壳聚糖—海藻酸钠微囊对蛋白质控制释放的研究

采用乳化法制备了可注射用壳聚糖－海藻酸钠微囊，其粒径小于２００μｍ，且具有相对较窄的近似高斯分布。牛血清白蛋白作为模型药物在微囊中的包埋率可超过５０％。通过壳聚糖在海藻酸钠微囊表面的复合，牛血清白蛋白从微囊中的持续释放时间从几个小时延长到半个月以上。     

低分子肝素/壳聚糖/海藻酸钠复合微囊的制备及释药性能

低分子肝素/壳聚糖/海藻酸钠复合微囊的制备及释药性能;壳聚糖; 海藻酸钠; 低分子肝素; 微囊; 释药性能     

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。     

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？…

应用壳聚糖－海藻酸盐微囊技术制备了一系列胰岛素微型,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值对生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度越低;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     

肽类药物口服剂型材料及控制释放性能研究：Ⅱ含有添加剂的？…

应用壳聚糖－海藻酸盐微囊技术制备了一系列含有添加剂的胰岛素微囊,并研究了在添加剂在下,不同反应条件对微囊的胰岛素包封率及其释放性能的影响。结果表明,在添加剂存在下,海藻酸钠浓度越高,微囊在胃液中释放率越大,在模拟小肠液中释放速率越低,并且微球的韧性很强,不易破裂;海藻酸钠与添加剂的质量比越大,微囊的包封率越大,胃液中释放率减小;胰岛素含量直蒿,包封率越小,胃液中释放率越大;明胶和牛血清白蛋白的加入     

肽类药物口服剂型材料及控制释放性能研究──Ⅱ.含有添加剂的壳聚糖-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含有添加剂的胰岛素微囊,并研究了在添力。剂存在下,不同反应条件对微囊的胰岛素包封率及其释放性能的影响．结果表明,在添加剂存在下,海藻酸钠浓度越高,微囊在胃液中释放率越大,在模拟小肠液中释放速率越低,并且微球的韧性很强,不易破裂;海藻酸钠与添加剂的质量比越大,微囊的包封率越大,胃液中释放率减小;胰岛素含量越高,包封率越小,胃液中释放率越大;明胶和牛血清白蛋白的加入使微囊在胃液中释放率显著增大,微球的强度和韧性大大增强,尤其明胶的加入使微囊在模拟小肠液中释放率显著降低,释放达到最大值的时间延长．     

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     

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%。     

壳聚糖微囊的部分特性研究

以壳聚糖为主要材料,制备壳聚糖微囊。微囊直径在０．５－０．８ｍｍ间,微囊在ｐＨ４－１１的缓冲液中稳定,能耐受３０００ｒ／ｍｉｎ离心３０ｍｉｎ以上。用牛血清白和蛋白γ－球蛋白测其通透性,表明随着微囊所在溶液ｐＨ的升高,微囊通透性降低。壳聚糖的分子量在一定范围内对微囊通透性几乎无影响而脱乙酰度对通透笥影响很大。     

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.     

海藻酸钙-壳聚糖微胶囊组成对BSA通透性能影响的研究

对海藻酸钙-壳聚糖微胶囊的牛血清白蛋白(BSA)双向通透性能进行了定量和定性的初步研究, 并初步考察了微胶囊的组成成分及海藻酸钠、壳聚糖的溶液浓度对BSA通透性能的影响. 结果表明海藻酸钙-壳聚糖微胶囊在pH 1.5～2.0时通透性减弱, pH 6.8时通透性增强, 且海藻酸钙微胶囊通透性大于海藻酸钙-壳聚糖微胶囊; 海藻酸钙-壳聚糖微胶囊中壳聚糖浓度越小, 通透性越好; 海藻酸钠浓度的影响不显著.     

微胶囊膜表面化学组成的XPS分析

采用XPS表面表征技术对生物微胶囊膜表面化学组成进行了分析。结果表明,海藻酸钠_壳聚糖_海藻酸钠(ACA)微胶囊表面带负电荷的含C基团与带正电荷的含N基团的相对百分含量分别为30·6%与60·4%,而海藻酸钠_聚赖氨酸_海藻酸钠(APA)微胶囊分别为42·3%与30·0%,因此ACA微胶囊表面比APA微胶囊带更多的正电荷,更有利于蛋白质吸附与细胞粘附。为深入了解生物微胶囊表面引起的机体反应过程、改进微胶囊性能,提供了理论依据。     

壳聚糖-海藻酸盐纳米粒子的制备及其对BSA的载药与释放特性

带相反电荷的聚电解质在水溶液中能通过静电相互作用自组装形成壳聚糖-海藻酸盐纳米粒。利用动态光散射纳米粒度分析仪考察了钙离子及壳聚糖对粒子粒径的影响。结果表明：钙离子的存在可使粒子粒径从268．5nm降为203．4nm,但随着钙离子含量的继续升高,粒径迅速增大,当钙离子浓度大于0．45g／L时形成凝胶。壳聚糖含量的增加和蛋白的包裹均会使粒径增大。所制备的纳米粒对BSA具有较高的包栽能力,并有一定的缓释作用。当壳聚糖投料量增加时,可使BSA在pH=7．4的PBS中的释放减慢。     

Morphologic evolution of Au nanocrystals grown in ionic liquid by plasma reduction

By AFM we report the successful modulation of shell structure (morphology and shell thickness) of microcapsules through tailoring molecular substituents of chitosan. The shell thickness of hollow (HPCS/SA)(n) (n=5, 7, 9) capsules is more than 3 times that of the (QACS/SA)(n) (n=5, 7, 9) capsules, due to less charges carried by the neutral -NH(2) substituent group and the induced coily conformation in HPCS, while more charges carried by the positively charged -N(CH(3))(3)(+) substituent and the induced extended conformation in QACS (HPCS: hydroxyl propyl chitosan; QACS: quaternary ammonium chitosan; SA: sodium alginate). The ultrathin shells of microcapsules assembled in this work by the layer-by-layer (LbL) self-assembly technique rather than the traditional method of mixing CS, SA and CaCl(2) enable the thickness modulation characterization by AFM on the atomic scale. These microcapsules with tunable shell thickness provide important guidance for potential drug delivery and sustained release.     

Chitosan-g-MPEG-modified alginate/chitosan hydrogel microcapsules: a quantitative study of the effect of polymer architecture on the resistance to protein adsorption

The chemical modification of the alginate/chitosan/alginate (ACA) hydrogel microcapsule with methoxy poly(ethylene glycol) (MPEG) was investigated to reduce nonspecific protein adsorption and improve biocompatibility in vivo. The graft copolymer chitosan-g-MPEG (CS-g-MPEG) was synthesized, and then alginate/chitosan/alginate/CS-g-MPEG (ACAC(PEG)) multilayer hydrogel microcapsules were fabricated by the layer-by-layer (LBL) polyelectrolyte self-assembly method. A quantitative study of the modification was carried out by the gel permeation chromatography (GPC) technique, and protein adsorption on the modified microcapsules was also investigated. The results showed that the apparent graft density of the MPEG side chain on the microcapsules decreased with increases in the degree of substitution (DS) and the MPEG chain length. During the binding process, the apparent graft density of CS-g-MPEG showed rapid growth-plateau-rapid growth behavior. CS-g-MPEG was not only bound to the surface but also penetrated a certain depth into the microcapsule membranes. The copolymers that penetrated the microcapsules made a smaller contribution to protein repulsion than did the copolymers on the surfaces of the microcapsules. The protein repulsion ability decreased with the increase in DS from 7 to 29% with the same chain length of MPEG 2K. CS-g-MPEG with MPEG 2K was more effective at protein repulsion than CS-g-MPEG with MPEG 550, having a similar DS below 20%. In this study, the microcapsules modified with CS-g-MPEG2K-DS7% had the lowest IgG adsorption of 3.0 ± 0.6 μg/cm(2), a reduction of 61% compared to that on the chitosan surface.     

Rose bengal-grafted biodegradable microcapsules: singlet-oxygen generation and cancer-cell incapacitation

Rose bengal-grafted chitosan (RB-CHI), synthesized through dehydration between amino and carboxyl functional groups under mild conditions, was coated onto the outer layer of preformed biodegradable microcapsules consisting of sodium alginate and chitosan. The fabricated photosensitive microcapsules were characterized by optical microscopy, scanning electron microscopy, and confocal laser scanning microscopy. The assembled materials maintained intact spherical morphology and thus showed good ability to form thin films. Electron spin resonance spectroscopy allowed direct observation of the generation of singlet oxygen ((1)O(2)) from photosensitive microcapsules under light excitation at about 545 nm. Furthermore, with increasing light radiation, the content of (1)O(2) increased, as detected by a chemical probe. In vitro cellular toxicity assays showed that RB-CHI-coated photosensitive microcapsules exhibit good biocompatibility in darkness and high cytotoxicity after irradiation, and could provide new photoresponsive drug-delivery vehicles.     

丁烯氟虫腈缓释微胶囊的制备及其性能

以丁烯氟虫腈为囊芯化合物,带有相反电性的壳聚糖和海藻酸钠为囊壁材料,采用层层自组装技术制备了丁烯氟虫腈微胶囊,通过流点法筛选出十二烷基苯磺酸钠为丁烯氟虫腈的分散稳定剂。 对制备的微胶囊进行了表征,系统研究了丁烯氟虫腈微胶囊的载药量、包封率、缓释性能和抗光解性能随着组装层数增加的变化规律。 结果表明,组装层数为6~8层的丁烯氟虫腈微胶囊的包封率达到80%以上,达最高释放量所需要的时间为60 h,光解率降到20%以下,综合效果最好。     

Preparation and Characterization of a Novel Drug Delivery System: Biodegradable Nanoparticles in Thermosensitive Chitosan/Gelatin Blend Hydrogels

A novel injectable in situ gelling drug delivery system (DDS) consisting of biodegradable N-(2-hydroxyl) propyl-3-trimethyl ammonium chitosan chloride (HTCC) nanoparticles and thermosensitive chitosan/gelatin blend hydrogels was developed for prolonged and sustained controlled drug release. Four different HTCC nanoparticles, prepared based on ionic process of HTCC and oppositely charged molecules such as sodium tripolyphosphate, sodium alginate and carboxymethyl chitosan, were incorporated physically into thermosensitive chitosan/gelatin blend solutions to form the novel DDSs. Resulting DDSs interior morphology was evaluated by scanning electron microscopy. The effect of nanoparticles composition on both the gel process and the gel strength was investigated from which possible hydrogel formation mechanisms were inferred. Finally, bovine serum albumin (BSA), used as a model protein drug, was loaded into four different HTCC nanoparticles to examine and compare the effects of controlled release of these novel DDSs. The results showed that BSA could be sustained and released from these novel DDSs and the release rate was affected by the properties of nanoparticle: the slower BSA release rate was observed from DDS containing nanoparticles with a positive charge than with a negative charge. The described injectable drug delivery systems might have great potential application for local and sustained delivery of protein drugs.     

Disintegration-controllable stimuli-responsive polyelectrolyte multilayer microcapsules via covalent layer-by-layer assembly

The disintegration-controllable stimuli-responsive polyelectrolyte multilayer microcapsules have been fabricated via the covalent layer-by-layer assembly between the amino groups of chitosan (CS) and the aldehyde groups of the oxidized sodium alginate (OSA) onto the sacrificial templates (polystyrene sulfonate, PSS) which was removed by dialysis subsequently. The covalent crosslinking bonds of the multilayer microcapsules were confirmed by FTIR analysis. The TEM analysis showed that the diameter of the multilayer microcapsules was <200nm. The diameter of the multilayer microcapsules decreased with the increasing of the pH values or the ionic strength. The pH and ionic strength dual-responsive multilayer microcapsules were stable in acidic and neutral media while they could disintegrate only at strong basic media.