoprofen release compared with calcium pectinate beads when enteric hard capsules were used. This interesting finding could be due to the strength of the network formed during the process between the zinc cations and the LM-pectin following the “egg-box” model. This network was stronger and induced a reduction of swelling and hydration when contact with dissolution medium, then subsequently a decrease of drug release. Thus, the zinc pectinate beads could protect sufficiently drug entrapped from the upper gastro-intestinal conditions and drug release will be controlled by pectin degradation with colonic microflora. Finally, these zinc pectinate beads in enteric hard capsules are promising as a carrier for specific colonic delivery of drugs after oral administration.     

Preparation and characterization of magnetic alginate-chitosan hydrogel beads loaded matrine

The aim of this study was to use alginate-chitosan (Alg-CS) hydrogel beads for developing an oral water-soluble drug delivery system, occupying pH-sensitive property and superparamagnetic. Matrine as a model drug was loaded in Alg-CS hydrogel beads to study the release character of the delivery system. The amount of matrine released from the beads was relatively low in pH 2.5 over 8?h (34.90%), but nearly all of the initial drug content was released in simulated intestinal fluid (SIF, pH 6.8) within 8?h. The results demonstrated that Alg-CS hydrogel beads possess unique pH-dependent swelling behaviors. In addition, the magnetic beads were characterized by Fourier transform infrared spectroscopy, scanning electron microscope, X-ray diffractometry and vibrating-sample magnetometry. Magnetometer measurements data suggested that Alg-CS beads also had superparamagnetic property as well as fast magnetic response. It can be expected that the beads can deliver and release encapsulated anticancer agent at the tumor by the weak magnetic field, and hence could be potential candidates as an orally administered drug delivery system.     

Preparation and characterization of magnetic alginate-chitosan hydrogel beads loaded matrine

The aim of this study was to use alginate-chitosan (Alg-CS) hydrogel beads for developing an oral water-soluble drug delivery system, occupying pH-sensitive property and superparamagnetic. Matrine as a model drug was loaded in Alg-CS hydrogel beads to study the release character of the delivery system. The amount of matrine released from the beads was relatively low in pH 2.5 over 8?h (34.90%), but nearly all of the initial drug content was released in simulated intestinal fluid (SIF, pH 6.8) within 8?h. The results demonstrated that Alg-CS hydrogel beads possess unique pH-dependent swelling behaviors. In addition, the magnetic beads were characterized by Fourier transform infrared spectroscopy, scanning electron microscope, X-ray diffractometry and vibrating-sample magnetometry. Magnetometer measurements data suggested that Alg-CS beads also had superparamagnetic property as well as fast magnetic response. It can be expected that the beads can deliver and release encapsulated anticancer agent at the tumor by the weak magnetic field, and hence could be potential candidates as an orally administered drug delivery system.     

Study of Formulation Variables on Properties of Drug-Gellan Beads by Factorial Design

ABSTRACT

The aim of the present study was to obtain cross-linked calcium-gellan beads containing diclofenac sodium as model drug, using full 3³ factorial design. Drug quantity, pH of cross-linking solution, and speed of agitation were selected as variables for factorial design. The resultant beads were evaluated by scanning electron microscopy (SEM), percent yield, entrapment efficiency, micromeritic properties, swelling and drug release studies. The drug-loaded beads were spherical with size range of 0.85–1.8 mm. Percent yield and entrapment efficiency of various batches were in the range of 86.48–98.28% w/w and 72.52–92.74% w/w, respectively. Calcium-gellan beads containing diclofenac sodium showed pH-dependent swelling and drug release properties. Swelling and drug release were significantly higher in pH 7.4 phosphate buffer than 0.1N HCl. The swelling ratio for beads was up to 22 and 3 for phosphate buffer and 0.1N HCl, respectively. Cumulative diclofenac sodium release from calcium-gellan beads was 12–35% in 0.1N HCl within 2 h, whereas complete drug release was observed within 3–4 h in pH 7.4 phosphate buffer.