5-氟尿嘧啶载药微球的制备工艺及性能研究

以PLA为载体材料,以5-Fu为模型药物,制备5-Fu/PLA载药微球,通过正交设计优化微球制备工艺.另外,检测了载药微球的回收率、稳定性、缓释性能等物理性质.用紫外分光光度计测定药物含量,激光粒度仪分析粒径. 结果表明,载药微球的平均粒径为(133.2±32.5)nm,平均包封率为(11.3±5.0)%,缓释时间延长至80～100h,具有良好的缓释功能.     

聚乳酸的直接合成及其红霉素肺靶向药物微球的应用

以DL-乳酸为原料，通过熔融聚合法直接合成外消旋聚乳酸(PDLLA)。以SnCl2为催化剂，用量O．5％(质量)，在170℃、70Pa下反应10h，获得了粘均分子量为4100的PDLLA，将其应用于红霉素肺靶向微球的载体。用正交试验确定了红霉素-聚乳酸微球(ERY—PDLLA—MS)最佳成型工艺条件，用DSC和SEM表征其成球性能。微球体外缓释半衰期为28h，175h后累积释药百分率约为80％．注射微球混悬剂的兔肺组织中药物含量为普通市售红霉素注射剂的6倍，达到了肺靶向的目的。     

高压静电抗溶剂法制备甲氨蝶呤-聚乳酸复合微球的研究

基于超临界CO2技术制备的甲氨蝶呤纳米粒为小分子模型药物,采用高压静电抗溶剂法制备甲氨蝶呤-聚乳酸复合微球。用扫描电镜(SEM)、傅立叶红外光谱仪(FT-IR)对该载药复合微球进行表征,并研究其载药量、包封率和药物释放曲线。实验结果表明,甲氨蝶呤-聚乳酸复合微球表面光滑,粒径分布范围在10～50μm之间;FT-IR表明,在高压静电抗溶剂过程中聚乳酸化学结构无变化,有利于其作为药物载体;随着理论载药量增加(2.5%、5%和10%),包封率减少(18.0%、7.1%和2.3%);甲氨蝶呤从聚乳酸微球中释放具有长效缓释的性能,无突释效应。     

超临界流体技术制备5-氟尿嘧啶-吲哚美辛-聚乳酸缓释微球

为了考察药物5-氟尿嘧啶(5-Fu)与吲哚美辛(IDMC)的协同作用, 采用超临界流体强制分散溶液技术(SEDS), 以二氯甲烷/二甲亚砜为共溶剂, 制备了复合5-Fu和IDMC的L-聚乳酸(PLLA)微球。利用单因素法探索了制备复合微球的最佳外部条件, 通过表面形貌、 载药量、 粒径分布、 释放性能的检测和体外细胞实验来表征微球的各项性能。结果表明: 当共溶剂二氯甲烷/二甲亚砜比例为30∶1时, 制备该微球的优化条件为39℃、 14MPa; 微球形貌呈类球形, 粒径分布在0.5~5μm; 复合IDMC后微球具有更优良的缓释效果; 载药微球对A549细胞系增殖有明显的抑制作用, 但与复合IDMC前后微球共培养的2组细胞的相对生长速率(RGR)无显著性差异。      

聚乳酸头孢唑啉钠微球的制备及其性能表征

采用复乳法制备聚乳酸．头孢唑啉钠（PLA-CEZ）微球．扫描电子显微镜（SEM）和差热分析（DTA）结果表明，PLA-CEZ呈现完整的球形且聚乳酸和模型药物能够有机地结合为一体．同时，探讨了聚乳酸分子量大小及释药介质对载药微球释放速度的影响；释药曲线显示，PLA-CEZ微球具有很好的缓释效果．     

聚乳酸多孔微球的制备及释药性能

将聚乳酸(PLLA)/四氢呋喃(THF)溶液分散在甘油(连续相)中,通过自乳化结合热致相分离(TIPS)制备一系列PLLA多孔微球,微球由捆束状纳米纤维组成。通过改变PLLA浓度、(PLLA/THF)∶甘油比值、溶剂种类以及淬火温度等条件研究所得多孔微球结构与形貌。结果表明,PLLA的质量分数为2%~5%、m(PLLA/THF)∶m(甘油)=1∶3、-20℃和-196℃淬火均能得到形状规整的PLLA多孔微球。多孔微球孔隙率和比表面积最高可达95.44%和32.53m2/g。PLLA多孔微球对牛血清蛋白的药载量为0.355 mg/mg,30 h内释放率达到59.8%,是一种非常良好的药物缓释载体。     

聚乳酸微球制备工艺的研究

采用O/W乳化-溶剂挥发法,选择聚氧乙烯山梨醇酐单硬脂酸酯(Tween60)为乳化剂,天然高分子明胶作为共表面活性剂,制备出了形态较好的聚乳酸微球,而且在可确定因素固定下来后,在保证成球质量的基础上,可以分别通过调节Tween60和明胶的用量在一定范围内来控制微球的平均粒径。     

可生物降解聚乳酸载青风藤总碱微球的制备工艺

探索青风藤总生物碱微球(CSA-MS)的制备方法并优化制备工艺.采用乳化-溶剂挥发法制备CSA-MS,紫外分光光度法测定MS的包封率和栽药量,扫描电镜观察MS的形貌,粒径测定仪测MS粒径分布情况,并测试药物的体外释放情况.结果显示,MS外观圆整,平均粒径为(21.5±1.22)μm.正交实验优化了MS的制备工艺,其优化...     

壳聚糖靶向缓释功能高分子载药微球及其特性研究

采用壳聚糖作为载体,通过分子结构设计,以叶酸靶向受体改性壳聚糖,然后选择5-氟尿嘧啶为模型药物,采用复凝聚法制备新型壳聚糖靶向缓释功能高分子载药微球。通过红外光谱和1 H-NMR核磁共振分析确定了叶酸改性壳聚糖化学结构,并通过扫描电镜、激光粒度分析仪、激光共聚焦显微镜及紫外光谱等现代仪器和分析方法对载药微球的形貌结构、粒径、包埋率、载药量和体外药物释放特性等进行研究。结果表明,模型药物被成功包埋到叶酸改性后的壳聚糖微球中,包埋率E和载药量L最高可达86.5%和32.7%,载药微球的平均粒径为5.251μm,多分散系数(PDI)为0.056,球形度、分散性良好;激光共聚焦显微镜结果显示微球为核壳结构;体外释放实验表明壳聚糖靶向缓释功能高分子载药微球具有持久的缓释作用,24h后载药微球在模拟胃液(pH值=1.2)中释放率为70%,在模拟肠液(pH值=7.4)中释放率为40%,释药速度与释放介质的pH值密切相关。     

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%。     

The release of 5-fluorouracil from microspheres of poly(epsilon-caprolactone-co-ethylene oxide)

The purpose of this study was to evaluate the in vitro release of 5-fluorouracil from microspheres prepared using a novel triblock copolymer of ε-caprolactone and ethylene oxide as the encapsulating material. Microspheres of poly(ε-caprolactone-co-ethylene oxide) were prepared by employing the “hot-melt” method of microencapsulation. Microspheres were sized using sieve analysis and scanning electron microscopy (SEM). Release studies were performed using a custom-made rotating paddle dissolution apparatus. Copolymer microspheres, fabricated by the hot melt method were shown by electron microscopy to have smooth, nonporous surfaces. Drug-loaded microspheres were found to have a broad distribution of sizes, which was thought to be a consequence of the wide range of crystal sizes of the encapsulated unmilled drug. Nonlinear release kinetics were observed from microspheres in the size fraction 75-250 μm, with a pronounced “burst release” associated with the presence of drug at the surface of the microspheres. A specific delineation of the drug release mechanism was not possible due to rapid gelation, swelling, and subsequent dissolution of the microspheres that occurred on hydration. This work describes the preparation of microspheres that swell rapidly and coalesce together on hydration, accompanied by rapid drug release and copolymer dissolution over a 2-hr period.     

Enhanced anti-cancer effect of 5-fluorouracil loaded into thermo-responsive conjugated linoleic acid-incorporated poloxamer hydrogel on metastatic colon cancer models

Conjugated linoleic acid-coupled Pluronic F127 (Plu-CLA) is an effective drug delivery system with numerous advantages and anti-cancer activity. 5-FU administered in Plu-CLA hydrogel (P-FU) led to the significant enhancement of tumor growth suppression and cellular apoptosis. Moreover, growth of hepatic and intraperitoneal metastases in vivo was significantly reduced in mice treated with P-FU. Therefore, Plu-CLA could be a potential intraperitoneal carrier for hydrophilic 5-FU for the effective treatment of metastatic colon cancer.     

超临界流体技术制备吗啡/聚乳酸-聚乙二醇共聚物缓释微球

以L-聚乳酸-聚乙二醇三嵌段共聚物(PLLA-PEG-PLLA)为载体材料,通过超临界流体强制溶液分散技术制备吗啡/聚乳酸-聚乙二醇共聚物(MF/PLLA-PEG-PLLA)的复合微球,考察了PEG分子量的变化对微球性能的影响。通过表面形貌,粒径及粒径分布,载药量,包封率及释放性能来表征复合微球的各项性能;利用气相色谱法测定二氯甲烷和甲醇的残留量;通过溶血实验来评价复合微球的血液相容性。实验表明,所制备的复合微球呈球形或类球形形貌,平均粒径在1.99～6.20μm之间,载药量达到17.92%,包封率最高可至69.57%,复合微球的药物释放呈先突释后缓释的释药模式;二氯甲烷和甲醇的残留量分别为0.0076%和0.0016%;微球溶血率<1%,远小于国家标准5%,证明复合微球具有较好的血液相容性。     

壳聚糖-固态分散体载药微球的制备及性能研究

首先采用不同分子量的壳聚糖通过乳化-化学交联法制备了4种不同的壳聚糖载药微球。通过对微球的粒径、溶胀率、载药率、包封率等指标检测以及缓释性能的研究,发现分子量为240kDa的壳聚糖制备的载药微球缓释效果明显,载药率、包封率均较高,综合性能优于其它分子量壳聚糖制备的微球。利用该分子量壳聚糖包埋固态分散体制备了壳聚糖-固态分散体载药微球,改善了药物的溶解性并具有药物缓释作用。因此,壳聚糖-固态分散体载药微球是一种理想的药物缓释体系,可以用于包埋溶解性差,生物半衰期短,对胃肠刺激性强的药物。     

Synthesis of tritium-labeled 5-fluorouracil and 5-fluorocytosine

The effect of various catalysts and temperature on the solid-phase isotope exchange of 5-fluorouracil and 5-fluorocytosine with tritium was studied. The isotope exchange yielding the desired compounds is accompanied by dehalogenation and hydrogenation of the 5,6-double bond of the pyrimidine ring. Performing the reaction at a temperature below 160°C allowed the process to be carried out selectively, i.e., with the preservation of the functional groups and double bond in the starting compound. The yields of various products formed in the reactions of tritium with the above compounds were estimated. Synthesis conditions were found, and tritium-labeled 5-fluorouracil and 5-fluorocytosine were prepared with the molar radioactivity of 0.45 Ci mmol⁻¹ (16.7 TBq mol⁻¹) and 4.4 Ci mmol⁻¹ (0.16 PBq mol⁻¹), respectively, and with the purity exceeding 98%.     

Magnetically responsive,sorafenib loaded alginate microspheres for hepatocellular carcinoma treatment

This study aimed to develop sorafenib loaded magnetic microspheres for the treatment of hepatocellular carcinoma. To achieve this goal, superparamagnetic iron oxide nanoparticles (SPIONs) were synthesised and encapsulated in alginate microspheres together with an antineoplastic agent, sorafenib. In the study, firstly SPIONs were synthesised and characterised by dynamic light scattering, energy‐dispersive X‐ray spectroscopy, and scanning electron microscopy. Then, alginate‐SPIONs microspheres were developed, and further characterised by electron spin resonance spectrometer and vibrating sample magnetometer. Besides the magnetic properties of SPIONs, alginate microspheres with SPIONs were also found to have magnetic properties. The potential use of microspheres in hyperthermia treatment was then investigated and an increase of about 4°C in the environment was found out. Drug release studies and cytotoxicity tests were performed after sorafenib was encapsulated into the magnetic microspheres. According to release studies, sorafenib has been released from microspheres for 8 h. Cytotoxicity tests showed that alginate‐SPION‐sorafenib microspheres were highly effective against cancerous cells and promising for cancer therapy.Inspec keywords: drug delivery systems, drugs, nanofabrication, magnetic particles, iron compounds, scanning electron microscopy, hyperthermia, biomedical materials, encapsulation, nanoparticles, light scattering, nanomagnetics, cellular biophysics, toxicology, cancer, nanomedicine, superparamagnetism, nanocomposites, magnetometry, paramagnetic resonance, X‐ray chemical analysisOther keywords: sorafenib loaded alginate microspheres, hepatocellular carcinoma treatment, sorafenib loaded magnetic microspheres, superparamagnetic iron oxide nanoparticles, dynamic light scattering, energy‐dispersive X‐ray spectroscopy, scanning electron microscopy, electron spin resonance spectrometer, vibrating sample magnetometer, hyperthermia treatment, drug release, alginate‐SPION‐sorafenib microspheres, antineoplastic agent, cytotoxicity tests, cancerous cells, time 8.0 hour, Fe₃ O₄      

可降解聚碳酸亚丙酯马来酸酯载药微球的制备

采用阴离子配位聚合方法,合成了二氧化碳(CO2),环氧丙烷(PO)与马来酸酐(MA)的三元共聚物,聚碳酸亚丙酯马来酸酯 (PPCMA).采用复相乳液(W/O/W)溶剂挥发法制备了包裹水溶性模型药物葡萄糖(glucose)的可降解微球,并研究了壁材与囊心的比例、稳定剂明胶浓度、搅拌速率等因素对微球性能的影响.当v(PPCMA)∶v(glucose)=1∶2,gelatin质量分数为0.2%,第1次乳化搅拌速率为400r/min,第2次乳化搅拌速率为500r/min时,得到粒径较小、载药量和包封率分别为26.1%和76.1%的载药微球.     

聚乳酸纤维的物理老化性能研究

以聚乳酸(PLA)切片为原料,通过熔融纺丝和气流牵伸制备了PLA纤维,研究了PLA纤维在物理老化过程中热学性能和力学性能的变化。利用差示扫描量热仪(DSC)和电子万能强力仪分别研究了它们在物理老化过程中的玻璃化转变行为和力学性能变化。结果表明:随着物理老化时间的增加,PLA纤维的DSC升温图谱中出现了2个玻璃化转变区,且玻璃化转变温度逐渐升高;而PLA纤维的强力先增大,老化一定时间后,因PLA分子发生降解强力逐渐减小。