人同种异体骨载异烟肼-壳聚糖缓释微球的制备和体内外释药特性

背景：壳聚糖微球具有良好的生物相容性及抗菌活性,被广泛地运用于各种药物缓释系统中。目的：制备人同种异体骨载异烟肼-壳聚糖微球,并分析其体内释药性能。方法：用喷雾干燥法制备异烟肼-壳聚糖微球,进行体外45d的药物释放实验。将单独装载异烟肼的异体骨块（对照组）和装载异烟肼-壳聚糖微球的异体骨块（实验组）分别植入家兔两侧髂骨,采用高效液相色谱法检测药物体内释放情况。结果与结论：异烟肼-壳聚糖微球外观呈圆形、表面光滑、分散良好;平均粒径（3.33±0.9）μm,载药率（16.25±1.24）%。体外药物释放实验显示无突释现象,24h释放20%左右,45d释放76%,释放曲线较平缓,释放稳定;数学模型拟合符合Ritger-Peppas模型。实验组异烟肼浓度在前28d内缓慢升高,其后缓慢下降,持续56d以上,浓度38.50～155.75μg/g;对照组异烟肼浓度在1周左右达高峰,为1982.5μg/g,21d后骨块周围药物不能测到。说明异烟肼-壳聚糖缓释微球在体内外均可以缓慢平稳释放异烟肼,且持续时间长。提示人同种异体骨载异烟肼-壳聚糖缓释微球复合体可以作为骨结核病灶清除后的一种置入材料,在提供机械支持的同时进行长时间的局部化疗。     

长效缓释双药物人工骨的制备及释放特性

背景:利用可降解缓释生物材料包载利福平或异烟肼制成50μm 以下的缓释降解肺靶向微球已多有报道,主要用于静脉注射肺靶向治疗研究.目的:研制长效缓释双组分药物人工骨,筛选最佳制备工艺并行体外释药特性观察.方法:采用乳剂-溶剂挥发法正交设计优化制备工艺,分别制备利福平聚乳酸-羟基乙醇共聚物微球和异烟肼聚乳酸-羟基乙醇共聚物微球.利用生物黏合剂将两种微球加工成长效缓释双组分药物人工骨.结果与结论:按照优化工艺分别制得聚乳酸-羟基乙醇共聚物载利福平26%、异烟肼28%的微球,并按质量各50%制成人工骨,体外释放90 d保持0.02,0.03 mg/L药物浓度.表明该人工骨有望为骨结核治疗用提供一种新型的方法.     

缓释双药物载体制备与性能

背景：骨结核患者常规用药,病灶处结核药物的有效浓度低,治疗效果差。目的：制备一种可直接植入骨结核病灶内的,且具有在骨结核周围组织能够长期保持一定的抗结核药物浓度,起到提高骨结核的治愈率有效治疗的新型生物材料。方法：采用乳剂-溶剂挥发法制备利福平-聚乳酸-羟基乙酸共聚物微球和异烟肼-聚乳酸-羟基乙酸共聚物微球,利用生物黏合剂α-氰基丙烯酸烷基酯将2种微球加工成长效缓释双组分药物载体,观察缓释双药物载体体外释药特性;然后将缓释双药物载体置入兔股骨转子间骨缺损部位,观察载药缓释载体植入后不同时间点药物释放浓度、组织相容性及骨缺损的愈合情况。结果与结论：利福平-聚乳酸-羟基乙酸微球平均粒径（240±13）μm,载药率为（26±1.5）%。异烟肼-聚乳酸-羟基乙酸微球平均粒径（250±10）μm,载药率为（28±1.8）%。利福平、异烟肼,90 d体外累积释放率可达到80%和90%。90 d体内释放利福平和异烟肼的浓度可达（0.5±0.4）和（0.6±0.3）μg/g。缓释双药物载体置入兔股骨转子间骨缺损部位可见筋膜、肌纤维之间出现少量中性粒细胞浸润,59 d 后肌肉组织中性粒细胞明显减少,X射线平片显示骨缺损明显缩小。提示该载体能够长时间保持骨结核周围组织中一定的药物浓度,弥补血中药物浓度不足,有望在骨结核手术治疗中提供一种新型的双药物缓释载体。     

缓释双药物载体制备与性能*

背景：骨结核患者常规用药,病灶处结核药物的有效浓度低,治疗效果差。目的：制备一种可直接植入骨结核病灶内的,且具有在骨结核周围组织能够长期保持一定的抗结核药物浓度,起到提高骨结核的治愈率有效治疗的新型生物材料。方法：采用乳剂-溶剂挥发法制备利福平-聚乳酸-羟基乙酸共聚物微球和异烟肼-聚乳酸-羟基乙酸共聚物微球,利用生物黏合剂α-氰基丙烯酸烷基酯将2种微球加工成长效缓释双组分药物载体,观察缓释双药物载体体外释药特性;然后将缓释双药物载体置入兔股骨转子间骨缺损部位,观察载药缓释载体植入后不同时间点药物释放浓度、组织相容性及骨缺损的愈合情况。结果与结论：利福平-聚乳酸-羟基乙酸微球平均粒径(240±13)μm,载药率为(26±1.5)%。异烟肼-聚乳酸-羟基乙酸微球平均粒径(250±10)μm,载药率为(28±1.8)%。利福平、异烟肼,90 d体外累积释放率可达到80%和90%。90 d体内释放利福平和异烟肼的浓度可达(0.5±0.4)和(0.6±0.3)μg/g。缓释双药物载体置入兔股骨转子间骨缺损部位可见筋膜、肌纤维之间出现少量中性粒细胞浸润,59 d 后肌肉组织中性粒细胞明显减少,X射线平片显示骨缺损明显缩小。提示该载体能够长时间保持骨结核周围组织中一定的药物浓度,弥补血中药物浓度不足,有望在骨结核手术治疗中提供一种新型的双药物缓释载体。     

成骨生长肽壳聚糖—海藻酸钠微球的制备及体外检测

背景:成骨生长肽体外注射可以刺激外周血和骨髓细胞数增加,增加动物的骨量,加速骨折愈合,但因多肽不稳定性及注射应用不方便,限制了其临床应用。目的:应用乳化交联法制备成骨生长肽壳聚糖-海藻酸钠缓释微球,并对其粒径、载药、体外释药、理化特性进行检测。方法:以戊二醛作为交联剂,应用乳化交联法制备具有控制释放功能的负载成骨生长肽壳聚糖-海藻酸钠微球,显微镜及扫描电镜观察微球的形态和粒径;利用酶联免疫吸附实验动态检测成骨生长肽壳聚糖-海藻酸钠微球的载药率、包封率和缓释规律。结果与结论:乳化交联法制备的壳聚糖-海藻酸钠微球,球形良好,球体表面有较多微孔,具有较高的包封率(>72%)。体外药物释放实验表明,成骨生长肽可以从壳聚糖-海藻酸钠微球中缓慢释放,整个释放过程可达49d,累积释放率>85%。提示应用乳化交联法制备的负载成骨生长肽壳聚糖-海藻酸钠缓释微球,具有很好的控制释放成骨生长肽的能力。     

聚乙二醇对利福平-聚乳酸-羟基乙酸聚合物缓释微球性能的影响

背景：聚乳酸-羟基乙酸共聚物微球具有良好的生物相容性,是优良的药物缓释载体,但缓释微球的突释问题严重影响了其临床应用。
　　目的：观察聚乙二醇对利福平-聚乳酸-羟基乙酸聚合物缓释微球特征、载药率、包封率、体外释放规律及突释的影响。
　　方法：以高分子材料聚乳酸-羟基乙酸共聚物作为载体,采用复乳化-溶剂挥发法制备聚乙二醇-利福平-聚乳酸-羟基乙酸聚合物微球(实验组)和利福平-聚乳酸-羟基乙酸聚合物微球(对照组)。扫描电子显微镜观察两组聚合物缓释微球特征,高效液相色谱法检测两组微球在不同时段模拟体液中的利福平药物浓度及累计释放量,计算两组微球的载药量、包封率。
　　结果与结论：与对照组比较,实验组微球表面光滑、粒径减小、分散良好,包封率和载药量明显提高。实验组微球3 h内药物释放量最大,1 d左右药物释放趋于平稳稳定状态,1 d药物累计释放量小于20%;对照组微球3 h内药物释放量最大,约为实验组的1.5倍,1 d左右药物释放也趋于平稳状态。表明聚乙二醇可改善利福平-聚乳酸-羟基乙酸聚合物缓释微球的成球率,减小其粒径,增加其载药量和包封率,控制其突释现象。     

聚羟基丁酸-羟基辛酸共聚酯载生长因子的缓释纳米微球

背景：骨形态发生蛋白2可增加软骨细胞和祖细胞基质的产生,可增强组织金属蛋白酶抑制因子1、sox9基因、Ⅱ型胶原以及聚集蛋白聚糖的表达,具有诱导间充质细胞迁徙、增殖、分化,最终促使软骨、骨形成的作用。目的：制备重组人骨形态发生蛋白2聚羟基丁酸-羟基辛酸共聚酯纳米微球系统纳米微球缓释系统,观察微球生长因子形态和粒径分布、载药量、包封率、体外缓释时间及生物活性。方法：采用复乳-干燥法制备重组人骨形成蛋白2聚羟基丁酸-羟基辛酸共聚酯纳米微球系统,体外分离培养猪软骨细胞。实验分为3组：第1组培养液不添加药物做为对照;第2组培养液中添加含20μg/L重组人骨形态发生蛋白2;第3组培养液中添加20μg/L重组人骨形态发生蛋白2聚羟基丁酸-羟基辛酸共聚酯纳米微球系统纳米微球;其中在第2组和第3组又将重组人骨形态发生蛋白2和重组人骨形态发生蛋白2聚羟基丁酸-羟基辛酸共聚酯纳米微球系统纳米微球分别设为55,100μg/L两种的有效浓度,采用MTT法检测微球对软骨细胞增殖的影响,模拟体内条件观察纳米微球的体外缓释性及生物活性。结果与结论：该纳米微球表面光滑圆整,球体大小均匀,粒径为231-415 nm,扫描电镜平均粒径323 nm。微球的包封率和载药量分别为（79.63＆#177;0.16）%和（1.92＆#177;0.16）%。根据15 d内对重组人骨形态发生蛋白2聚羟基丁酸-羟基辛酸共聚酯纳米微球的体外释药的观察,保持持续释放重组人骨形态发生蛋白2,且释放的浓度呈增长水平。该微球缓释系统有生物活性,能显著促进猪软骨细胞的增殖,其效应高于单纯重组人骨形态发生蛋白2的效应。提示重组人骨形态发生蛋白2聚羟基丁酸-羟基辛酸共聚酯纳米微球缓释系统包封率、载药量、体外释药性以及生物活性符合纳米微球的一般?     

成骨生长肽缓释微球促成骨细胞的增殖

背景:采用生物可降解聚合物聚乳酸-羟基乙酸共聚物(Polylactide-co-glycolide,PLGA)为支架材料,包裹多肽、蛋白质药物制成缓释微球,使在体内达到缓释目的,是近10多年来各国学者大力研究的新领域。目的:观察成骨生长肽(osteogenic growth peptide,OGP)缓释微球对成骨细胞的促分裂增殖作用。设计、时间及地点:对比观察,于2006-06/11在西安交通大学生命科学院完成。材料:新西兰兔,用于制备成骨细胞;PLGA由山东医疗器械研究所提供。方法:以PLGA为载体材料,采用复乳法制备OGP-PLGA缓释微球,并对微球的形态学、粒径分布、载药量和包裹率及体外释药情况进行观察。实验分为2组,OGP组:培养液为含体积分数0.1小牛血清 含50μg/LOGP的DMEM;OGP缓释微球组:培养液为含体积分数0.1小牛血清 含50μg/LOGP-PLGA缓释微球的DMEM,分别测定成骨细胞的增殖数量。主要观察指标:①微球的形态、粒径分布、载药量、包裹率及体外释药性。②OGP缓释微球对成骨细胞增殖的影响。结果:①复乳法制备的OGP-PLGA缓释微球表面光滑圆整,球体均匀度好;微球粒径为(19.6±4.47)μm,载药量和包裹率分别为(83.9±4.21)%,(72.9±5.13)%;微球的体外释药过程较为稳定,56d释药率为85.43%。②培养1,2d时,OGP组的A值高于OGP缓释微球组,差异有显著性意义(P<0.05);培养3,4d时,OGP组和OGP缓释微球组间A值差异无显著性(P>0.05);培养6,8d时,OGP缓释微球组的A值高于OGP组,差异有显著性意义(P<0.05)。结论:采用复乳法制备OGP-PLGA缓释微球的工艺可行,微球中OGP的生物活性保存良好,能缓慢持续释放活性OGP,促进成骨细胞的体外分裂增殖。     

转化生长因子β1缓释壳聚糖微球制备及体外的细胞相容性

背景:利用缓释系统释放生长因子,是目前生物活性因子应用研究的方向之一.目的:应用离子交联沉淀法制备壳聚糖-转化生长因子β1缓释微球,观察其体外缓释性能以及细胞相容性.设计、时间及地点:观察性实验,于2006-10/2007-09在华中科技大学同济医学院附属协和医院中心实验室完成.材料:壳聚糖,脱乙酰度90%,由清华人学化学工程系提供:转化生长因子β1,由晶美公司提供;大鼠由华中科技大学同济医学院实验动物中心提供.方法:①离子交联沉淀法制各壳聚糖微球,并包裹转化牛长因子β1,制备可体外缓释转化生长因子β1 的壳聚糖-转化生长因子β1缓释微球.②选择传代二三次、生长良好的大鼠胸降主动脉中层肌成纤维细胞,调节细胞密度至1 × 108 L-1,分别加入不同浓度(4,2,1 g/L)壳聚糖微球浸提液,不含浸提液的培养基作为对照培养.主要观察指标:扫描电镜、激光粒度分析仪、Elisa法观察微球表面形态,测定药物载药率、包封率、体外缓释效率等指标:阳甲基偶氮唑盐法观察细胞增殖情况,评估壳聚糖微球体外细胞相容性.结果:所得微球球形良好.表面光滑,粒径分布集中,平均粒径272 nm.壳聚糖微球有较高的药物包封率,达80.60%.体外释放试验提示,转化生长因子β1初期存在突释现象,前24 h释放达27%,其后可从壳聚糖微球中稳定释放,7 d累计释放达41%.四甲摹偶氮唑盐法提示该壳聚糖微球对细胞体外生长无不良影响,相容性好.结论:离子交联沉淀法制备壳聚糖缓释微球方法简单易行,所得壳聚糖-转化生长因子β1微球具有良好的缓释效能及细胞相容性.     

重组人骨形态发生蛋白2缓释微球的制备与评价

目的：针对重组入骨形态发生蛋白2（recombinant human bone morphogenetic protein-2，rhBMP-2）在体内半衰期短、易被稀释代谢的问题，探讨利用聚乳酸-羟基乙酸共聚物（PLGA）制备载rhBMP-2微球的可行性和制备工艺，并观察其载药、释药特性。方法：①采用W／O／W型复乳化-溶剂挥发技术制备rhBMP-2／PLGA缓释微球，并对微球的粒径和形态、包封率和载药量，体外释放性质进行测定。②异位成骨实验：昆明小鼠12只，在右侧大腿股内侧肌袋内植入含rhBMP-2的50mgPLGA微球，4周后取材，观察成骨情况以初步检测微球中的蛋白质活性。结果：①rhBMP-2／PLGA缓释微球形态良好，粒径主要集中在50—60μm，包封率为（37．52±4．31）％，载药率为（5．12±1．32）％。②微球的释放存在突释，7d内释放的药物量超过40％，大约90％的药物量于42d内释放完全。③载药微球植入鼠股部肌袋4周，材料周围有明显的骨形成。结论制备的rhBMP-2／PLGA微球可以缓慢释放有活性的rhBMP-2，具有临床应用的可行性。     

Preparation, characterization and in vitro release of gentamicin from PHBV/wollastonite composite microspheres.

Composite microspheres have been prepared from bioactive wollastonite (W) and biodegradable poly (hydroxybutyrate-polyhydroxyvalerate) (PHBV) in the present study. Gentamicin was encapsulated into the microspheres by the absorption method and the in vitro release of the gentamicin from the microspheres was performed in distilled water, modified simulated body fluid (SBF) and phosphate buffered saline (PBS) at 37 degrees C for 22 days, respectively. The results showed that the release behavior of gentamicin from PHBV/W composite microspheres was similar to that from the pure PHBV microspheres when the experiment was performed in distilled water. However, in the PBS and SBF solutions, gentamicin released from the PHBV/W composite microspheres at a relatively lower rate as compared to that of the pure PHBV microspheres and 90% of the total amount of gentamicin released from the composite microspheres after soaking for 22 days, which was much longer than that for the release of the same amount gentamicin from the pure PHBV microspheres (8 days). Scanning electron microscopy (SEM) and energy-dispersive spectrometer (EDS) analysis on the microspheres after release in SBF and PBS revealed that a microporous apatite layer was formed on the composite microspheres surface, which resulted in a controlled release behavior of the gentamicin from the PHBV/W composite microspheres. All of these results provided the possibility that the PHBV/W composite microspheres could be applied as alternative drug controlled release systems, especially as bone fillings for bone repair due to their advantages of controlled releasing antibiotics and apatite-formation ability, through which the implanted microspheres could chemically bond to the surrounding tissue in vivo.     

Synchronic release of two hormonal contraceptives for about one month from the PLGA microspheres: In vitro and in vivo studies

A controlled drug release system based on the injectable PLGA microspheres loaded with gestodene and ethinyl estradiol was prepared and evaluated for the feasibility of monthly synchronic delivery of the two hormonal contraceptives. The scanning electron microscopy, light-scattering analyzer and gel permeation chromatography were used to study the morphology, particle size and molecular weight of the polymer microspheres, respectively. HPLC was utilized to determine the drug loading and the drug released, while a LC-MS-MS system was employed to analyze the plasma drug concentration. Result indicated that the PLGA particles obtained were spherical and appropriate in size. The formulation was stable during the test period. In vitro drug release from the microspheres for both drugs was sustained for about 30 days mostly by the diffusion mechanism. The plasma drug concentration-time profiles of the drug-loaded microspheres were relatively smooth after subcutaneous injection to rats for about 1-month, compared with that for drug suspension. In vitro and in vivo correlation was established. One of the most important facts is the synchronicity of the two contraceptives both in the release kinetics in vitro and the pharmacokinetic behaviors in vivo. Therefore, the synchronic delivery of two contraceptives is achieved for about 1 month by using the injectable PLGA-based microspheres.     

Preparation and in vitro and in vivo release studies of Huperzine A loaded microspheres for the treatment of Alzheimer's disease.

The purpose of this study was to prepare microspheres containing Huperzine A, which is used for patients suffering from Alzheimer's disease because of its potent anticholineestase activity, and to clarify in vitro and in vivo release characteristics of them. The preparation and in vitro and in vivo release studies of Huperzine A loaded microspheres were described. By spray drying method, Huperzine A was encapsulated successfully in the microspheres which were spherical with a non-porous and smooth surface. In vitro studies showed that the release of Huperzine A from microspheres was depended on the properties of polymers and the release medium. Counter-ionic interaction between the primary amine group of Huperzine A and the carboxylic terminal group of PLG polymers improves the encapsulation of Huperzine A, reducing the initial burst and extending the sustained release. High molecular weight of PLG polymer leads to a negative influence on sustained release of Huperzine A due to less carboxylic terminal groups. Acidic medium also reduces the initial burst and sustained the release due to decreased swelling of the polymeric matrix. In vivo experiment showed, after intramuscular injection, that the plasma concentration of Huperzine A reached the max. at 2 h, then fell rapidly to a stable and near constant level of 0.5 to 2.5 ng/ml within 2 weeks, until the drug was exhausted from the microspheres. It indicates the potential of a 2-week sustained release system of Huperzine A.     

全反式维甲酸-聚酸酐长效缓释剂研制及其可行性

背景：如何提高全反式维甲酸疗效、稳定性和降低毒副作用是临床治疗所面临的最大问题。近年来用可生物降解的聚合物为材料,通过乳化包囊等分散技术将药物制备成微粒分散体系,用作缓释、控释注射剂的研究日益增多。目的：研制全反式维甲酸-聚酸酐长效缓释微球肿瘤治疗剂,观察其体内外全反式维甲酸经时缓释变化规律。方法：采用乳剂-扩散溶剂挥发法制备全反式维甲酸-聚酸酐长效缓释微球肿瘤治疗剂,扫描电镜检测微球外观及微球粒径,高效液相色谱法检测微球载药量、包封率及体内外释药量。结果与结论：所制微球治疗剂光滑圆整,大小均一,平均粒径（154.42±26.76）nm,载药率（16.5±1.45）%,包封率（87.84±4.79）%;体外释放实验证明该微球治疗剂可持续释放全反式维甲酸约50d,将其肌肉注射到大耳白兔体内,可稳定缓释全反式维甲酸近45d。结果表明该微球治疗剂载药量及包封率均较高,体内外释药平稳并且具有明显的长效缓释作用。     

A new approach to the in vivo and in vitro investigation of drug release from locoregionally delivered microspheres.

The purpose of this work was to determine the in vivo release profile of doxorubicin (Dox) delivered locoregionally by dextran-based microspheres (MS) and to develop an in vitro method for predicting in vivo drug release from MS-- in vitro-in vivo correlation (IVIVC). For the determination of in vivo Dox release, drug-loaded MS were placed into hollow fibers (HF) and implanted subcutaneously into C3H mice. Samples were retrieved at various times following implantation, MS removed from HF, and the amount of Dox remaining determined via ultraviolet/visible (UV/Vis) spectrophotometry. Various in vitro systems were designed and investigated for their ability to link in vivo and in vitro release profiles, including an open system (e.g. a column) with continuous flow of release medium at different flow rates and closed systems (e.g. a cuvette) using different release media and conditions. About 34% of loaded Dox was released from MS in vivo at 48 h. Only an incremental release was observed over the ensuing 72 h. The release kinetics of Dox from MS using three of the investigated in vitro systems, column system and HF immersed in a buffer solution or growth medium gave release profiles that were highly correlated with the in vivo release profile (r(2)>0.9). The relationships, both linear and non-linear, suggest that Level A IVIVC models can be developed for Dox release from locoregionally delivered MS using specially designed release systems.     

全反式维甲酸-聚酸酐长效缓释剂研制及其可行性

背景:如何提高全反式维甲酸疗效、稳定性和降低毒副作用是临床治疗所面临的最大问题。近年来用可生物降解的聚合物为材料,通过乳化包囊等分散技术将药物制备成微粒分散体系,用作缓释、控释注射剂的研究日益增多。目的:研制全反式维甲酸-聚酸酐长效缓释微球肿瘤治疗剂,观察其体内外全反式维甲酸经时缓释变化规律。方法:采用乳剂-扩散溶剂挥发法制备全反式维甲酸-聚酸酐长效缓释微球肿瘤治疗剂,扫描电镜检测微球外观及微球粒径,高效液相色谱法检测微球载药量、包封率及体内外释药量。结果与结论:所制微球治疗剂光滑圆整,大小均一,平均粒径(154.42±26.76)nm,载药率(16.5±1.45)%,包封率(87.84±4.79)%;体外释放实验证明该微球治疗剂可持续释放全反式维甲酸约50d,将其肌肉注射到大耳白兔体内,可稳定缓释全反式维甲酸近45d。结果表明该微球治疗剂载药量及包封率均较高,体内外释药平稳并且具有明显的长效缓释作用。     

聚乳酸羟基乙酸/纳米羟基磷灰石-5-氟尿嘧啶复合微球的制备及体外释放

背景:由聚乳酸羟基乙酸/纳米羟基磷灰石复合材料制备的微球,在体外磷酸盐缓冲液中能够持续释放药物.目的:制备聚乳酸羟基乙酸/纳米羟基磷灰石-5-氟尿嘧啶复合微球,探讨纳米羟基磷灰石对复合微球的载药量、包封率和体外释放等性质的影响.设计、时间及地点:材料学体外观察,于2009-02/2009-07在华南理工大学材料学院实验室完成.材料:聚乳酸羟基乙酸为济南岱罡生物有限公司产品,纳米羟基磷灰石由华南理工大学特种功能材料教育部重点实验室自制,5-氟尿嘧啶为上海楷洋生物技术有限公司产品.方法:以水溶性抗癌药物5-氟尿嘧啶作为模型药物,先用纳米羟基磷灰石吸附药物,外包裹生物相容性好且可生物降解的聚乳酸羟基乙酸,采用单乳化溶剂挥发法(S/O/W)制备聚乳酸羟基乙酸,纳米羟基磷灰石-5-氟尿嘧啶复合微球.对载药前后的纳米羟基磷灰石进行透射电子显微镜、扫描电子显微镜观察和FTIR分析.采用扫描电镜、激光粒度仪和紫外分光光度计对微球的理化性质及体外释药性质进行分析.主要观察指标:纳米羟基磷灰石与5-氟尿嘧啶分子之间的相互作用,微球载药量和包封率,药物体外释放.结果:FTIR结果表明,纳米羟基磷灰石对5-氟尿嘧啶有较强的吸附作用.聚乳酸羟基乙酸/纳米羟基磷灰石-5-氟尿嘧啶复合微球的载药量和包封率分别为3.83%,86.78%,明显高于单纯的聚乳酸羟基乙酸-5-氟尿嘧啶微球.经过体外释放药物突释后,复合微球比单纯聚乳酸羟基乙酸微球的药物释放慢.在第27天,复合微球和单纯的聚乳酸羟基乙酸微球累积药物释率放分别为84.87%,99.87%.结论:与单纯的聚乳酸羟基乙酸-5-氟尿嘧啶微球相比,由于纳米羟基磷灰石对5-氟尿嘧啶存在较强的吸附作用,使聚乳酸羟基乙酸/纳米羟基磷灰石-5-氟尿嘧啶复合微球的载药量和包封率得到了较大提高,具有更好的药物缓释效果.