海藻酸钠-壳聚糖-桑椹红微囊的制备

以海藻酸钠-壳聚糖为复合囊材采用锐孔法制备桑椹红微囊,探讨了海藻酸钠浓度、壳聚糖浓度、Ca Cl2浓度、桑椹红浓度、针头孔径、下滴高度、温度、转速等因素对微囊包封率的影响。确定了最佳制备工艺条件为海藻酸钠浓度4.0%、壳聚糖浓度2.5%、氯化钙浓度2.0%、桑椹红浓度0.50%、针头孔径0.390mm、下滴高度4cm、温度为20℃、转速为300r·min-1。制得的微囊药物含量为11.28%,包封率为88.93%。     

粒径单分散克拉霉素缓释微球的制备研究

采用膜乳化法结合液中干燥法制备了克拉霉素乙基纤维素微球,当膜孔径为2.8及5.4μm、乙基纤维素浓度为5％～6％及投药量为1:2时,制得的克拉霉素乙基纤维素微球的载药量、包封率及收率均最高.考察了克拉霉素乙基纤维素微球的缓控释性能,结果表明:膜乳化法制得的克拉霉素乙基纤维素微球的缓控释效果明显优于溶剂挥发法,且膜孔径为...     

热磁双重响应性载药微囊的制备及其性能研究

采用LbL模板技术,将天然聚电解质壳聚糖CS和海藻酸钠ALG、磁性纳米颗粒Fe3O4或带负电荷或双亲性磷脂在单分散胶体表面进行组装,制备了一种具有热磁双重响应性的新型载药微囊.通过透射电镜、激光共聚焦显微镜、zeta-电位分析仪、紫外分光光度计等对微囊结构及载药、释药性能进行了表征.实验结果表明:微囊的载药量最高可达到22.40%,且具有磁导向作用.微囊外层组装具有热敏性质的磷脂层能有效地克服壳聚糖/海藻酸钠微囊通透性大而导致在较低温(正常生理环境)的输送过程中药物泄漏问题,而在较高温条件下又可使药物迅速释放,从而实现药物的可控释放.     

磁性微胶囊的制备及其药物缓控释性能

用乳液-凝胶法制备了磁性壳聚糖/海藻酸钠微胶囊. 在壳聚糖/海藻酸钠微胶囊中掺入Fe3O4磁性中空球, 使微胶囊具有磁靶向性能. 以头孢拉定作为模型药物研究了载药磁性微胶囊的载药量、包封率及药物缓控释性能等. 结果表明, 提高头孢拉定的初始浓度可以提高载药量, 却不利于提高药物的包封率. 所制备的微胶囊在各种缓冲溶液中长时间内具有显著的缓释效果, 并具有pH 刺激响应释放的性能, 即在模拟胃液中的药物释放率大大降低, 而在模拟体液和肠液中的释放时间大大延长, 可达50 h以上. 另外, 在外加磁场作用下, 微胶囊表现出良好的磁定向运动性能, 为磁靶向药物输送提供基础.     

含水核载牛血清白蛋白聚氰基丙烯酸丁酯微囊的制备及体外释放

利用界面乳液聚合方法制备了新型含水核载牛血清白蛋白 (BSA)的聚氰基丙烯酸丁酯 (PBCA)纳米微囊 .分别研究了纳米微囊的粒径及其分布 ,表面Zeta电势的变化 .并以牛血清白蛋白为模型药物考察了药物包裹率和载药量的变化以及载药纳米微囊在磷酸缓冲溶液中的体外释放行为 .结果表明 ,所制备的纳米微囊平均粒径为 2 0 0nm ,多分散度为 0 2 2 6;表面Zeta电势的变化证明了BSA是包裹于纳米微囊的内部而不是吸附在其表面 ;包裹率和载药量取决于水相中BSA的初始浓度 ,当BSA的浓度为 0 8mg mL时 ,包裹率和载药量分别为 3 5 %和 0 485× 1 0 - 9mol mg;药物的释放速率取决于纳米微囊的壁厚 ,通过调节壁厚可以达到控释的目的     

BSA载药微囊的制备、表征及体外释放行为

采用复乳法-液中干燥法制备了一系列含有牛血清蛋白(BSA)的聚乙二醇-b-聚(6-(乙酸苄酯)-ε-己内酯-co-ε-己内酯(PEBCL)微囊.分别研究了聚合物结构以及制备条件对微囊粒径、载药量和包封率的影响,同时研究了载药微囊在pH=7.4的磷酸盐缓冲溶液中的体外释放行为.研究表明:微囊的平均粒径13～30 μm,微囊对BSA的载药量和包封率分别最高可以达到14.18%和75.90%,药物的释放行为可控,PEBCL微囊作为蛋白质类药物载体有望在临床上获得应用.     

不同相对分子质量羟乙基纤维素对甲维盐微胶囊制备的影响

采用原位聚合法以三聚氰胺-甲醛树脂为壁材制备了甲维盐微胶囊。 探讨了不同黏均相对分子质量羟乙基纤维素作为乳化剂对微胶囊表面形貌、粒径及其分布、包覆率与载药量的影响,对使用不同黏均相对分子质量羟乙基纤维素作为乳化剂制备的微胶囊的释放性能进行了表征。 结果表明,以相对分子质量较小的羟乙基纤维素制备的微胶囊外形规则、致密且无黏连现象。 随羟乙基纤维素黏均相对分子质量的增加所得微胶囊的平均粒径及粒径分布逐渐增大,包覆率与载药量逐渐减小。 释放性能的研究表明,采用相对分子质量较小的羟乙基纤维素制备的微胶囊的释放性能较好。     

普鲁兰多糖的硬脂酸修饰及其作为纳米药物载体的研究

利用1-(3-二甲氨基丙基)-3-乙基碳二亚胺盐酸盐(EDC)和4-二甲氨基吡啶(DMAP)催化硬脂酸(SA)与具有良好生物相容性的普鲁兰多糖(Pullulan)反应, 将硬脂酸接枝在普鲁兰分子链的羟基上, 得到取代度不同的疏水改性两亲性普鲁兰多糖衍生物PUSA1, PUSA2 及PUSA3, 其临界胶束浓度分别为50, 32, 18 μg/mL; 透射电镜(TEM)图像显示透析法制备的PUSA 自组装颗粒为球形. 以阿霉素为模型药物制备了PUSA 载药纳米粒, 考察了载药纳米粒的载药量、包封率和体外药物释放. 结果表明PUSA3 的包封率高达84%, 载药量达7.79%. 药物可在37 ℃, pH＝7.4 的PBS 溶液中持续释放90 h 以上. 细胞毒性实验(MTT)结果显示当PUSA 的浓度高达1000 μg/mL 时48 h 后细胞存活率依然在90%左右. 流式细胞及荧光分析表明载药纳米粒的细胞摄取率远远高于游离药物. 说明PUSA 是一种新型的有潜在应用价值的药物载体材料.     

肽类药物口服剂型材料及控制释放性能研究Ⅰ.壳聚糖─海藻酸盐微囊对胰岛素的控释作用

应用壳聚糖-海藻酸盐微囊技术制备了一系列胰岛素微囊，并研究了不同反应条件如海藻酸钠浓度、壳聚糖浓度、壳聚糖分子量及壳聚糖溶液pH值对微囊的胰岛素包封率及其释放性能的影响。结果表明，海藻酸钠浓度越高，微囊对胰岛素的包封率越高，在模拟小肠液中释放速率越低；壳聚糖浓度越大，微囊的胰岛素包封率及其在模拟胃液中释放率越高，在模拟肠液中释放达最大值所需时间越长；而随壳聚糖分子量减小，微囊在胃液中释放率增高；壳聚糖溶液pH值的变化对微囊的胰岛素包封率未造成明显影响。     

阿司匹林-蒙脱土-壳聚糖缓释微球的制备及其体外释放性能

利用溶液法预先制备壳聚糖(Cs)-蒙脱土(MMT)复合材料(Cs-MMT),以Cs-MMT、Cs为原料,采用反相悬浮聚合法制得一种新型药物缓释体系阿司匹林-蒙脱土-壳聚糖载药微球(Asp-MMT-Cs)。采用FT-IR、SEM表征了Cs-MMT和Asp-MMT-Cs载药微球的结构及形态;设计正交实验优化了Asp-MMT-Cs载药微球的制备工艺;通过体外释放实验探讨了载药微球在不同模拟释放液中的释药规律。结果表明:所得微球球形度好,粒径分布较均匀;最优工艺制得的载药微球平均粒径为81.20μm,载药量为9.61%,包封率为76.78%。该缓释体系具有pH敏感性,更倾向于在pH较高的磷酸盐缓冲溶液中释放。     

Preparation of insulin-loaded PLA/PLGA microcapsules by a novel membrane emulsification method and its release in vitro

Uniform-sized biodegradable PLA/PLGA microcapsules loading recombinant human insulin (rhI) were successfully prepared by combining a Shirasu Porous Glass (SPG) membrane emulsification technique and a double emulsion-evaporation method. An aqueous phase containing rhI was used as the inner water phase (w1), and PLA/PLGA and Arlacel 83 were dissolved in a mixture solvent of dichloromethane (DCM) and toluene, which was used as the oil phase (o). These two solutions were emulsified by a homogenizer to form a w1/o primary emulsion. The primary emulsion was permeated through the uniform pores of a SPG membrane into an outer water phase by the pressure of nitrogen gas to form the uniform w1/o/w2 droplets. The solid polymer microcapsules were obtained by simply evaporating solvent from droplets. Various factors of the preparation process influencing the drug encapsulation efficiency and the drug cumulative release were investigated systemically. The results indicated that the drug encapsulation efficiency and the cumulative release were affected by the PLA/PLGA ratio, NaCl concentration in outer water phase, the inner water phase volume, rhI-loading amount, pH-value in outer water phase and the size of microcapsules. By optimizing the preparation process, the drug encapsulation efficiency was high up to 91.82%. The unique advantage of preparing drug-loaded microcapsules by membrane emulsification technique is that the size of microcapsules can be controlled accurately, and thus the drug cumulative release profile can be adjusted just by changing the size of microcapsules. Moreover, much higher encapsulation efficiency can be obtained when compared with the conventional mechanical stirring method.     

Control of prolonged drug release and compression properties of ibuprofen microspheres with acrylic polymer, eudragit RS, by changing their intraparticle porosity [corrected]

Prolonged-release spherical micro-matrices of ibuprofen with Eudragit RS were prepared using a novel emulsion-solvent diffusion method. Those particles were termed "microspheres" due to their characteristic sponge-like texture and unique dissolution and compression properties unlike conventional microcapsules or microspheres. The internal porosity of microspheres could be easily controlled by changing the concentration of the drug and the polymer in the emulsion droplet (ethanol). With lower concentration of ibuprofen in the ethanol, the resultant microspheres had a higher porosity, about 50%. The drug release rate from the microspheres was interpreted by the Higuchi model of spherical matrices, which depended only on their internal porosity of the microspheres when size distribution and drug content were the same. The tortuosities in the microspheres were found to be almost constant (3-4) irrespective of porosity, suggesting the same internal texture. Microsphere compressibility was much improved over the physical mixture of the drug and polymer owing to the plastic deformation of their sponge-like structure. The more porous microspheres produced stronger tablets [corrected].     

Preparation and evaluation of albumin microspheres and microcapsules containing cisplatin

Albumin microspheres and microcapsules containing cisplatin (CDDP) were prepared and tested as chemotherapeutic agents for the treatment of hepatocellular carcinoma. CDDP albumin microspheres were prepared by hardening with glutaric aldehyde in accordance with the method to prepare W/O emulsion. On the other hand, microcapsules were prepared by formation of a coacervate by the phase isolation method. CDDP albumin microspheres and microcapsules thus prepared were sieved and sterilized by dry heat at 135 degrees C for 4h prior to use. The content and release of CDDP were determined. The CDDP contents for albumin microspheres and microcapsules were found to be 9.2% and 33.3%, respectively. Release of CDDP in vitro was found to be significantly different between the two formulations. CDDP release in vivo was also investigated by injecting albumin microspheres and microcapsules into the hepatic artery of adult dogs. The blood CDDP concentrations after injection of both formulations were lower than those noted after injection of CDDP injectable solution, indicating that CDDP might be accumulated in the liver at a higher concentration and that use of the two formulations might result in alleviation of CDDP side effects.     

Influence of process parameters on the size distribution of PLA microcapsules prepared by combining membrane emulsification technique and double emulsion-solvent evaporation method

Relatively uniform-sized biodegradable poly(lactide) (PLA) microcapsules with various sizes were successfully prepared by combining a glass membrane emulsification technique and water-in-oil-in-water (w₁/o/w₂) double emulsion-solvent evaporation method. A water phase was used as the internal water phase, a mixture solvent of dichloromethane (DCM) and toluene dissolving PLA and Arlacel 83 was used as the oil phase (o). These two solutions were emulsified by a homogenizer to form a w₁/o primary emulsion. The primary emulsion was permeated through the uniform pores of a glass membrane into the external water phase by the pressure of nitrogen gas to form the uniform w₁/o/w₂ double emulsion droplets. Then, the solid polymer microcapsules were obtained by simply evaporating solvent. The influence of process parameters on the size distribution of PLA microcapsules was investigated, with an emphasis on the effect of oil-soluble emulsifier. A unique phenomenon was found that a large part of emulsifier could adsorb on the interface of internal water phase and oil phase, which suppressed its adsorption on the surface of glass membrane, and led to the successful preparation of uniform-sized double emulsion. Finally, by optimizing the process parameters, PLA microcapsules with various sizes having coefficient of variation (CV) value under 14.0% were obtained. Recombinant human insulin (rhI), as a model protein, was encapsulated into the microcapsules with difference sizes, and its encapsulation efficiency and cumulative release were investigated. The result suggested that the release behavior could be simply adjusted just by changing precisely the diameters of microcapsule, benefited from the membrane emulsification technique.     

Characterization and release behaviors of porous PCL/Eudragit RS microcapsules containing tulobuterol

In this work, porous poly(ɛ-caprolactone) (PCL)/Eudragit RS 100 (ERS-100) microcapsules containing tulobuterol base as a model drug were prepared by a solvent evaporation method and the effect of the quaternary ammonium groups of ERS-100 on the release behaviors of the microcapsules was investigated. The microcapsules prepared with PCL alone showed a stable and smooth surface, whereas porous microcapsules were formed with the addition of ERS-100. Drug loading and encapsulation efficiency of the microcapsules were slightly decreased with an increase of ERS-100 content, resulting from an increase in the porosity of the microcapsules. In an acidic release medium, PCL microcapsules showed slow drug release, whereas PCL/ERS-100 microcapsules showed a faster release rate with an increasing ERS-100 content. These behaviors are likely due to an increase in the diffusion rate of the drugs stemming from an increased hydration of the microcapsules, which results from the interaction between the carboxyl group of the release medium and the quaternary ammonium group of ERS-100.     

Facile fabrication of drug-loaded PEGDA microcapsules for drug evaluation using droplet-based microchip

Droplet-based microfluidic technology can be utilized as a microreactor to prepare novel functional monodisperse microcapsules. In this study, a droplet-based microfluidic chip with surface modification,which allowed the one-step preparation of double emulsion microcapsules. An O/W/O double emulsion using polyethylene(glycol) diacrylate(PEGDA) solution as the intermediate water phase was prepared by regulating the hydrophilicity and hydrophobicity of the chip surface, with PEGDA microcapsules pr...     

Fabrication strategy for amphiphilic microcapsules with narrow size distribution by premix membrane emulsification

Amphiphilic co-polymer, which can maintain the stability of proteins and increase the protein loading efficiency, is considered as an exploring-worthy biodegrade polymer for drug delivery. However, amphiphilic microcapsules prepared by conventional methods, such like mechanical stirring and spray-drying methods, exhibit broad size distributions due to its hydrophilic sequences, leading to poor reproducibility. In this study, we employed poly(monomethoxypoly ethylene glycol-co-D,L-lactide) (mPEG-PLA, PELA), one of common amphiphilic polymers, as model to focus on investigating the process parameters and mechanisms to prepare PELA microcapsules with narrow size distribution and regular sphericity by combining premix membrane emulsification and double emulsion technique. The coarse double emulsion with broad size distribution was repeatedly pressed through Shirasu Porous Glass (SPG) membrane with relatively high pressure to form the fine emulsion with narrow size distribution. Then, the microcapsules with narrow size distribution can be obtained by solvent extraction method. It was found that it was more difficult to obtain PELA microcapsules with narrow size distribution and smooth surface due to its amphiphilic property, compared with the cases of PLA and PLGA. The smooth surface morphology was found to be related to several factors including internal water phase with less volume, slower stirring rate during solidification and using ethyl acetate as oil phase. It was also found that mass ratio of hydrophilic mPEG, stabilizer PVA concentration in external water phase and transmembrane pressure played important role on the distribution of microcapsules size. The suitable preparation conditions were determined as follows: for the membrane with pore size of 2.8 μm, the mass ratio of PLA/mPEG was 19:1, volume ratio of W(1)/O was 1:10 and O/W(2) was 1:5, PVA concentration (w/v) was 1.0%, magnetic stirring rate during solidification was 60 rpm and 300 kPa was chosen as transmembrane pressure. There was a linear relationship between the diameter of microcapsules and the pore size of the membranes. Finally, by manipulating the process parameters, PELA microcapsules with narrow size distributions (coefficient of variation was less than 15%), smooth morphology and various sizes, were obtained. Most importantly, the key factors affecting fabrication have been revealed and mechanisms were illustrated in detail, which would shed light on the research of amphiphilic polymer formulation.     

Preparation and characterization of biodegradable poly(l-lactide)/poly(ethylene glycol) microcapsules containing erythromycin by emulsion solvent evaporation technique

In this work, the producing of a biodegradable poly(l-lactide) (PLA)/poly(ethylene glycol) (PEG) microcapsule by emulsion solvent evaporation method was investigated. The effect of PEG segments added to the PLA microcapsules on the degradation, size distribution, and release behavior was studied. According to the results, PLA/PEG copolymer was more hydrophilic than PLA homopolymer, and with lower glass transition temperature. The surface of PLA/PEG microcapsules was not as smooth as that of PLA microcapsules, the mean diameters of prepared PLA and PLA/PEG microcapsules were 40 and 57 microm, respectively. And spherical forms were observed by the image analyzer and the scanning electron microscope (SEM). Drug release from microcapsules was affected by the properties of PLA/PEG copolymers determined by UV-vis spectra. It was found that the drug release rates of the microcapsules were significantly increased with adding of PEG, which explained by increasing hydrophilic groups.     

Performance of biodegradable microcapsules of poly(butylene succinate), poly(butylene succinate-co-adipate) and poly(butylene terephthalate-co-adipate) as drug encapsulation systems

Poly(butylene succinate) (PBSu), poly(butylene succinate-co-adipate) (PBSA) and poly(butylene terephthalate-co-adipate) (PBTA) microcapsules were prepared by the double emulsion/solvent evaporation method. The effect of polymer and poly(vinyl alcohol) (PVA) concentration on the microcapsule morphologies, drug encapsulation efficiency (EE) and drug loading (DL) of bovine serum albumin (BSA) and all-trans retinoic acid (atRA) were all investigated. As a result, the sizes of PBSu, PBSA and PBTA microcapsules were increased significantly by varying polymer concentrations from 6 to 9%. atRA was encapsulated into the microcapsules with an high level of approximately 95% EE. The highest EE and DL of BSA were observed at 1% polymer concentration in values of 60 and 37%, respectively. 4% PVA was found as the optimum concentration and resulted in 75% EE and 14% DL of BSA. The BSA release from the capsules of PBSA was the longest, with 10% release in the first day and a steady release of 17% until the end of day 28. The release of atRA from PBSu microcapsules showed a zero-order profile for 2 weeks, keeping a steady release rate during 4 weeks with a 9% cumulative release. Similarly, the PBSA microcapsules showed a prolonged and a steady release of atRA during 6 weeks with 12% release. In the case of PBTA microcapsules, after a burst release of 10% in the first day, showed a parabolic release profile of atRA during 42 days, releasing 36% of atRA.     

Preparation and Evaluation of Theophylline Sustained Release Microcapsules Using Coacervation

Preparation of sustained release dosage forms is one of the main objectives in drug formulation. Theophylline that has a narrow therapeutic index, making it a good choice to prepare a sustained release dosage form. Theophylline sustained release microcapsules were prepared by applying the coacervation method. The effect of the type and ratio of polymers, as well as the type of washing solvents, was studied on particle size, drug loading efficiency, and in vitro drug release profile. Results showed that Eudragit RS and RL could be more suitable polymers for preparation of sustained release microcapsules of theophylline when used in ratio of 1:1 and when the washing solvent was hexane.