中空层状羟基磷灰石微球对溶菌酶的吸附与缓释研究

利用锂钙硼玻璃在磷酸盐溶液中的原位转化反应制备表面多孔且具有中空层状结构的羟基磷灰石(HA)微球,以溶菌酶为蛋白的药物模型,研究了中空层状结构的羟基磷灰石微球对溶菌酶的吸附及缓释特性,结果显示,中空微球对不同浓度的溶菌酶溶液,具有不同的吸附机理,当溶菌酶溶液的浓度低于0.8mg/mL时,溶菌酶的吸附主要发生在微球的外表面,符合Langmuir模型,释放速率较快,48h内基本释放完全;当溶菌酶溶液的浓度高于0.8mg/mL时,溶菌酶扩散进入微球内部及球壁的微孔中,使得吸附量显著增加,满足Henry吸附模型,溶菌酶的释放周期明显增加,可持续释放800h,微球对蛋白具有很好的缓释效果。     

新型中空羟基磷灰石微球/壳聚糖复合药物载体用于药物控制释放（英文）

利用中空羟基磷灰石微球和p H敏感型壳聚糖溶液制备了一种具有良好药物缓释和p H敏感型特性的新型复合药物载体材料。采用组分为19Na2O-17Ca O-64B2O3(wt%)的硼酸盐玻璃在磷酸盐溶液中的原位转化反应制备了多壳层介孔中空HA微球,通过SEM、SEM-EDS、XRD和FTIR等方法对产物微球进行表征。结果表明:微球具有多层介孔中空结构,且属于B型碳酸HA。释药结果表明:中空HA微球在释药初期产生了突释现象,包覆壳聚糖后,复合载体的释药量和释药速率显著下降。与此同时,复合药物载体在不同p H的PBS溶液中表现出p H敏感型药物释放特征,利用浓度20 g/L的壳聚糖溶液包覆的复合载体在p H为6.0、7.4和8.5的PBS溶液中的药物累积释放率分别为85.63%、65.85%和71.85%。     

包埋载药微球的羟基磷灰石/聚氨酯复合组织工程支架的研究

研制具有药物缓释功能的骨组织工程支架, 对载药微球包埋于羟基磷灰石/聚氨酯(HA/PU)支架中的药物缓释体系进行了可行性研究. 首先将盐酸环丙沙星作为模型药物, 包裹于乙基纤维素(EC)微球中, 然后将EC微球与HA/PU材料进行复合, 制备了抗生素药物缓释支架. 结果显示EC微球均匀地分布在HA/PU支架基质中, 未对支架的开孔结构和孔隙形貌构成影响. 与单纯将药物载入HA/PU支架中相比, 复合载药EC微球的HA/PU支架的初期药物暴释明显降低, 药物缓释时间延长. 体外药物释放实验和抑菌实验结果表明, 该载药微球支架具有良好的药物缓释功能和抑菌性能, 是一种集骨修复和治疗于一体的新型组织工程支架材料.     

壳聚糖/羟基磷灰石复合微球的原位合成及体外释药性能

采用原位合成法在乳液体系中制备了壳聚糖/羟基磷灰石(HA)复合微球,并探讨了实验条件对复合微球制备的影响。结果表明,当壳聚糖/HA质量比为4/1时,可以获得球形规则,分散性好,平均粒径为9μm的复合微球。此外,NaOH溶液(1mol/L)的加入量应不少于3mL;交联剂(1mL)的最佳加入浓度为8%;向油相中先加入钙盐比先加入磷酸盐时的成球效果好。以盐酸四环素为模型药物,对复合微球的体外载药和释药性能进行了研究。结果显示,HA的引入大大提高了药物的包封率和载药量,而且使得复合微球比纯壳聚糖微球具有更显著的药物缓释效果。     

同轴电喷射法制备核壳结构聚乳酸载药微球

通过同轴静电喷射法制备核-壳结构聚乳酸载药微球。壳层流体为聚乳酸溶液,核层流体为药物水溶液,其中在核层流体中加入壳聚糖以达到在增加溶液电导率的同时改善聚乳酸的亲水性和功能性的目的。实验研究了核、壳层溶液浓度、流量、喷射电压以及接收距离等因素对微球形貌及结构的影响。研究结果表明,当控制实验条件为壳、核层流速比为3∶1,壳层溶液浓度与核层溶液浓度均为1%(质量浓度),喷射电压为20kV,接收距离为15cm,模型药物浓度2mg/mL时,可以得到粒径1μm左右、具有一定缓释效果的核壳结构载药微球,包封率为76.64%,载药量为7.11%。     

PLLA/HA复合微球的制备

采用了一种新的微球制备方法液滴-冷凝法,以左旋聚乳酸[Poly(L-lactic-acid),PLLA]和羟基磷灰石(Hydroxyaptite,HA)为原料制备了复合微球。采用正交试验,以复合微球的粒径、球形度、成球率和孔隙率为考察指标,研究了PLLA溶液浓度、PLLA/HA质量比及冷凝液的温度梯度对复合微球成型和性能的影响,应用扫描电镜(SEM)对聚乳酸微球的微观形貌、孔隙结构进行了观察和表征。研究结果表明,应用该工艺制备的微球粒径均一,球径可控,其表面和内部都存在丰富的微孔,且孔间互相贯通。当采用较低浓度的PLLA溶液和适中的冷凝液温度梯度时,复合微球的各项指标均较好。该微球材料有望在骨缺损填充等领域得到应用。     

茶多酚/壳聚糖/海藻酸钠纳米微球的制备

目的探讨各因素对制备茶多酚/壳聚糖/海藻酸钠纳米微球载药率、包埋率的影响,研究纳米微球体外释放行为,为后期缓释抗菌膜的制备提供基础。方法采用单因素实验、正交实验考察海藻酸钠溶液浓度、壳聚糖溶液浓度、CaCl_2溶液浓度、茶多酚溶液浓度对纳米微粒载药率、包封率的影响,并考察其体外释放率。结果当海藻酸钠溶液、壳聚糖溶液、CaCl_2溶液、茶多酚溶液的质量浓度分别为15,10,15,0.8 mg/m L时,该工艺条件下制备的纳米微粒载药率为22.71%,包封率为61.38%,且粒径集中在500 nm左右,有较好的缓释效果。结论所得的最佳工艺制备条件为后期做缓释抗菌膜打下良好基础。     

超临界CO2抗溶剂法制备聚乳酸药物缓释微球

以L-聚乳酸为模型体系,超临界CO2为抗溶剂,采用超临界流体抗溶剂法制备聚乳酸微球.考察了压力、温度、溶液浓度、溶液流速、二氯甲烷-丙酮混合溶剂、聚合物分子量等参数对制备微球的形态、粒径及其分布的影响.结果表明,改变工艺参数,可在一定范围内调控微球粒径,所制微球平均粒径0.67～6.64μm,溶液浓度及其流速为主要影响因素;实验条件一定时,采用二氯甲烷-丙酮混合溶剂及强制分散溶液法制备得较小粒径微球.释放度实验结果表明,微球按一级释放方程释药,具缓释效果.     

无机中空微球的应用

中空微球是内部中空的特殊球形材料,与实心球和非球形材料相比,它具有许多特殊和优异的物理化学性质。本文中简单介绍了无机中空微球的特点和制备方法,对无机中空微球在催化剂、药物载体、树脂改性填料方面的应用做了比较全面的综述。中空微球由于其特殊的中空及介孔结构,作为催化剂时,可以提高催化活性,延长催化反应时间;作为药物载体时,可提高药物存储量,并延长缓释时间;中空微球的低密度、高比表面积使其适合作为填料,用于树脂的改性。     

硼酸盐玻璃的原位转化及对浸泡液酸碱度的影响

采用火焰喷球法制备了组成为10Na₂O-10CaO-80B₂O₃(wt%)和19Na₂O-17CaO-64B₂O₃(wt%)的钠钙硼(NCB)玻璃(分别记为S1和S2)微球, 通过pH计、XRD、SEM、SEM-EDS、FTIR和BET研究了两种微球原位转化为中空羟基磷灰石(HA)微球及对浸泡液酸碱度的影响, 并以万古霉素为模型药物, 进一步研究了中空HA微球的缓释性能。结果表明, S1-HA微球具有较大的空腔体积和较好的药物负载性能, 其载药量和载药率分别达到13.5 mg/g和16.8%; 而S2微球对浸泡液pH的影响相对较强, S2-HA微球呈现显著的层状结构, 且具有较好的缓释性能, 其缓释时间可达到60 h。     

BCP ceramic microspheres as drug delivery carriers: synthesis,characterisation and doxycycline release

Resorbable ceramics such as biphasic calcium phosphates (BCP) are ideal candidates as drug delivery systems. The BCP ceramic is based on the optimum balance of the most stable hydroxyapatite (HA) phase and more soluble tricalcium phosphate phase (TCP). Doxycycline is a broad-spectrum antibiotic used for the local treatment of periodontitis. The development of BCP microspheres and its release kinetics with doxycycline have been studied. The BCP ceramic powder were prepared by microwave processing and characterised by X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FT-IR) methods. The BCP microspheres were formed by liquid immiscibility effect using gelatin and paraffin oil. Difference in the morphology of the microspheres as a function of gelatin content has been observed. Scanning electron microscope indicated spherical and porous morphology of the microspheres. Drug incorporation was studied at varying pH and the pH 7 was found to be optimal for drug loading. Release pattern tend to depend on the morphology of BCP microspheres. An optimum release of 80% drug has been observed for BCP microsphere with HA:TCP = 65:35 ratio. The surface area measurement results also correlate with drug release obtained.     

Fabrication and dissolution behavior of hollow hydroxyapatite microspheres intended for controlled drug release

Hollow hydroxyapatite (HA) microspheres were fabricated by a simple spray drying method in this study. Moreover, the dissolution behavior of these hollow HA microspheres after immersion in simulated body fluid (SBF) was also studied. The results indicated that the dissolution of the HA microspheres in SBF is not homogeneous in a layer-by-layer fashion but was preferential at different locations of the particle surface. Generically, dissolution preferentially occurs on the location with looser structure and high porosity of the microspheres. The degradable HA microspheres are expected to have potential applications in bone local drug delivery systems.     

聚烯丙基氯化铵调控下多孔羟基磷灰石微球的合成及作为药物载体的应用研究

选用聚烯丙基氯化铵(PAH)作为晶体生长调节剂, 在水热条件下成功制备了多孔羟基磷灰石(Hydroxyapatite, HAP)中空微球。详细研究了反应时间和添加剂浓度等因素的影响: 150℃水热反应12 h, 控制PAH 浓度0.3~0.5 g/L, 可合成尺寸均匀、孔径密集的HAP中空微球。微球生长经历早期前驱体微结构、异相成核、相转化等不同阶段, 聚合物在各阶段都起到重要的调节作用。以典型的布洛芬(ibuprofen, IBU)作为模型药物, 研究微球的药物负载和脱附能力。结果显示: 多孔微球具有良好的药物负载和释放能力, 吸附量较好, 可达到413.65 mg/g。且药物具有较好的pH响应释放行为, 可作为pH敏感靶向药物载体应用到生物医学等领域。     

荔枝状CaCO3@HA/Fe3O4磁性介孔多级微球的制备

为了克服常规的生物陶瓷微球缺乏靶向功能的缺点, 本研究制备了内核为CaCO₃, 外壳为磁性可调控羟基磷灰石(HA)的新型荔枝状多孔微球。结果表明: 抗肿瘤药物阿霉素(DOX)能有效地负载于磁性HA微球上, 并具备磁性靶向功能。此外, HA外壳具有良好的生物相容性和pH响应特性, 可在模拟酸性肿瘤细胞环境中控制DOX的释放, 有效杀死肿瘤细胞, 并在模拟正常细胞培养环境中减少对正常细胞的毒副作用。这种新型的微球材料具有超顺磁性能, 且微结构可控, 是一种智能化药物控释微球载体, 可以灵敏地释放DOX, 从而有效地实现抗肿瘤活性。     

纳米金刚石/酵母-壳聚糖复合微球的制备及光热控释性能

开发高性能功能性光热凝胶并建立药物控释模型对农药智能输送材料的开发具有重要意义。以酵母-壳聚糖水凝胶(YS-CS)为基体,引入光热材料纳米金刚石(DND),通过碱凝胶法合成了纳米金刚石/酵母-壳聚糖(DND/YS-CS)交联网络结构复合凝胶微球,研究了复合微球的微观结构、力学性能和光热转换性能;以吲哚丁酸(IBA)为模型药物,探讨DND/YS-CS对IBA的负载性能和控释性能,揭示复合微球对IBA的光热控释机制。结果表明：复合微球具有良好的力学性能,在分别超声和离心1 h后,DND含量为2.0 mg/mL复合微球保水能力分别达到70.5%和74%;复合微球具有良好的光热转换能力,一个太阳光强度下,最高温度可达37.6℃;DND含量为1.2 mg/mL复合微球对IBA的吸附量最高,可达到41.73μg/mg;微球在光下药物释放模式符合Korsmeyer-Peppas模型,在光下具有明显的刺激响应行为,药物释放呈现“开-关”模式。通过控制光的照射强度控制药物释放,在农业领域有广阔的应用前景。     

Dissolution behavior of hollow hydroxyapatite microspheres immersed in deionized water

Hollow hydroxyapatite (HA) microspheres were fabricated by plasma spraying method. These microspheres were immersed in deionized water for different periods of time to investigate their dissolution behavior with the starting HA powders as contrast. The results showed that although having a relatively lower crystallinity, the dissolution rate of the HA microspheres is somewhat lower than that of HA powders, which was due to the very dense surface layer of the microspheres. Moreover, open pores were seen on the surface of hollow microspheres after immersion. These results suggest that there might be a novel application in drug delivery for the hollow HA microspheres.     

明胶微球/磷酸镁基骨水泥复合药物缓释体系的构建

采用乳化交联法制备出粒径主要分布在100~300 μm的载药明胶微球, 分析了交联剂含量、药物含量和转速对载药率和包封率的影响及药物含量和转速对微球粒径的影响。对载药明胶微球与磷酸镁基骨水泥进行复合, 探讨微球降解过程中复合体系孔隙率的变化及其在体外药物释放的规律, 以期获得一种具有药物缓释性能的多孔磷酸镁基复合骨水泥。结果表明, 随着葡萄糖浓度增加, 载药率和包封率先上升再下降; 随着药物含量的增加, 载药率保持上升, 包封率先上升后下降; 随着转速增加, 载药率和包封率均下降。综合分析, 在转速为400 r/min、葡萄糖浓度为0.5 g/mL、药物与明胶质量比为1:2的条件下制备的载药明胶微球载药量较高, 且粒径合适。将复合不同比例该载药微球的磷酸镁基骨水泥浸泡在Tris-HCl缓冲溶液中进行体外药物释放研究, 结果表明: 在释放前期(0~10 h)药物释放速率较快, 之后药物释放明显减缓。7 d后, 微球几乎降解完全, 药物释放率达到60%~89%, 达到了一定的药物缓释效果。     

5-Fluorouracil encapsulated HA/PLGA composite microspheres for cancer therapy

5-Fluorouracil (5FU) was successfully entrapped within poly(lactide-co-glycolide) (PLGA) and hydroyapatite (HA) composite microspheres using the emulsification/solvent extraction technique. The effects of HA to PLGA ratio, solvent ratio as well as polymer inherent viscosity (IV) on encapsulation efficiency were investigated. The degradation and drug release rates of the microspheres were studied for 5?weeks in vitro in phosphate buffered solution of pH 7.4 at 37?°C. The drug release profile followed a biphasic pattern with a small initial burst followed by a zero-order release for up to 35?days. The initial burst release decreased with increasing HA content. The potential of HA in limiting the initial burst release makes the incorporation of HA into PLGA microspheres advantageous since it reduces the risk of drug overdose from high initial bursts. The linear sustained drug release profile over the course of 5?weeks makes these 5-FU-loaded HA/PLGA composite microparticles a promising delivery system for the controlled release of chemotherapy drugs in the treatment of cancer.     

Fabrication,characterization and long-term in vitro release of hydrophilic drug using PHBV/HA composite microspheres

In this paper, we fabricated polyhydroxybutyrate-co-hydroxyvalerate (PHBV)/Hydroxyapatite (HA) composite microspheres as a long-term drug delivery system. The characterization and in vitro release properties of the system were investigated. It was observed that the PHBV/HA composite microspheres showed very low initial burst that could be neglected, owing to the high affinity and absorbability of nano-HA particles, and the sustained release lasted more than 10 weeks. The in vitro release rate was controlled by diffusion rate of drugs from polymer matrices, and the release profile can be expressed by the Higuchi equation. From our work, it indicated that PHBV/HA composite microsphere could be a promising long-term drug release system.