聚氨基酸复合微胶囊对Hb的控制释放

以生物相容性好、价格低廉的海藻酸钠(ALG)为聚阴离子芯材,通过静电液滴装置制备了平均粒径在290 μm左右、球形度好、表面光洁的海藻酸钙胶珠;再将生物可降解、具有介入治疗作用的聚精氨酸(PLA)与聚组氨酸(PLH)的混合物作为聚阳离子壁材,在海藻酸钙胶珠表面覆上一层高分子聚合膜以制备聚氨基酸复合微胶囊;并以牛血红蛋白Hb为药物模型,对微胶囊的控制释放性能进行了考察并将其初步应用于体外模拟口服给药。结果表明:聚氨基酸复合微胶囊在前0.5 h的累积释放量均低于40％,溶出结束时累积释放量均达到80%以上;ALG/(PLA-PLH)复合微胶囊和ALG/PLH微胶囊的药物释放速率均低于ALG/PLA微胶囊;于10 min成膜时间内制备的微胶囊具有较高的载药量、包封率和缓释性能;以pH 4.6 HAc-NaAc缓冲液为成膜溶媒制备的微胶囊,Hb持续释放时间和残留量均高于蒸馏水组;前2 h在模拟胃液的pH 1.2 HCl溶媒中累计释放的Hb不超过10％且绝大部分是在模拟肠液环境即pH 6.8 PBS 溶媒中释放的;壳聚糖的引入能在一定程度上延长药物释放时间。聚氨基酸复合微胶囊具备一定的缓释性、pH响应性和生理黏附性,有望成为一种口服给药系统用药物载体。      

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。      

壳聚糖/海藻酸盐微胶囊膜的物质扩散性能研究

针对微囊化细胞三维培养研究背景,以壳聚糖、海藻酸钠为微载体制备材料,采用脉冲电场液滴工艺制备海藻酸钙微球,使之与壳聚糖溶液通过聚电解质络合反应生成选择透过性微囊膜.以传统细胞培养的重要碳源葡萄糖与柠檬酸、氮源L-谷氨酸为小分子模型,以聚乙二醇为测定微囊膜截留相对分子质量的模型分子,开展微胶囊传递性能研究.结果表明,葡萄糖、柠檬酸和L-谷氨酸可以自由透过微囊膜扩散,并且柠檬酸和L-谷氨酸能通过竞争螯合Ca2+引起微囊凝胶结构解聚;采用20 mg/mL海藻酸钠溶液与5万相对分子质量、2 mg/mL壳聚糖溶液制备微胶囊,囊膜的截留相对分子质量为1 500.     

戊二醛交联对盐酸青藤碱微胶囊性能的影响及体外细胞毒性研究

采用W/O/W复乳界面聚合法以戊二醛作为交联剂,制备盐酸青藤碱聚乙烯醇(SM-PVA)微胶囊。扫描电镜和傅里叶红外光谱分析戊二醛用量对SM-PVA微胶囊结构的影响,动态膜透析法研究微胶囊体外药物释放行为,MTT法评价微胶囊体外细胞毒性。结果表明SM-PVA微胶囊表面光滑、分散性良好;随着戊二醛用量增加,微胶囊囊壁增厚,结构紧实;体外药物释放结果显示戊二醛用量及释放介质pH值对药物释放均有影响;且体外细胞毒性结果表明微胶囊对L929细胞无细胞毒性。SM-PVA微胶囊具有缓释性能和良好的生物相容性,可进一步研制成为新型中药给药制剂。     

基于电沉积法制备图案化细胞负载型海藻酸钙水凝胶技术进展

由于海藻酸钙水凝胶具有良好的生物相容性、低毒性、低成本、并且可快速制备等优点,因此可作为生物支架材料。通过构建图案化的具有生物细胞的海藻酸钙水凝胶是生物工程中作为生物支架的重要手段之一。文中在简要介绍电沉积法制备海藻酸钙水凝胶原理的基础之上,着重阐述了近年来基于电沉积法制备图案化海藻酸钙水凝胶所提出的方法,包括电极的图案化、间接电沉积法、电沉积与3D生物打印结合、扫描电极的电沉积法以及双极电化学法,并对制备图案化细胞负载型海藻酸钙水凝胶今后发展中仍需解决的问题进行总结与展望。     

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。     

基于电诱导沉积原理制备形状可控的海藻酸钙-多聚赖氨酸水凝胶微封装胶囊

海藻酸钙水凝胶是一种具有良好生物相容性、生物降解性的生物医用高分子材料。文中提出了一种基于电诱导沉积原理制备形状可控的海藻酸钙-多聚赖氨酸(PLL)水凝胶微封装胶囊。在涂有光刻胶的FTO导电玻璃表面上利用光刻技术制造多种预设图案的微电极,基于电诱导沉积原理在微电极上制备特定几何结构海藻酸钙水凝胶,通过PLL等试剂的处理最终得到环形与六边形结构的海藻酸钙-PLL水凝胶微封装胶囊,酵母细胞包含在微封装胶囊中进行24 h的培养,获得有一定生物活性的细胞。这种方法可以制备用于组织工程学研究的生物支架,将对细胞装配,生物打印以及药物输送等领域有重要的参考价值。     

两种不同优化方法对静电液滴法制备单分散海藻酸钙微球工艺的比较

采用星点设计-效应面法和正交设计两种实验设计方法优化高压静电液滴发生技术制备海藻酸钙微球的工艺,以电压、浓度、距离为自变量,海藻酸钙微球的平均粒径为因变量,对自变量各水平进行多元线性回归和二项式拟合,选取最佳工艺条件制备微球。通过两种方法的对比研究,星点-效应面法在优化静电液滴法制备海藻酸钙微球工艺上的可预测性更强,结果更精确,信息获取量更多,效果更佳。     

储库剂型药物载体微管的制备和生物学评价

报道了以NaCl沥滤/NH_4HCO_3发泡复合法将材料PDLLA/β-TCP制成储库剂型药物载体微管,将抗生素药物装载微管后植入慢性骨髓炎的病灶部位,药物通过微管壁上的孔隙释放,达到局部快速治疗的研究结果。实验中主要对储库剂型药物载体微管的制备和载体微管的生物学评价进行了探讨。结果表明:NaCl沥滤/NH_4HCO_3发泡复合法,比单一NH_4HCO_3发泡法制备的多孔微管具有更好的连通孔结构和力学性能,显示出一定的协同效应,同时可以通过NaCl和NH_4HCO_3的不同比例来调节孔隙率,达到药物释放速率的可设计性。另外,将储库剂型药物载体微管制成材料浸取液,进行细胞毒性试验、急性全身毒性试验、溶血试验、皮肤刺激试验、热源试验、微核试验和肌肉植入等试验,以考察微管复合材料的生物相容性,为临床应用提供可靠的实验室依据。实验结果表明:该材料细胞毒性为0级,无急性全身毒性反应,无溶血反应,无刺激,无致热原,微核试验与阴性对照组比较无显著差异,结果为阴性,植入后对周围组织、肌肉无刺激反应。通过对储库剂型药物载体PDLLA/β-TCP微管的制备研究和生物学评价的实验表明:以NaCl沥滤/NH_4HCO_3发泡复合法可...     

层层自组装法制备肝素微囊及其性能研究

以海藻酸钙微核为模板,采用带正电荷的聚稀丙基铵盐酸盐(PAH)和带负电荷的肝素钠(HEP),通过层层自组装(Layer-by-layer,LbL)技术构建具有多层膜结构和抗凝血活性的药物微囊.采用荧光倒置显微镜、SEM、动态光散射仪、Zeta电位仪和抗凝血仪等进行表征.结果表明,制备的海藻酸钙微核粒径约为1.5μm,尺寸均匀、分散性佳;以ALG为模板制得的LbL微囊具备典型的核壳式结构;Zeta电位检测表明,随包膜层数的增加,微囊的电位呈正负交替的变化趋势;通过体外凝血时间(PT、APtt、TT)检测微囊抗凝血活性,比较了分别以PAH和HEP作为最外层时的生物活性,其中以HEP为最外层的显著增强了材料的抗凝血性能,同时随着组装层数的增加,也提高了微囊的抗凝血性能.     

Preparation of embolic NEMs loading capecitabine

The nanoparticles-embedded microcapsules (NEMs) with smooth surface, good sphericity, excellent dispersivity and uniform particle size distribution were prepared by emulsification combined with electrospraying to extend the sustained release performance of the embolic microcapsules loading capecitabine (CAP). The sodium alginate and chitosan with good biocompatibility were used as the materials and CAP as a small-molecule model drug. The drug loading, encapsulation efficiency and drug release of CAP in the NEMs were investigated. The results showed that the drug-loading and encapsulation efficiency both increased with the increment of chitosan and CAP concentration. The maximum values of drug loading and encapsulation efficiency were 1.97 and 18.01 % respectively when initial CAP concentration was 5.0 g/L and chitosan molecular weight 100 kDa. The cumulative release rate of CAP released from the NEMs was lower than 30 % in 0.5 h, which indicated that there was no obvious initial burst release behavior. In the subsequent 240 h, the release results confirmed that the NEMs had better sustained release properties compared to pure microcapsules, and it might be a new anticancer drug delivery system in the future studies.     

Preparation and characterization of novel sinomenine microcapsules for oral controlled drug delivery

Background: Developing a sustained release drug to cure arthritis is needed. Sinomenine (SIN) is abstracted from sinomenium acutum and widely used in the treatment of various rheumatism and arrhythmia with few side effects. The primary aim of this study is to develop SIN microcapsules with polyelectrolyte multilayers for controlled drug release. Method: SIN microcrystals were encapsulated with chitosan, gelatin, and alginate by layer-by-layer technique, such as (gelatin/alginate)₄ and (chitosan/alginate)₆. The size distribution, zeta-potential, stability, and morphology of the microcapsules were characterized by a particle size analyzer, zetasizer, ultraviolet spectroscopy, and transmission electron microscope, respectively. The in vitro controlled release pattern of SIN was studied using a diffusion cell assembly at physiological pH of 6.8 or 1.4. Results: Light stability of these microcapsules was improved after microencapsulation. Compared with release rate of the SIN microcapsules coated by the poly(dimethyldiallyl ammonium chloride)/alginate and gelatin/alginate multilayers, release rate of the SIN microcapsules coated with chitosan/alginate multilayers was fast. Release rate progressively decreased with the increase of chitosan/alginate bilayer number and the decrease of pH value of release medium. Conclusion: These novel SIN microcapsules may be developed into oral controlled drug delivery for rheumatism and arthritis.     

Preparation and embedding–releasing behavior of polyelectrolyte microcapsule

以高压静电法制备的壳聚糖微球为模板, 与海藻酸钠层层自组装制备多层聚电解质膜, 再以乙酸溶出壳聚糖微球制备出微胶囊. 调节乙酸的浓度及溶出时间以控制核内壳聚糖的残留量, 从而诱导负电性荧光素钠的沉积. 微胶囊内部荧光素钠的浓度随着包埋时间的增加而呈线性地提高, 当荧光素钠溶液的浓度为2 mg/l时其最终包埋的浓度达到10.2 mg/l. 这种聚电解质微囊对于小分子负电荷荧光素钠的释放行为主要受其囊壁和内部模板结构的影响, 盐离子浓度对荧光素钠释放行为的影响较小.     

聚电解质微胶囊的制备及其包埋释放行为

以高压静电法制备的壳聚糖微球为模板,与海藻酸钠层层自组装制备多层聚电解质膜,再以乙酸溶出壳聚糖微球制备出微胶囊.调节乙酸的浓度及溶出时间以控制核内壳聚糖的残留量,从而诱导负电性荧光素钠的沉积.微胶囊内部荧光素钠的浓度随着包埋时间的增加而呈线性地提高,当荧光素钠溶液的浓度为2 mg/l时其最终包埋的浓度达到10.2 mg/l.这种聚电解质微囊对于小分子负电荷荧光素钠的释放行为主要受其囊壁和内部模板结构的影响,盐离子浓度对荧光素钠释放行为的影响较小.     

Development of Biodegradable Drug Delivery System to Treat Addiction

Opiate addiction is a serious problem that has now spread worldwide to all levels of society. Buprenorphine has been used for several years for the treatment of opiate addiction. The objective of this project was to develop sustained-release biodegradable microcapsules for the parenteral delivery of buprenorphine. Biodegradable microcapsules of buprenorphine/poly(lactide-co-glycolide) were prepared using two main procedures based on an in-water drying process in a complex emulsion system. These procedures differ in the way the organic solvent was eliminated: evaporation or extraction. The effect of drug loading and the effect of partial saturation of the aqueous phase with the core material during the in-water solvent evaporation were also studied. The efficiency of encapsulation increased from 11% to 34% when the drug loading was decreased from 20% to 5%. There was no significant change in the efficiency of encapsulation when the aqueous phase was partially saturated with buprenorphine. In changing the solvent removal process from evaporation to extraction, no significant change in the efficiency of encapsulation was observed. The microcapsules prepared by the solvent evaporation were smooth and spherical. However, the microcapsules prepared by the extraction of the organic solvent lost their surface smoothness and became slightly irregular and porous compared with the other batches. The average particle size of the microcapsules was between 14 and 49 μm. The cumulative drug release was between 2% and 4% within the first 24 hr. A sustained drug release continued over 45 days.     

Beta-cyclodextrin-based molecular-recognizable smart microcapsules for controlled release

Novel molecular-recognizable smart microcapsules for controlled release are successfully fabricated in two steps. Firstly, monodispersed poly(N-isopropylacrylamide-co-acrylic acid) microcapsules are prepared via microfluidic emulsion template synthesis; and then, β-cyclodextrin groups are introduced onto the microcapsules by a condensation reaction. The results of Fourier transform infrared spectrometry confirm that β-cyclodextrin moieties are successfully immobilized onto microcapsules by the condensation reaction between carboxylic groups of acrylic acid components on the microcapsules and amino groups of modified β-cyclodextrin monomers. The resultant poly(N-isopropylacrylamide-co-acrylic acid/aminated β-cyclodextrin) (PNA-ECD) microcapsules show a narrow size distribution. The volume phase transition temperature of prepared PNA-ECD microcapsules exhibits a positive shift in the solution containing model guest molecules 2-naphthalenesulfonic acid (NS). Upon recognizing the guest molecules NS, the PNA-ECD microcapsules show an isothermal and reversible molecular-recognizable swelling behavior. Moreover, the release rate of model drug molecules Fluorescein isothiocyanate-labeled dextran loaded in the microcapsules dramatically increases upon recognizing NS molecules. The results provide valuable guidance for the design and fabrication of monodispersed molecular-recognizable microcapsules for controlled release.     

海藻酸钙水凝胶/聚乳酸复合材料的制备与性能

通过化学发泡-冷冻干燥-粒子滤出复合法制备聚乳酸(PLLA)大孔支架, 然后在大孔内以海藻酸钠(SA)、碳酸钙、葡萄糖酸内酯(GDL)为原料, 通过原位相转变制备海藻酸钙水凝胶/聚乳酸复合材料(CA/PLLA); 分别利用SEM、压缩强度测试和细胞培养对CA/PLLA支架的形貌、力学性能及生物相容性进行了研究。结果表明: PLLA具有直径小于2 mm、孔道相互连通的孔洞, 且在大孔中能够形成均匀的CA。CA/PLLA复合材料的压缩强度(2.74 MPa)远大于单一的海藻酸钙水凝胶的压缩强度(0.10 MPa)。在CA/PLLA复合支架中, 软骨细胞呈簇状圆形生长状态, 与其在天然软骨陷窝里生长状态一致。这种软硬结合、天然与合成高分子杂化的CA/PLLA复合材料的力学强度和生物相容性同时得到提高, 可进一步作为骨和软骨修复材料研究。     

Development of biodegradable drug delivery system to treat addiction.

Opiate addiction is a serious problem that has now spread worldwide to all levels of society. Buprenorphine has been used for several years for the treatment of opiate addiction. The objective of this project was to develop sustained-release biodegradable microcapsules for the parenteral delivery of buprenorphine. Biodegradable microcapsules of buprenorphine/poly(lactide-co-glycolide) were prepared using two main procedures based on an in-water drying process in a complex emulsion system. These procedures differ in the way the organic solvent was eliminated: evaporation or extraction. The effect of drug loading and the effect of partial saturation of the aqueous phase with the core material during the in-water solvent evaporation were also studied. The efficiency of encapsulation increased from 11% to 34% when the drug loading was decreased from 20% to 5%. There was no significant change in the efficiency of encapsulation when the aqueous phase was partially saturated with buprenorphine. In changing the solvent removal process from evaporation to extraction, no significant change in the efficiency of encapsulation was observed. The microcapsules prepared by the solvent evaporation were smooth and spherical. However, the microcapsules prepared by the extraction of the organic solvent lost their surface smoothness and became slightly irregular and porous compared with the other batches. The average particle size of the microcapsules was between 14 and 49 microns. The cumulative drug release was between 2% and 4% within the first 24 hr. A sustained drug release continued over 45 days.