盐酸多西环素羧甲基壳聚糖微球的体外释放研究

目的:探讨各因素对盐酸多西环素羧甲基壳聚糖微球体外释放度的影响。方法:采用乳化-交联固化法制备盐酸多西环素羧甲基壳聚糖微球(doxycycline hydrochloride-carboxymethyl chitosan-microspheres,DXY-CMCTS-MS),采用动态透析法测定体外释药性能,用紫外分光法测定盐酸多西环素浓度,绘制其释放曲线。结果:释放介质pH越大,交联剂量越大,固化时间越长,药物/载体比例越小,药物的释放则越慢。结论:该制剂制备工艺切实可行,所得DXY-CMCTS-MS具有明显的缓释效果。     

壳聚糖及其衍生物体外抗幽门螺杆菌作用及影响因素

目的研究壳聚糖及其衍生物在体外对幽门螺杆菌(Hp)的抑菌作用及其影响因素。方法采用打孔法检测了不同浓度、pH值、脱乙酰度壳聚糖及羧甲基壳聚糖在体外对Hp的抑菌作用。结果①壳聚糖和羧甲基壳聚糖在体外对3株Hp标准菌株具有普遍的抑菌作用;②在pH 6~4范围内,随pH值降低,抗菌作用增强,差异有显著性(P<0.01),最佳pH值为4;③70%、88.5%脱乙酰度壳聚糖及羧甲基壳聚糖的抗Hp作用差异有显著性(P<0.01~0.05),抑菌强度依次为DD70壳聚糖、DD88.5壳聚糖和羧甲基壳聚糖;④在质量浓度为10 g.L-1~50 g.L-1范围内羧甲基壳聚糖抗Hp作用差异无显著性;在质量浓度为5 g.L-1~20 g.L-1范围内70%、88.5%脱乙酰度壳聚糖抗Hp作用差异也无显著性(P>0.05)。结论①壳聚糖和其衍生物对Hp有普遍的抑菌作用;②壳聚糖及其衍生物的抗Hp作用受多种因素影响,其中pH值对壳聚糖抗菌作用的影响最为明显,在pH值6~4范围内,壳聚糖的抗菌活性随着pH值的下降而增强;③壳聚糖的脱乙酰度、结构(化学修饰)及分子量也影响壳聚糖的抗菌活性,不同的细菌所要求的脱乙酰度、修饰基团和分子量有着明显的差异。     

海藻酸钙凝胶微球中模型药物的pH值依赖性释放

目的:考察海藻酸钙凝胶微球中模型药物的pH值依赖性释放.方法:以硝苯地平为模型药,采用滴制法制备了含药微球;考察了含药微球在不同pH值介质中的释放特性.结果:含药微球在水及pH 1.0的介质中几乎不溶胀,12 h累积释放百分率为23.1%和23.4%;在pH6.8的介质中微球溶胀至完全溶蚀,且呈现缓慢释放的趋势,12 h药物的累积释放百分率为92.5%;换介质的释放中,0～2 h微球几乎不溶胀,2 h累积释放8.4%,介质pH改变后微球很快崩解,3 h累积释放82.4%.结论:海藻酸钙凝胶微球中硝苯地平的释放具有pH值依赖性,在pH 6.8的介质中缓释.     

芹菜素壳聚糖微球的制备及体外释药研究

目的以芹菜素为模型药物、脱乙酰壳聚糖为药物载体,制备芹菜素壳聚糖微球,并测定微球中芹菜素的体外释放度。方法采用复乳-乳化化学交联法制备微球,正交试验优化微球制备的工艺,高效液相色谱法检测芹菜素含量。结果最佳工艺制备4批微球,形态良好,微球圆整,平均载药量为8.54%,平均包封率为69.69%,平均粒径为84.33μm。微球在pH 6.8和pH 7.4的磷酸盐缓冲液中释放36 h。结论所选制备工艺稳定,适用于芹菜素壳聚糖微球的制备,体外药物释放结果显示,微球具有良好的缓释效果。     

戊二醛一步固化法制备氟尿嘧啶壳聚糖微球

以壳聚糖为载体,戊二醛为交联剂,氟尿嘧啶为模型药物,采用一步固化法制备氟尿嘧啶壳聚糖微球制剂.以外观和包封率为指标优化了处方,并考察了交联剂浓度和交联时间对微球体外释放行为及溶胀度的影响.采用扫描电镜和红外光谱对微球结构进行表征.所得载药微球的载药量和包封率为33.5%、51.2%,平均粒径为(6.8±1.8)μm,30 min 时突释量为33.5%.     

氟脲嘧啶白蛋白微球的体外释放

本文报告了氟脲嘧啶白蛋白微球的体外释放特性。结果表明微球固化温度影响其释放速率。１００℃制备的微球释放最快，１８０℃制备微球释放最慢，二者相差几乎一倍。１５０℃制备的微球其释放速度介于二者之间。     

阿莫西林脉冲释药微丸的研制

目的:制备阿莫西林脉冲释药微丸。方法:取空白丸芯分别以含药层、溶胀层(羧甲基淀粉钠)和控释层(乙基纤维素水分散体)顺序依次进行包衣制备阿莫西林脉冲释药微丸。采用紫外法和篮法考察溶胀层(12%、16%、20%)和控释层包衣增重(24%、28%、32%)及不同介质(水、盐酸、pH6.8磷酸盐缓冲液)对药物释放的影响。结果:溶胀层和控释层包衣增重对脉冲控释微丸的释药时滞和释放速率具有显著影响,药物释放情况不受介质pH值的影响;溶胀层和控释层包衣增重分别为16%、28%时制备的微丸时滞时间约为4h,时滞后4h累积释药率达到80%。结论:所制备的阿莫西林脉冲释药微丸具有体外脉冲释放作用。     

交联固化时间对利多卡因水凝胶贴剂的影响

目的 研究交联固化时间对利多卡因水凝胶贴剂的初黏力、持黏力、剥离强度、体外释放度等的影响.方法 以初黏力、持黏力、剥离强度为黏性评价指标,采用桨碟法测定体外释放度,用计算相似因子f2值比较释放度,以水凝胶溶胀率和弹性模量E'分析其内部结构和成型机理.结果 初黏力、持黏力、剥离强度在交联固化前7d迅速降低,之后趋于稳定;利多卡因的体外释放度、水凝胶溶胀率和弹性模量E'随着交联固化时间的增加先增加再趋于稳定.结论 交联固化的初始7d为快速反应期,对初黏力、持黏力、剥离强度体外释放度的影响较大.交联固化7d之后,凝胶交联网络基本形成,水凝胶贴剂的质量相对稳定.     

依托泊苷鼻用壳聚糖微球的制备及体外释放度考察

目的研制依托泊苷鼻黏膜给药壳聚糖微球,对微球的制备方法及体外释放度进行考察.方法以壳聚糖为栽体,甲醛为交联剂,采用乳化交联固化法制备微球,对微球的粒径、形态及体外释药进行研究.结果微球的外观圆整,平均粒径为(46.9±0.7)μm,78.4 %的微球粒径在30～70μm范围内,体外释药符合Higuchi模型.结论依托泊苷壳聚糖微球制备工艺简单、稳定,包封率高,药物释放符合鼻腔给药要求.     

阿奇霉素缓释微丸体外释药影响因素考察

考察影响阿奇霉素缓释微丸体外释药的各种因素,为阿奇霉素缓释制剂的研制提供实验依据。方法选用微晶纤维素为空白丸芯,将阿奇霉素制成缓释微丸,通过测定体外释放度,考察EC粘度及增重、致孔剂用量、释放介质pH值对阿奇霉素缓释微丸体外释药速率的影响。结果 EC粘度、包衣增重、致孔剂用量、释放介质pH值对释药速率有显著影响。结论选用适宜包衣材料及致孔剂,调节包衣增重,可制备具有理想释药行为的阿奇霉素缓释微丸。     

Synthesis and characterization of cross-linked chitosan microspheres for drug delivery applications

The present study deals with the synthesis and characterization of cross-linked chitosan microspheres containing an hydrophilic drug, hydroquinone. The microspheres were prepared by the suspension cross-linking method using glutaraldehyde as the cross-linking agent of the polymer matrix. Perfectly spherical cross-linked hydrogel microspheres loaded with hydroquinone were obtained in the size range of 20–100 μm. The effect of the degree of polymer cross-linking, chitosan molecular weight, chitosan concentration and amount of the encapsulated drug on the hydroquinone release kinetics was extensively investigated. It was found that slower drug release rates were obtained from microspheres prepared by using a higher initial concentration of chitosan, a higher molecular weight of chitosan or/and a lower drug concentration. Most importantly, it was shown that the release rate of hydroquinone was mainly controlled by the polymer cross-linking density and, thus, by the degree of swelling of the hydrogel matrix.     

Synthesis and characterization of cross-linked chitosan microspheres for drug delivery applications

The present study deals with the synthesis and characterization of cross-linked chitosan microspheres containing an hydrophilic drug, hydroquinone. The microspheres were prepared by the suspension cross-linking method using glutaraldehyde as the cross-linking agent of the polymer matrix. Perfectly spherical cross-linked hydrogel microspheres loaded with hydroquinone were obtained in the size range of 20-100 microm. The effect of the degree of polymer cross-linking, chitosan molecular weight, chitosan concentration and amount of the encapsulated drug on the hydroquinone release kinetics was extensively investigated. It was found that slower drug release rates were obtained from microspheres prepared by using a higher initial concentration of chitosan, a higher molecular weight of chitosan or/and a lower drug concentration. Most importantly, it was shown that the release rate of hydroquinone was mainly controlled by the polymer cross-linking density and, thus, by the degree of swelling of the hydrogel matrix.     

Preparation and characterization of Mitomycin-C loaded chitosan-coated alginate microspheres for chemoembolization

Mitomycin-C loaded and chitosan-coated alginate microspheres were prepared for use in chemoembolization studies. In this respect, first alginate microspheres were prepared by using a spraying method using an extrusion device with a small orifice and following suspension cross-linking in an oil phase. Chitosan-coating onto the alginate microspheres was achieved by polyionic complex formation between alginate and chitosan. CaCl₂ was used as a cross-linker for alginate microspheres. The obtained chitosan-coated alginate microspheres were spherical shaped and ～100–400?µm average size. The microspheres were evaluated based on their swellability and the swelling ratio was changed between 50–280%. CaCl₂ concentration, stirring rate, chitosan molecular weight, chitosan concentration and time for coating with chitosan were selected as the effective parameters on microsphere size and swelling ratio. Equilibrium swellings were achieved in ～30?min. On the other hand, chitosan molecular weight, chitosan concentration and time for coating with chitosan were found as the most effective parameters on both drug loading ratio and release studies. Maximum drug loading ratio of 65% was achieved with high molecular weight (HMW) chitosan, highest chitosan concentration (i.e. 1.0% v/v) and shortest time for coating with chitosan (i.e. 1?h) values.     

Preparation and characterization of Mitomycin-C loaded chitosan-coated alginate microspheres for chemoembolization

Mitomycin-C loaded and chitosan-coated alginate microspheres were prepared for use in chemoembolization studies. In this respect, first alginate microspheres were prepared by using a spraying method using an extrusion device with a small orifice and following suspension cross-linking in an oil phase. Chitosan-coating onto the alginate microspheres was achieved by polyionic complex formation between alginate and chitosan. CaCl(2) was used as a cross-linker for alginate microspheres. The obtained chitosan-coated alginate microspheres were spherical shaped and approximately 100-400 microm average size. The microspheres were evaluated based on their swellability and the swelling ratio was changed between 50-280%. CaCl(2) concentration, stirring rate, chitosan molecular weight, chitosan concentration and time for coating with chitosan were selected as the effective parameters on microsphere size and swelling ratio. Equilibrium swellings were achieved in approximately 30 min. On the other hand, chitosan molecular weight, chitosan concentration and time for coating with chitosan were found as the most effective parameters on both drug loading ratio and release studies. Maximum drug loading ratio of 65% was achieved with high molecular weight (HMW) chitosan, highest chitosan concentration (i.e. 1.0% v/v) and shortest time for coating with chitosan (i.e. 1 h) values.     

Cross-linked starch microspheres: Effect of cross-linking condition on the microsphere characteristics

Cross-linked starch microspheres were prepared using different kinds of cross-linking agents. The influence of several parameters on morphology, size, swelling ratio and drug release rate from these microspheres were evaluated. These parameters included cross-linker type, concentration and the duration of cross-linking reaction. Microspheres cross-linked with glutaraldehyde had smooth surface compared with those prepared with epichlorhydrine or formaldehyde. The particle size increased with increasing the cross-linking time and increasing the drug loading. Swelling ratio of the particles was a function of cross-linker type but not the concentration or time of cross-linking. Drug release from starch microspheres was measured in phosphate buffer and also in phosphate buffer containing alpha-amylase. Results showed that microspheres cross-linked with epichlorhydrine released all their drug content in the first 30 minutes. However, cross-linking of the starch microspheres with glutaraldehyde or formaldehyde decreased drug release rate. SEM and drug release studies showed that cross-linked starch microspheres were susceptible to the enzymatic degradation under the influence of alpha-amylase. Changing the enzyme concentration from 5000 to 10,000 IU/L, increased drug release rate but higher concentration of enzyme (20,000 IU/L) caused no more acceleration.     

5-fluorouracil loaded chitosan microspheres for chemoembolization

In this study, chitosan microspheres were prepared by a suspension cross-linking technique. A petroleum ether/mineral oil mixture was used as the suspension medium which includes an emulsifier, e.g. Tween-80. Glutaraldehyde was used as the cross-linker. 5-Fluorouracil was incorporated in the matrix for the possible use of the microspheres in chemoembolization. The size and size distribution of the chitosan microspheres varied in the size range of 100-200 microns, by changing the emulsifier concentration, stirring rate, chitosan/solvent ratio and drug/chitosan solution ratio. In summary, the size and size distribution of the microspheres decreased when the emulsifier concentration and stirring rate were increased. Smaller microspheres with narrower size distributions were obtained when the chitosan/solvent ratio and drug/chitosan ratio were lower. It was possible to load the chitosan microspheres with 5-FU to a concentration of 10.4 mg 5-FU/g chitosan. Around 60% of the loaded drug was released within the first 24 h, then the release rate became much slower.     

Ionically cross-linked chitosan microspheres for controlled release of bioactive nerve growth factor

Controlled release of neurotrophic factors to target tissue via microsphere-based delivery systems is critical for the treatment strategies of diverse neurodegenerative disorders. The present study aims to investigate the feasibility of the controlled release of bioactive nerve growth factor (NGF) with ionically cross-linked chitosan microspheres (NGF-CMSs). The microspheres were prepared by the emulsion-ionic cross-linking method with sodium tripolyphosphate (STPP) as an ionic cross-linking agent. The size and distribution of the microspheres, SEM images, Fourier transform infra red spectroscopy (FT-IR), encapsulation efficiency, in vitro release tests and bioactivity assay were subsequently evaluated. We found that the microspheres had relatively rough surfaces with mean sizes between 20 and 31μm. FT-IR results provided evidence of ionic interaction between amino groups and phosphoric groups of chitosan and STPP. The NGF encapsulation efficiency ranged from 63% to 88% depending on the concentration of STPP. The in vitro release profiles of NGF from NGF-CMSs were influenced by the concentration of STPP. NGF-CMSs which were cross-linked with higher concentration of STPP showed slower but sustained release of NGF. In addition, the released NGF from NGF-CMSs was capable of maintaining the viability of PC12 cells, as well as promoting their differentiation. Taken together, our findings suggest that NGF-CMSs are capable of releasing bioactive NGF over 7 days, thus having potential application in nerve injury repair.     

Design and characterisation of doxorubicin-releasing chitosan microspheres for anti-cancer chemoembolisation

The aims of this study were to design and characterise doxorubicin-loaded chitosan microspheres for anti-cancer chemoembolisation. Doxorubicin-loaded chitosan microspheres were prepared by emulsification and cross-linking methods. Doxorubicin–chitosan solution was initially complexed with tripolyphosphate (TPP) to improve drug loading capabilities. Doxorubicin-loaded chitosan microspheres were highly spherical and had approximately diameters of 130–160?µm in size. Drug loading amount and loading efficiency were in the range 3.7–4.0% and 68.5–85.8%, respectively, and affected by TPP concentration, drug levels and cross-linking time. Doxorubicin release was affected by TPP complexation, cross-linking time and release medium. Especially, lysozyme in release media considerably increased drug release. Synergistic anti-cancer activities of doxorubicin-releasing chitosan microspheres were confirmed to VX2 cells in the rabbit auricle model compared with blank microspheres. Doxorubicin-loaded chitosan microspheres can efficiently be prepared by TPP gelation and cross-linking method and developed as multifunctional anti-cancer embolic material.     

A novel method to prepare magnetite chitosan microspheres conjugated with methotrexate (MTX) for the controlled release of MTX as a magnetic targeting drug delivery system

The purpose of the present study is to develop a new method to prepare magnetite chitosan microspheres conjugated with methotrexate (MTX) for the controlled release of MTX as a magnetic targeting drug delivery system. MTX was first conjugated to the chitosan chain via a peptide bond and then a suspension cross-linking technique was used for the production of magnetic chitosan microspheres with glutaraldehyde as the cross-linker. The MTX-loading capacity of the magnetic chitosan microspheres was determined and drug release experiments were also carried out to discuss the MTX release behavior. All the data support that the magnetic chitosan-MTX microspheres prepared in this method would have great potential application in magnetic targeting drug delivery technology.     

Chitosan and chondroitin microspheres for oral-administration controlled release of metoclopramide.

This study investigated the usefulness of chitosan and chondroitin sulphate microspheres for controlled release of metoclopramide hydrochloride in oral administration. Microspheres were prepared by spray drying of aqueous polymer dispersions containing the drug and different amounts of formaldehyde as cross-linker. Drug release kinetics were investigated in vitro in media of different pH. Chondroitin sulphate microspheres scarcely retarded drug release, regardless of cross-linker concentration and medium pH, and were thus not further characterized. Chitosan microspheres prepared with more than 15% formaldehyde (w/w with respect to polymer) showed good control release (more than 8 h), and release rates were little affected by medium pH. Release from chitosan microspheres prepared with 20% formaldehyde was independent of pH, suggesting that this may be the most appropriate formulation. The size distribution of the chitosan microparticles was clearly bimodal, with the smaller-diameter subpopulation corresponding to microsphere fragments and other particles. Electron microscopy showed the chitosan microspheres to be almost-spherical, though with shallow invaginations. The kinetics of drug release from chitosan microspheres were best fitted by models originally developed for systems in which release rate is largely governed by rate of diffusion through the matrix.