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49 d,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。     

制备壳聚糖微球体外缓释TGF-β_1的研究

应用离子交联沉淀法制备壳聚糖-转化生长因子（TGF-β1）缓释微球,研究其体外缓释性能。采用离子交联沉淀法制备壳聚糖微球,以其包裹TGF-β1,制备具有缓释效能的壳聚糖-TGF-β1缓释微球。用扫描电镜、激光粒度分析仪、Elisa法等观察其表面形态,测定药物载药率、包封率、体外缓释效率等指标。结果表明：所得微球球形良好,表面光滑,粒径分布集中,平均粒径272nm。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,TGF-β1初期存在突释现象,前24h释放达27%,但其后可从壳聚糖微球中稳定释放,7d累计释放达41%。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-TGF-β1微球具有良好的缓释效能,提示其在组织工程领域具有良好的应用前景。     

制备壳聚糖微球体外缓释TGF-β1的研究

应用离子交联沉淀法制备壳聚糖-转化生长因子（TGF-β1）缓释微球,研究其体外缓释性能。采用离子交联沉淀法制备壳聚糖微球,以其包裹TGF-β1,制备具有缓释效能的壳聚糖-TGF-β1缓释微球。用扫描电镜、激光粒度分析仪、Elisa法等观察其表面形态,测定药物载药率、包封率、体外缓释效率等指标。结果表明：所得微球球形良好,表面光滑,粒径分布集中,平均粒径272nm。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,TGF-β1初期存在突释现象,前24h释放达27%,但其后可从壳聚糖微球中稳定释放,7d累计释放达41%。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-TGF-β1微球具有良好的缓释效能,提示其在组织工程领域具有良好的应用前景。     

强的松龙纳米微球缓释膜制备及缓释特性

背景:近年来将强的松龙应用于促进周围神经损伤后功能恢复取得了良好效果,但因半衰期短、局部应用血药浓度不稳定及较大的不良反应限制了其临床应用。目的:制备强的松龙纳米微球缓释膜并对其药物缓释特性进行检测。方法:采用反胶束乳化溶剂挥发法制备强的松龙纳米微球,对载药纳米微球的形态、粒径、载药量、包封率和体外释药行为等性质进行研究;同时将纳米微球与胶原、壳聚糖、大豆卵磷脂等膜材相结合,制得复合药膜,考察复合药膜的形貌、膜中材料的相互作用及药膜的体外释药行为。结果与结论:强的松龙纳米微球具有良好的微观结构,药物均匀分布于纳米微球中,纳米微球粒径均一,表面光滑,平均粒径500 nm,包封率达90%以上,体外缓释实验药物释放良好,存在一定的药物突释现象。观察球膜结合方法制得的复合膜,可见纳米微球均匀分散于复合膜中,复合膜微观结构良好,体外缓释实验见复合膜药物释放更加稳定,无明显药物突释现象出现,显示了良好的药物释放效果。表明通过反胶束乳化溶剂挥发法和球膜结合方法制备出的强的松龙缓释膜剂具有良好的药物缓释特性。     

壳聚糖微球包裹幽门螺杆菌全菌蛋白抗原的制备及体外释放性能

背景：包裹幽门螺杆菌全菌蛋白抗原的研究仍处于探索阶段,有关壳聚糖微球包裹幽门螺杆菌全菌蛋白抗原的制备工艺及体外释放性能的文献甚少。 目的：探讨幽门螺杆菌全菌蛋白抗原壳聚糖微球的制备工艺及体外释放特性。 方法：采用沉淀法制备壳聚糖微球,筛选最佳制备工艺及配比、包裹时间,并在电镜下观察微球的形态和粒径。采用壳聚糖微球包裹幽门螺杆菌全菌蛋白抗原,BCA法测定幽门螺杆菌全菌蛋白抗原微球的包裹率、包裹量及体外释放率。 结果与结论：终体积分数为1%的冰醋酸、硫酸钠为交联剂、pH 5.0、滴加交联剂时不粉碎处理为壳聚糖微球最佳制备工艺,电镜观察显示微球表面光滑、形态圆整,具有良好的分散性,多数微球粒径为1.0-5.0 μm。幽门螺杆菌全菌蛋白抗原微球的包裹率为80.4%,包裹量为16.4%,48 h总释放率为19.4%,幽门螺杆菌全菌蛋白抗原微球整体呈缓慢释放状态。结果证实,实验制备的壳聚糖微球对幽门螺样菌全菌蛋白抗原具有良好的包裹率和包裹量,幽门螺杆菌全菌蛋白抗原微球整体呈缓慢释放状态。中国组织工程研究杂志出版内容重点：生物材料;骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性;组织工程      

重组人骨形态发生蛋白2壳聚糖纳米微球的制备及体外细胞毒性

背景：通过各种微球负载骨生长因子使骨形态发生蛋白达到缓释效果逐渐成为研究热点,但关于载药壳聚糖纳米微球的生物相容性特别是细胞毒性的报道较少。 目的：对重组人骨形态发生蛋白2壳聚糖纳米微球进行细胞毒性检测,评估应用壳聚糖纳米微球作为重组人骨形态发生蛋白2缓释载体的生物安全性。 方法：通过离子交联法制备空白壳聚糖纳米微球,应用透视电镜观察微球的形态,激光粒径分析其粒径分布;通过重组人骨形态发生蛋白2壳聚糖纳米微球体外细胞毒性试验评估微球的生物安全性。 结果与结论：离子交联法制备的壳聚糖微球,球形规整,分散均匀,微球平均粒径为230 nm,分布较集中。载药及空白微球的反应分级为0或1级,均为合格。提示,离子交联法制备可成功制备出负载重组人骨形态发生蛋2的纳米微球,且微球细胞毒性检测合格,为进一步的骨组织工程研究提供理论实验基础。     

交联明胶材料制备及细胞毒性的实验研究

目的:制备交联明胶,并检测其微球物理性质和细胞毒性。方法:采用双相乳化冷凝聚合法制备交联明胶,采用光镜和扫描电镜观察微球外形和分散度,紫外分光光度法测绘交联明胶体外戊二醛释放曲线,MTT实验检测其细胞毒性。结果:所制备的交联明胶微球表面光滑、直径均匀,干粉微球直径为21.13±1.42μm,溶胀后为26.72±1.74μm,溶胀率为127%。戊二醛释放实验和MTT实验证明其无细胞毒性。结论:交联明胶微球能在体外缓释超过30天,能有效吸附溶液、细胞毒性低,是下一步以交联明胶为载体进行基因转染实验的基础。     

海藻酸盐控释微球的制备及其体外释药特性

研制白蛋白海藻酸钠(BSA-海藻酸钙微球)控释微球,并对其体外释药特性等进行考察,为应力控释VEGF促进组织工程骨血管化提供理论依据。以海藻酸钠为载体,采用W/O乳化-离子交联法制备BSA-海藻酸钙微球;检测粒径大小、外观、包封率等理化特性;考察微球的体外释药特性。微球球形圆整,分散性好,平均粒径为230±60μm,载药量达80.3μg/mg,包封率为61%;微球的体外释药速率平稳,周期达2周余。海藻酸钠可以作为蛋白、多肽类药物的可生物降解辅料;乳化离子交联法的制备工艺简便,有利于蛋白、多肽类药物结构和功能的稳定性并有效延长其作用时间。     

壳聚糖微球/纳米羟基磷灰石/聚乳酸-羟基乙酸复合支架制备及其蛋白缓释效果:与单纯纳米羟基磷灰石/聚乳酸-羟基乙酸支架、壳聚糖微球的比较

背景:骨组织工程骨构建中如何使生长因子持续高效发挥作用是影响成骨速度和质量的关键,现多以各种材料的微球或支架作为缓释载体,但缓释作用有待提高。目的:实验拟制备壳聚糖微球,然后复合到纳米羟基磷灰石/聚乳酸-羟基乙酸支架上,形成双重缓释作用,并测量对牛血清白蛋白的释放效果。方法:以牛血清白蛋白为模型药物,采用乳化交联法制备壳聚糖微球。将微球与纳米羟基磷灰石、聚乳酸-羟基乙酸按一定比例混合,以冰粒子为致孔剂,采用冷冻干燥法制备壳聚糖微球/纳米羟基磷灰石/聚乳酸-羟基乙酸复合支架。利用扫描电镜、激光粒度分析仪、压泵仪和力学性能测试仪检测复合支架的形态性能,考察药物在缓释支架上的体外释放规律。结果与结论:所制备的壳聚糖微球形态良好,呈规则圆球形,粒径集中分布在20～40μm,微球药物包封率为86.5%,载药量为0.8%,随牛血清白蛋白初始用量的增加,载药量可升高至2.6%,但包封率下降至74.1%。壳聚糖微球能均匀分布在聚乳酸-羟基乙酸支架上,形成壳聚糖微球/纳米羟基磷灰石/聚乳酸-羟基乙酸复合支架,孔径为100～400μm,孔隙率80%,压缩强度为1.1～2.3MPa,10周降解率为26.5%。单纯纳米羟基磷灰石/聚乳酸-羟基乙酸支架其牛血清白蛋白在36h累积释放量达85%以上,壳聚糖微球其牛血清白蛋白10d累积释放量为33.6%,复合支架其牛血清白蛋白40d累积释放量为81.5%。结果证实包埋壳聚糖微球的纳米羟基磷灰石/聚乳酸-羟基乙酸支架其压缩强度和降解速率合适,对蛋白类药物具有良好的缓释作用,有望作为组织工程的支架材料和生长因子的缓释载体。     

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45 d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,24 h释放20%左右,45 d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28 d内缓慢升高,其后缓慢下降,持续56 d以上,浓度38.50~155.75 µg/g;对照组异烟肼浓度在1周左右达高峰,为1982.5 µg/g,21 d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。     

膜乳化法制备单分散性载羟基喜树碱缓释微球

目的 研究利用微孔膜乳化法制备载抗癌药10-羟基喜树碱（IqCPT）缓释微球的可行性。方法 以HCPT为模型药物,聚乳酸（PEA）为载体,以膜乳化法制备载药微球,并研究制剂的表面形态、载药率、包封率和缓释效果等性质。结果 膜乳化法制备的载HCPT聚乳酸微球,粒径可控制在1-10μm之间。表面圆整,稳定性、单分散性良好,载药率和包封率最高分别可达32．7％和81．7％,24h体外累积释放量为17．3％。结论 膜乳化法制备的载HCPT微球制剂均匀分散,具有明显缓释效果,是制备缓释微球制剂的较好方法。     

Development of an injectable two-phase drug delivery system for sequential release of antiresorptive and osteogenic drugs

Unlike controlled release systems that deliver a single drug, dual or multidrug delivery systems with distinct release profiles are more likely to promote timely and effective tissue regeneration as they provide both temporally and concentration-dependent release of different molecules to mimic natural biological events. In this study, an injectable and biodegradable delivery system was developed to sequentially release an antiresorptive drug (clodronate) followed by an osteogenic agent (simvastatin) to treat bone disease. The injectable delivery system comprised simvastatin-loaded gelatin microspheres suspended in a viscous solution of carboxymethylcellulose (CMC) containing clodronate. Several factors (CMC concentration, glutaraldehyde concentration, simvastatin loading, and gelatin microsphere processing conditions) were investigated for their effects on drug release. Clodronate release was not affected by CMC concentration, with complete delivery within 12 hr, and simvastatin release could be modulated by cross-linking of the gelatin microspheres, loading, and washing conditions. Burst release of simvastatin was reduced from 70% to 6% in conjunction with sustained release for up to 3 weeks. The combined system showed early release of the antiresorptive clodronate sequentially followed by sustained delivery of the osteogenic simvastatin. This robust and flexible two-phase delivery system may prove useful for applications in which multiple drug delivery is desired.     

Study on Preparation and Release of Dexamethasone Hyaluronan Microspheres

Hyaluronan （HA） , the consistent glycosaminoglycans in extracellular matrix, is a kind of biomaterials with wonderful biocompatibility. To develop drug release system （DDS） with HA as drug carrier is a new hotspot in the field of pharmaceutics. In this paper, we applied technique of ultrosound and reversed phase （Water/Oil） emulsification to develop dexamethasone （DEX）-HA-STMP cross-linking microspheres （DEX-HA MS） with STMP as cross-linker. DEX-HA MS has a wonderful shape and property of dispersion. There is a negative correlation between diameter of DEX-HA MS and the content of cross-linker, or the content of emulsifier, and a positive correlation between the diameter and CHA. When CHA ≤ 1% ,DEX/HA≤ 1/10 （g/g） ,there is a positive correlation between the factors mentioned below and drug loading （ DL% ）/loading efficiency （ LE% ）, the content of STMP, the content of emulsifier, CHA and the content of DEX. DEX-HA-MS can realize function of slow release. In vitro drug release experiment shows that cumulative release （CR%） of DEX-HA MS fits in with pervasion-corrosion equation, and there is a negative correlation between the content of STMP, CHA and CR%, a positive correlation between emulsifier and CR%. When DEX/HA ≤ 1/5 （g/g） there is a negative correla- tion between the content of DEX and CR%.     

Preparation and in vitro release of curcumin sustained-release microspheres北大核心

BACKGROUND: Curcumin can inhibit inflammation and promote axonal growth, but it has a short half-life and a fast clearance rate. OBJECTIVE: To prepare curcumin sustained-release microspheres to release curcumin slowly and continuously. METHODS: Curcumin sustained-release microspheres were synthesized by O/W emulsification volatilization method using polylactic acid-glycolic acid copolymer as raw material. The preset drug loading rates were 10% and 20%, respectively, and set as No. 1 and No. 2 microspheres. The curcumin sustained release microspheres were synthesized by O/W emulsification volatilization method using L-lactic acid-polycaprolactone copolymer as raw material. The preset drug loading rates were 10% and 20%, respectively, and the microspheres were set as No. 3 and No. 4. The surface morphology of the microspheres was observed by scanning electron microscopy, and the drug loading and encapsulation efficiency of the microspheres were determined by high performance liquid chromatography. Four groups of microspheres were immersed in PBS release solution containing 1% sodium dodecyl sulfate, and the sustained release of curcumin microspheres was detected under simulated physiological environment. RESULTS AND CONCLUSION: (1) Scanning electron microscopy showed that the particle size and morphology of No. 3 and No. 4 curcumin microspheres were better than those of No. 1 and No. 2 curcumin microspheres. (2) The encapsulation rate of No. 3 microspheres was higher than that of the other three groups (P < 0.05, P < 0.01), and there was no significant difference in the encapsulation rate of No. 1, 2 and 4 microspheres (P > 0.05). (3) The drug loading rates of No. 2, 3 and 4 microspheres were higher than that of No. 1 microsphere (P < 0.01), and the drug loading rates of No. 2 and 4 microspheres were higher than that of No. 3 microsphere (P < 0.01). (4) The in vitro release of No. 3 curcumin sustained-release microspheres lasted for 14 days, and the release of the other three kinds of microspheres lasted for 21 days. The cumulative release rate of No. 1 and No. 3 was higher than that of No. 2 and No. 4, and the curcumin release concentration of No. 3 was higher than that of No. 1. (5) The results showed that slow-release effect of the curcumin sustained-release microspheres with a preset loading rate of 10% prepared by L-lactic acid-polycaprolactone copolymer best meets the Zero order release requirements. © 2022, Publishing House of Chinese Journal of Tissue Engineering Research. All rights reserved.     

5-氟尿嘧啶缓释剂制备及体外释药性能比较*

背景：5-氟尿嘧啶-聚乳酸-乙醇酸共聚物缓释微球在青光眼滤过术后抑制滤过泡的瘢痕化具有潜在应用价值,但微球制备程序复杂,微球载药量一般较低,且药物突释现象明显。 目的：比较乳化溶剂挥发法制备的5-氟尿嘧啶-聚乳酸-乙醇酸共聚物微球和喷雾成膜法制备的5-氟尿嘧啶-聚乳酸-乙醇酸共聚物缓释膜两种缓释剂的形态、载药量、体外释放规律,以探讨获得缓释效果较佳的5-氟尿嘧啶缓释剂制备方法。 方法：以聚乳酸-乙醇酸共聚物为载体,采用乳化溶剂挥发法制备5-氟尿嘧啶-聚乳酸-乙醇酸共聚物微球;用喷雾成膜法制备5-氟尿嘧啶-聚乳酸-乙醇酸共聚物缓释膜。 结果与结论：用乳化溶剂挥发法制备的微球外观圆整,粒径为(4 447.4±359.8) nm,载药量(8.67±0.37)%,包封率为(86.68± 1.92)%;用喷雾成膜法制备的缓释膜表面光滑平整,质量为(13.76±0.26) mg ,直径为6 mm ,厚度为(0.24±0.005) mm,载药量(23.76±0.37)%,包封率为(95.04±1.36)%。缓释剂制备过程未影响5-氟尿嘧啶的药物性能。微球体外释放突释明显,缓释膜的体外释放平稳持久,释放曲线符合Higuchi方程。结果表明缓释膜制备方法更简单易行,且能明显提高缓释剂的载药量,降低突释现象,同时延长药物的缓释时间。 关键词：聚乳酸-聚乙醇酸;5-氟尿嘧啶;微球;缓释膜;体外释放 doi:10.3969/j.issn.1673-8225.2012.08.022     

Controlled release of antihypertensive drug from the interpenetrating network poly(vinyl alcohol)-guar gum hydrogel microspheres

Poly(vinyl alcohol)-guar gum interpenetrating network microspheres were prepared by cross-linking with glutaraldehyde. Nifedipine, an antihypertensive drug, was loaded into these matrices before and after cross-linking to study its release patterns. The extent of cross-linking was analyzed by Fourier transform infrared spectroscopy and differential scanning calorimetry. Furthermore, the microspheres were characterized for drug entrapment efficiency, particle size, transport of water into the matrix and drug release kinetics. Scanning electron microscopic photographs confirmed the spherical nature and surface morphology. The mean particle size of the microspheres was found to be around 300 microm. The molecular transport phenomenon, as studied by the dynamic swelling experiments, indicated that an increase in cross-linking affected the transport mechanism from Fickian to non-Fickian. The in vitro release study indicated that the release from these microspheres is not only dependent upon the extent of cross-linking, but also on the amount of the drug loaded as well as the method of drug loading.     

Neovascularization effect of biodegradable gelatin microspheres incorporating basic fibroblast growth factor

Biodegradable microspheres were prepared through glutaraldehyde cross-linking of gelatin without using any surfactants as a carrier matrix of basic fibroblast growth factor (bFGF). In the in vitro system, bFGF was sorbed to microspheres of acidic gelatin with an isoelectric point (IEP) of 5.0, but not to those of basic gelatin with an IEP of 9.0. The rate of bFGF sorption to the acidic gelatin microsphere in phosphate-buffered saline solution (pH 7.4) was smaller than that in water. Following incorporation of bFGF into the microspheres at 4 degrees C for 12 h, bFGF release from the bFGF-incorporating microspheres was studied. Approximately 30% of incorporated bFGF was released from the acidic gelatin microsphere within the initial 3 h, followed by no substantial release, whereas the basic gelatin microsphere released almost completely the incorporated bFGF within 1 day. It is likely that when basic bFGF molecules were immobilized to the acidic gelatin constituting microspheres through polyion complexation, they were not readily released under the in vitro nondegradation condition of gelatin. Incorporation of anionic carboxylmethyl cellulose (CMC) into the acidic gelatin microspheres reduced the amount of bFGF desorbed initially. This indicates that the initial burst is ascribed to free bFGF which is not ionically interacted with the acidic gelatin. CMC will function as a bFGF sorbent to suppress the initial leakage from the microspheres. When injected subcutaneously into the mouse back, bFGF-incorporating acidic gelatin microspheres were degraded over time and induced neovascularization around the injection site, in marked contrast to bFGF in the solution form. CMC incorporation slowed down the biodegradation and vascularization effect of bFGF-incorporating gelatin microspheres. It was concluded that the gelatin microsphere was a promising carrier matrix of bFGF to enhance the vascularization effect.     

Development of biodegradable poly(propylene fumarate)/poly(lactic-co-glycolic acid) blend microspheres. II. Controlled drug release and microsphere degradation

This article describes the effects of six processing parameters on the release kinetics of a model drug Texas red dextran (TRD) from poly(propylene fumarate)/poly(lactic-co-glycolic acid) (PPF/PLGA) blend microspheres as well as the degradation of these microspheres. The microspheres were fabricated using a double emulsion-solvent extraction technique in which the following six parameters were varied: PPF/PLGA ratio, polymer viscosity, vortex speed during emulsification, amount of internal aqueous phase, use of poly(vinyl alcohol) in the internal aqueous phase, and poly(vinyl alcohol) concentration in the external aqueous phase. We have previously characterized these microspheres in terms of microsphere morphology, size distribution, and TRD entrapment efficiency. In this work, the TRD release profiles in phosphate-buffered saline were determined and all formulations showed an initial burst release in the first 2 days followed by a decreased sustained release over a 38-day period. The initial burst release varied from 5.1 (+/-1.1) to 67.7 (+/-3.4)% of the entrapped TRD, and was affected most by the viscosity of the polymer solution used for microsphere fabrication. The sustained release between day 2 and day 38 ranged from 7.9 (+/-0.8) to 27.2 (+/-3.1)% of the entrapped TRD. During 11 weeks of in vitro degradation, the mass of the microspheres remained relatively constant for the first 3 weeks after which it decreased dramatically, whereas the molecular weight of the polymers decreased immediately upon placement in phosphate-buffered saline. Increasing the PPF content in the PPF/PLGA blend resulted in slower microsphere degradation. Overall, this study provides further understanding of the effects of various processing parameters on the release kinetics from PPF/PLGA blend microspheres thus allowing modulation of drug release to achieve a wide spectrum of release profiles.     

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50 μm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。     

In vitro and in vivo evaluation of biodegradable embolic microspheres with tunable anticancer drug release

Natural polymer-derived materials have attracted increasing interest in the biomedical field. Polysaccharides have obvious advantages over other polymers employed for biomedical applications due to their exceptional biocompatibility and biodegradability. None of the spherical embolic agents used clinically is biodegradable. In the current study, microspheres prepared from chitosan and carboxymethyl cellulose (CMC) were investigated as a biodegradable embolic agent for arterial embolization applications. Aside from the enzymatic degradability of chitosan units, the cross-linking bonds in the matrix, Schiff bases, are susceptible to hydrolytic cleavage in aqueous conditions, which would overcome the possible shortage of enzymes inside the arteries. The size distribution, morphology, water retention capacity and degradability of the microspheres were found to be affected by the modification degree of CMC. An anticancer drug, doxorubicin, was successfully incorporated into these microspheres for local release and thus for killing cancerous cells. These microspheres demonstrated controllable degradation time, variable swelling and tunable drug release profiles. Co-culture with human umbilical vein endothelial cells revealed non-cytotoxic nature of these microspheres compared to monolayer control (P > 0.95). In addition, a preliminary study on the in vivo degradation of the microspheres (100–300 μm) was performed in a rabbit renal embolization model, which demonstrated that the microspheres were compatible with microcatheters for delivery, capable of occluding the arteries, and biodegradable inside arteries. These microspheres with biodegradability would be promising for embolization therapies.