氟尿嘧啶/左旋聚乳酸生物可降解纤维支架载药体系构建与缓释效应

目的 研发一种可供机体埋植的长效的氟尿嘧啶载药纤维支架.方法 有机相分离法制备纤维,扫描电镜（SEM）观察纤维形态,光学显微镜测定纤维直径,红外光谱分析（FTIR）和差示扫描热分析（DSC）鉴定药物载体结合状态并测定纤维中PLLA的结晶度,紫外分光光度法（UV）测定纤维的载药量以及体外释放.结果 制备出微米级的载药纤维,载药量与载药效率均较高;药物与聚乳酸属于简单物理混合;相对应两种结构模式载药纤维呈现两种释放模式.结论 b型结构纤维适合于开发成长效的在位埋植载药纤维支架.     

生物可降解载药纤维的成形特性的研究

为了开发一种用于治疗肿瘤的局部定位缓释给药系统，本研究在室温条件制备了生物可降解的聚乳酸（PLLA）纤维，并且详细研究了制备过程中的处方工艺条件（聚合物分子量、聚合物浓度、注射速度、出口口径以及固化液的种类）对聚乳酸纤维的成形特性（纤维直径、纤维的表面与内部结构以及纤维的结晶度）的影响。此外，还在聚乳酸纤维上上载了一种脂溶性模型药物（尼莫地平），并对载药纤维的体外释放性质进行了研究。结果表明，这类载药纤维可以成为一种有开发前景的局部定位给药缓释系统。     

缓释双药物载体制备与性能CSCD

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,90d体外累积释放率可达到80%和90%。90d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,59d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。     

聚乳酸载药纳米微粒的表面修饰及体外评价

本研究的目的是用O 羧甲基壳聚糖作乳化剂和表面修饰剂 ,采用超声乳化法制备聚乳酸载药纳米微粒 ,并对聚乳酸载药纳米微粒进行表面修饰 ,然后分别对载药纳米微粒的表面形貌、粒径分布、微粒结构、表面元素、体外释放和肿瘤细胞抑制率等微粒性能进行考察与评价。实验证明 ,O 羧甲基壳聚糖可用于制备纳米药物载体系统 ,对聚乳酸载药纳米微粒的制备起到很好的乳化性能和表面修饰作用。采用复乳法制备包载 5 Fu的PLA/O CMC纳米微粒的平均粒径在 5 0nm ,在PBS缓冲溶液中释放时间可达 12d。在对胃癌、乳腺癌和大肠癌三种肿瘤细胞的抑制率测定实验中 ,PLA/O CMC纳米微粒的肿瘤细胞抑制率分别可以达到 72 .8%、77.3%和 75 .6 % ,接近或等同于游离 5 Fu药物的抑制率。在作用时间上 ,PLA/O CMC载药纳米微粒也显示出良好的缓释效应。     

硫酸钙/庆大霉素、硫酸钙/聚乳酸/庆大霉素释药系统的制备与特性分析

目的构建新型骨植入型抗生素释放系统,硫酸钙／庆大霉素、硫酸钙／聚乳酸／庆大霉素释药系统,探讨抗生素释放系统的制备可行性。方法以自行研制的硫酸钙或硫酸钙与聚乳酸的复合物作为抗生素载体,构建抗生素释放系统,对其进行电镜扫描,晶体衍射分析和体外降解实验以分析其构成特点、理化特性和降解特点。结果所构建的抗生素释药系统主要成分为二水硫酸钙,具有初始的生物力学抗压缩强度,具有一定的孔隙率,硫酸钙／聚乳酸／庆大霉素中,聚乳酸对硫酸钙形成包裹。体外可降解,硫酸钙／聚乳酸／庆大霉素降解时间长于硫酸钙／庆大霉素。结论以硫酸钙和硫酸钙聚乳酸复合物作为载体构建抗生素释放系统能够满足药物释放和骨内植入的要求,具有制备的可行性。     

基于微喷技术的钛合金表面载药涂层制备方法

为了探究微喷技术在钛合金表面制备载药涂层的应用,采用数字化微喷系统在钛合金片表面制备含抗生素三氯生的聚乳酸-羟基乙酸(poly(lactic-co-glycolic acid),PLGA)涂层。通过控制主要参数变量电压和频率,探究喷射参数对喷射过程的影响,进而优化喷射参数,制备载药涂层。采用扫描电子显微镜(SEM)观测涂层表面,评价其形貌特征;将制备的载药涂层置于PBS缓冲液中进行体外模拟释放实验,分析数据并绘制药物释放曲线。结果表明,数字化微喷技术应用于载药涂层制备方面具备可行性,通过控制喷射参数,获得了表面均匀、平滑的载药涂层,并且涂层的药物释放曲线也表明,该涂层的药物释放能够达到有效抑菌浓度范围。     

壳寡糖－聚乳酸阿霉素胶团体外缓释性能考察

目的：考察阿霉素壳寡糖-聚乳酸嫁接物胶团的缓释性能。方法以超声分散法制备嫁接物胶团;以阿霉素为模型药物,透析法制备载药胶团。进行载药胶团体外释放实验,考察壳寡糖-聚乳酸共聚物胶团的缓释性能。结果在壳寡糖-聚乳酸嫁接物中,聚乳酸分子量为5000的两种壳寡糖-聚乳酸嫁接物载药胶团体外释放缓释效果明显。结论壳寡糖-聚乳酸聚合物胶团具有显著的缓释特征。其中聚乳酸分子量为5000的壳寡糖-聚乳酸嫁接物,缓释效果更明显。     

rhBMP-2/聚乳酸与聚乙醇酸共聚物载药微球的制备及成骨活性研究

目的制备一种具有良好降解性和成骨活性可注射的rhBMP-2载体材料。方法采用复乳-溶剂蒸发技术制备携载rhBMP-2的聚乳酸与聚乙醇酸共聚物P(LGA)微球。测定材料的制备参数及其特性,包括材料的形貌、载药率、释药速度,并将载药微球植入鼠股部肌袋,通过X线、组织学评价载体材料的异位成骨能力。结果载药微球粒径为(253±64)μm,载药率0.52%±0.14%,载药微球rhBMP-2体外释放24h时为15.2%±0.8%,随后呈持续缓慢释放,28d时总计达48.6%±5.3%。载药微球植入鼠股部肌袋4周,材料周围有明显的骨形成。结论载有rhBMP-2的PLGA微球具有良好的缓释效果和生物活性,是一种较为理想的生长因子载体材料和释放系统。     

载异烟肼利福平聚乳酸纳米粒的制备及体外释药**

背景：微载体药物因具有靶向性、控释性、稳定性、更好的安全性备受关注。 目的：观察载异烟肼利福平两种抗结核药于同一聚乳酸纳米粒的给药系统及体外释放特性。 方法：采用改良的自乳化二元溶剂扩散法制备载异烟肼和利福平纳米粒,亚微粒径分析仪测定纳米粒粒径及分布,透射电镜观察其形态;高效液相色谱仪建立测定异烟肼、利福平的载药量和包封率;以磷酸盐缓冲液为释放介质,观察载异烟肼和利福平纳米粒的体外释药特性。 结果与结论：载利福平和异烟肼纳米粒表面完整光滑,无明显粘连现象,纳米粒均匀度好。亚微粒径分析仪测定纳米粒平均粒径80.4 nm。异烟肼载药量为(15.95±1.34)%,包封率为(5.01±0.17)%;利福平载药量为(4.66±0.97)%,包封率为(4.05±0.18)%。体外释药结果显示纳米粒的体外释药过程较平稳。突释期纳米粒中异烟肼释放度为15.22%,到3 d累积释放度可达95.6%;利福平释放度为9.26%,到3 d累积释放度可达90.3%。提示采用改良的自乳化二元溶剂扩散法制备载异烟肼和利福平纳米粒,所得载药纳米粒的粒径小且较均匀。纳米粒体外释药过程较平稳,无明显突释现象。关键词：聚乳酸;异烟肼;利福平;纳米粒;体外释药 doi:10.3969/j.issn.1673-8225.2012.16.014     

体外研究聚合物P(DLLA-co-TMC)的降解性能与释药行为

目的 研究P(DLLA-co-TMC)聚合物的体外降解性能与释药行为,且探讨该聚合物作为长效避孕释放载体的可行性.方法 以PBS溶液为溶媒研究P(DLLA-co-TMC)的降解性能;以P(DLLA-co-TMC)聚合物为载体制备含孕二烯酮的载药片,并通过蒸馏水浸泡载药片研究载药体系的体外释药行为.结果 P(DLLA-co-TMC)聚合物前期降解较慢,第30天和第90天失重率分别为10.0%和12.3%,后期降解速率较快,第120天的失重率为59.3%;P(DLLA-co-TMC)的载药片前期释药速率较大,出现"暴释现象",后期释药速率减缓并逐渐趋于平稳,第100天时累计释放率为5.64%.结论 P(DLLA-co-TMC)聚合物降解性能良好、释药效果明显,有望通过体内研究使含孕二烯酮的P(DLLA-co-TMC)聚合物载药系统应用于长效埋植避孕.     

Fabrication of drug-loaded electrospun aligned fibrous threads for suture applications

In this work, drug-loaded fibers and threads were successfully fabricated by combining electrospinning with aligned fibers collection. Two different electrospinning processes, that is, blend and coaxial electrospinning, to incorporate a model drug tetracycline hydrochloride (TCH) into poly(L-lactic acid) (PLLA) fibers have been used and compared with each other. The resulting composite ultrafine fibers and threads were characterized through scanning electron microscopy, transmission electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction, differential scanning calorimetry, and tensile testing. It has been shown that average diameters of the fibers made from the same polymer concentration depended on the processing method. The blend TCH/PLLA fibers showed the smallest fiber diameter, whereas neat PLLA fibers and core-shell TCH-PLLA fibers showed a larger proximal average diameter. Higher rotating speed of a wheel collector is helpful for obtaining better-aligned fibers. Both the polymer and the drug in the electrospun fibers have poor crystalline property. In vitro release study indicated that threads made from the core-shell fibers could suppress the initial burst release and provide a sustained drug release useful for the release of growth factor or other therapeutic drugs. On the other hand, the threads from the blend fibers produced a large initial burst release that may be used to prevent bacteria infection. A combination of these results suggests that electrospinning technique provides a novel way to fabricate medical agents-loaded fibrous threads for tissue suturing and tissue regeneration applications.     

Functionalization of electrospun poly(caprolactone) fibers for pH-controlled delivery of doxorubicin hydrochloride

Functionalized electrospun polymer fibers are a promising candidate for controlled delivery of chemotherapeutic drugs to improve the therapeutic efficacy and to reduce the potential toxic effects by delivering the drug at a rate governed by the physiological need of the site of action. In this study, poly(caprolactone) (PCL) fibers were fabricated by electrospinning, followed by hydrolyzation to introduce functional groups on the fiber surface. Characterization studies were performed on these functionalized fibers using X-ray photoelectron spectroscopy, scanning electron microscopy, and Toluidine Blue O dye assay. The pH-sensitivity of the functional groups on the fiber surface and doxorubicin hydrochloride was utilized to bind the drug electrostatically to these functionalized PCL fibers. The effect of pH on drug loading and release kinetics was investigated. Results indicate successful electrostatic binding of the drug to functionalized electrospun fibers and a high drug payload. The drug delivery response can be modulated by introduction of suitable stimuli (pH).     

Encapsulating drugs in biodegradable ultrafine fibers through co-axial electrospinning

This article describes an electrospinning process to fabricate double-layered ultrafine fibers. A bioabsorbable polymer, Polycaprolactone (PCL), was used as the outer layer or the shell and two medically pure drugs, Resveratrol (RT, a kind of antioxidant) and Gentamycin Sulfate (GS, an antibiotic), were used as the inner layers or the cores. Morphology and microstructure of the ultrafine fibers were characterized by scanning electron microscope (SEM) and transmission electron microscopy (TEM), whereas mechanical performance of them was understood through tensile test. In vitro degradation rates of the nanofibrous membranes were determined by measuring their weight loss when immersed in pH 7.4 phosphate-buffered saline (PBS) mixed with certain amount of Pseudomonas lipase for a maximum of 7 days. The drug release behaviors of the RT and GS were measured using a high performance liquid chromatography (HPLC) and ultraviolet-visible (UV-vis) spectroscopy, respectively. It has been found that the drug solutions without any fiber-forming additive could be encapsulated in the PCL ultrafine fibers, although they alone cannot be made into a fiber form. Beads on the fiber surface influenced the tensile behavior of the ultrafine fibers remarkably. When the core solvent was miscible with the shell solvent, higher drug concentration decreased the bead formation and thus favored the mechanical performance. The situation, however, became different if the two solvents were immiscible with each other. The degradation rate was closely related to hydrophilicity of the drugs in the cores. Higher hydrophilicity apparently led to faster degradation. The release profiles of the RT and GS exhibited a sustained release characteristic, with no burst release phenomenon.     

Biodegradable microparticles and fiber fabrics for sustained delivery of cisplatin to treat C6 glioma in vitro

The duration of cisplatin release from most of the drug delivery devices seemed to be shorter than 14 days except large microparticles. The objective of this study was to fabricate and characterize cisplatin-loaded PLA microparticles, PLA/PLGA (30/70) composite microparticles, and fibers as formulations for long-term sustained delivery of cisplatin to treat C6 glioma in vitro by electrospray and electrospinning techniques. Cisplatin-loaded biodegradable microparticles with particle size of around 5 microm and fiber fabrics with diameter of 0.5-1.7 microm were obtained using electrospray and electrospinning techniques. Encapsulation efficiency and in vitro release of formulations were measured by ICP-OES. The encapsulation efficiency for different samples of microparticles was approximately from 33% to 72% and the fiber fabrics had encapsulation efficiency greater than 90%. Cisplatin-loaded microparticles showed typical characteristics of cisplatin release profile: a large initial burst followed by a sustained slow release of 35 days. The composite PLA/PLGA (30/70) microparticles could reduce the initial burst release of cisplatin because of their core-shell structures. In contrast, more than 75 days sustained release could be achieved by fiber fabric formulations without large initial burst. MTT assay was used to quantify the cytotoxicity of different formulations against C6 glioma cells. Microparticle formulations had slightly higher cytotoxicity than free drug. In contrast, the cytotoxicity of fiber fabrics formulation was around 4 times higher than of the free drug based on the actual amount of drug released. The microparticle and fiber fabric formulations presented may be promising for the sustained delivery of cisplatin to eliminate the undesired side effects caused by direct injection of cisplatin solution in systemic administration.     

Drug release characteristics of phase separation pHEMA sponge materials

A number of phase separation pHEMA sponge hydrogels have been prepared based on variations in monomer contents, concentration of cross-linking agent, solvent mixture and temperature of polymerization. The loading levels and release profiles of the anti-inflammatory drug prednisolone were examined for each of the pHEMA sponge materials. An effective diffusion coefficient determined by an optimization approach based on the experimental data was used to measure their release characteristics. The effect of morphological variations, revealed by the environmental scanning electron microscopy, and polymer/solvent volume fractions on these properties were discussed.     

Hydrogel swelling as a trigger to release biodegradable polymer microneedles in skin

Biodegradable polymeric microneedles were developed as a method for achieving sustained transdermal drug release. These microneedles have potential as a patient-friendly substitute for conventional sustained release methods. However, they have limitations related to the difficulty of achieving separation of the needles into the skin. We demonstrated that microneedle separation into the skin was mediated by hydrogel swelling in response to contact with body fluid after the needles were inserted into the skin. The hydrogel microparticles were synthesized by an emulsification method using poly-N-isopropylacrylamide (PNIPAAm). The microneedles were fabricated by micromolding poly-lactic-co-glycolic acid (PLGA) after filling the cavities of the mold with the hydrogel microparticles. The failure of microneedle tips caused by hydrogel swelling was studied in regard to contact with water, insertion of microneedles into porcine cadaver skin in vitro, stress-strain behavior, and insertion into the back skin of a hairless mouse in vivo. The drug delivery property of the hydrogel particles was investigated qualitatively by inserting polymer microneedles into porcine cadaver skin in vitro, and the sustained release property of PLGA microneedles containing hydrogel microparticles was studied quantitatively using the Franz cell model. The hydrogel particles absorbed water quickly, resulting in the cracking of the microneedles due to the difference in volume expansion between the needle matrix polymer and the hydrogel particles. The swollen particles caused the microneedles to totally breakdown, leaving the microneedle tips in the porcine cadaver skin in vitro and in the hairless mouse skin in vivo. Model drugs encapsulated in biodegradable polymer microneedles and hydrogel microparticles were successfully delivered by releasing microneedles into the skin.     

药物缓释载体材料在医药领域中的研究及应用

背景：药物缓释就是将小分子药物与高分子载体以物理或化学方法结合,在体内通过扩散、渗透等控制方式,将小分子药物以适当的浓度持续地释放出来,从而达到充分发挥药物功效的目的。 目的：总结药物缓释载体材料特征及其在医药领域中的应用。 方法：以“药物缓释、载体材料、生物降解、壳聚糖、聚乳酸、海藻酸钠”为中文关键词,以“Drug delivery,carrier material,biodegradable,chitosan,polylactic acid, sodium alginate”为英文关键词,采用计算机检索中国期刊全文数据库、PubMed数据库(1993-01/2010-11)相关文章。纳入高分子生物材料-药物缓释载体等相关的文章,排除重复研究或Meta分析类文章,共入选31篇文章进入结果分析。 结果与结论：壳聚糖和聚乳酸是当前在药物缓释体系中应用较多的材料,它是将小分子药物与高分子载体以物理或化学方法结合, 以适当的浓度持续地释放出来,从而达到充分发挥药物功效的目的,较单一生物材料具有显著优越性,具有更好的生物相容性和生物可降解性。目前很多研究仍处于实验阶段,还有一些问题有待于解决,如制剂质量方法不成熟,剂量较难控制,成本较高等。