载万古霉素PLGA-PEG-PLGA温度敏感水凝胶的体外抗菌性能

利用聚乙二醇（PEG 1500）引发乙交酯和D,L-丙交酯开环共聚合制备聚丙交酯乙交酯（PLGA）三嵌段共聚物（PLGA-PEG-PLGA）温敏水凝胶材料,并通过核磁共振氢谱（¹H NMR）确定产物的结构及组成.应用倒置小瓶法测量得到不同浓度下PLGA-PEG-PLGA水凝胶的溶胶-凝胶相变温度为27~32℃.此外,体外降解实验及细胞毒性实验结果表明,质量分数为25%的水凝胶有满意的降解速度及良好的生物相容性.同时,利用紫外-可见光谱分析了载万古霉素水凝胶的体外药物释放行为,结果表明,万古霉素可以持续释放12 d.抗菌实验结果表明,载万古霉素水凝胶具有良好的抗菌效果.表明PLGA-PEG-PLGA三嵌段温敏水凝胶是一种较理想的万古霉素缓释载体,具有良好的临床应用前景.     

壳聚糖载药阿司匹林复合纤维的制备及其释药性能

为研制具有缓释效果的解热镇痛材料,以阿司匹林(Asp)为模型药剂、壳聚糖(CS)为纺丝基材、聚丙烯酸钠(PAAS)为助纺高分子,采用静电纺丝和热处理制备了Asp-CS/PAAS复合纤维材料;研究了热处理温度对复合纤维微观形貌、化学结构、力学性能以及体外释药行为的影响。结果表明:以10wt%的聚丙烯酸钠作为共纺高分子可以形成直径约886 nm的纤维,热处理温度的提高可以提高纤维的耐溶剂性能,但会降低纤维的拉伸强度;进一步的研究结果表明简单的热处理可以调控纤维的溶胀性能,从而实现调节阿司匹林药物的释放速率,缓释曲线符合Higuchi模型。     

孕二烯酮生物可降解缓释植入剂的制备及体外药物释放

以聚己内酯(PCL)为载体材料,采用双螺杆挤出工艺制备了孕二烯酮缓释植入剂。采用凝胶渗透色谱仪(GPC)测定分子量,扫描电镜(SEM)观察结构,红外光谱分析(FT-IR)分析药物载体状态,紫外分光光度法(UV)测定植入剂的载药量和药物释放情况。结果表明:挤出后载体分子量无明显变化;挤出工艺对载药植入剂成形性好,表面无药物析出;药物与载体以物理混合方式存在;该植入剂在体外可长效释药,趋于一级药物释放模式(r2=0.9948)。     

海藻酸壳聚糖可塑性支架材料的制备及表征

利用海藻酸钠和壳聚糖2种原料, 采用阴阳离子静电复合原理, 通过滴注法层层自组装成可搭载药物的缓释微球, 再按一定比例与海藻酸钠-壳聚糖溶液混合制成缓释微球型支架材料, 将缓释微球结构嵌入疏松多孔海绵状结构中. 研究了缓释微球的组分比对缓释微球型支架材料的孔隙率、 收缩率、 亲水性及降解性能的影响; 扫描电子显微镜照片显示, 微球结构相对完整, 多孔海绵状结构孔径为140~200 μm; 支架浸出液细胞毒性检测实验组对照组未见差异. 缓释微球体积所占比例即组分比为10%的缓释微球型支架材料孔隙率最高为68.2%~70.8%, 亲水性最好, 收缩率最低为4.4%~5.2%; 支架降解速率随缓释微球组分比升高而减慢, 组分比为20%的缓释微球型支架材料综合性能更优; 缓释微球型支架材料冻干成型前为液态, 具有良好可塑性. 缓释微球型支架材料为缓释系统与多孔支架材料有机结合提供了新思路.     

聚磷酸酯医用材料

聚磷酸酯是一种生物相容性好、结构较易进行修饰和功能化的生物降解高分子，可以应用于药物缓释材料、组织工程材料、动物体内显影剂等医用领域。本文论述了近年来的聚磷酸酯医用材料的研究进展，尤其是作为药物缓释材料的合成与应用情况。随着合成研究的深入，聚磷酸酯在医用材料方面的应用将更加引人注目。     

庆大霉素对羟基磷灰石/壳聚糖复合材料性能的影响

羟基磷灰石/壳聚糖-庆大霉素(HA/CS-G)缓释材料为骨髓炎的定点缓释给药提供了一种有效的局部药物缓释体系。为了研究抗生素对羟基磷灰石/壳聚糖材料性能的影响,采用共沉淀法制备了HA/CS-G缓释材料。利用红外光谱(IR)、X射线衍射(XRD)和扫描电子显微镜(SEM)对材料进行了表征。以不载药的羟基磷灰石/壳聚糖(HA/CS)为对照,研究了庆大霉素对HA/CS复合材料抑菌性能、力学性能和降解性能等的影响。实验结果表明,HA/CS-G有良好的抑菌效果。负载庆大霉素后HA/CS的机械强度明显增强,而材料的降解速率有所下降。本文采用的二次成型技术显著增大了材料的机械强度。     

药用缓释辅料——羟丙基甲基纤维素的合成及其缓释性能的研究

本文研究了药物缓释材料HPMC的合成方法,探讨了碱纤维素制备,醚化剂浓度,混合醚化剂配经以及产品后处理对高粘度HPMC的影响。本文还初步对KCl,氨茶碱,硝酸异山梨醇酯等药物采用合成的HPMC作辅料,进行了缓释制剂的研究,结果表明合成的HPMC具有满意的缓释性能。     

蒿甲醚缓释片体外释放研究

目的:建立蒿甲醚缓释片体外释放的含量测定方法,并对其进行体外释放考察。方法:以释放介质作为酸消解溶剂,用酸消解间接紫外分光光度法测定片剂在释放过程中的累计百分释放度;浆法考察片剂的体外释放。结果:优选了最佳酸消解条件,并确定了片剂体外释放含量测定方法:蒿甲醚缓释片2h,5h,10h的体外累计百分释放度分别为25%,60%,85%;在诸多因素中离子强度是影响缓释片释放较灵敏的因素。结论:方法准确、快速、可行,适于体外释放实验样品量大的要求;体外实验表明蒿甲醚缓释片具有比普通片明显的缓释效果。     

新型介孔羟基磷灰石/壳聚糖-万古霉素药物释放系统复合材料的制备及体外抗菌和成骨能力

采用冷冻干燥法合成了介孔羟基磷灰石(HA)/壳聚糖(CS)-万古霉素(VCM)药物释放系统复合材料, 利用SEM, XRD和FTIR等方法对材料进行了表征. 结果证实CS与HA混合复合材料具有良好的孔径和孔隙率, 万古霉素吸附于复合材料的表面和内部. 细胞毒性实验[噻唑蓝(MTT)比色法]结果表明, 材料可以促进成骨细胞增殖且具有良好的细胞相容性. 体外抑菌实验结果证实此材料可长时间抑制耐甲氧西林金葡菌(MRSA)的生长, 具有良好的抑菌和杀菌能力. 细胞黏附实验结果表明, 成骨细胞附着于材料表面增殖并通过孔道延伸. 实时聚合酶链式反应(RT-PCR)实验结果表明, 在成骨相关标志产物胶原蛋白-1(COL-1)及骨形态发生蛋白-2(BMP-2)基因上均有较高的表达, 表明材料在体外可以促进成骨细胞生长, 具有良好的成骨能力.     

生物农药微胶囊壁材料研究

用原位聚合法对生物农药阿维菌素进行包囊,然后制备微胶囊制剂,并对用于该制剂的两种高分子囊壁材料-三聚氰胺甲醛树脂和脲醛树脂的性能进行了研究。结果表明,两种树脂皆为较好的生物农药用微胶囊缓释剂型的囊壁材料,其制备工艺简单,具有良好的稳定性、粒径大小与分布、悬浮性、缓释性等,包封率均达80％以上。其中三聚氰胺甲醛树脂悬浮性较脲醛树脂更好,缓释性更持久。     

Structural and thermal properties of spray-dried methotrexate-loaded biodegradable microparticles

Drug–polymer interactions, structural properties, thermal behavior, and stability of biodegradable microparticles are fundamental aspects in the developing of new polymeric drug delivery systems. In this study, poly (d,l-lactide-co-glycolide) (PLGA) microparticles containing methotrexate (MTX) were successfully obtained by spray drying. Scanning electronic microscopy, differential scanning calorimetry (DSC), thermogravimetry (TG), X-ray diffraction (XRD), and drug-loading efficiency were used to investigate the effect of drug–polymer ratio and its interactions, in a new MTX-loaded PLGA spray-dried microparticles. High levels of encapsulation efficiency (about 90 %) and a prevalent spherical shape were identified for different drug–polymer ratios used (9, 18, and 27 % m/m). The thermal analyses (DSC and TG) and XRD indicate that MTX is homogeneously distributed in the polymeric matrix, with a prevalent amorphous state in a stable molecular dispersion. Therefore, a correlation between drug content and the structural-thermal properties of drug-loaded PLGA microparticles was established using the thermal analysis data. The biodegradable microparticle leads to an increment of thermal stability of MTX, confirming that spray drying is an efficient process for obtaining MTX-loaded PLGA microparticles.     

The effect of formulation variables on the characteristics of insulin-loaded poly(lactic-co-glycolic acid) microspheres prepared by a single phase oil in oil solvent evaporation method

Biodegradable polymeric microspheres are ideal vehicles for controlled delivery applications of drugs, peptides and proteins. Amongst them, poly(lactic-co-glycolic acid) (PLGA) has generated enormous interest due to their favorable properties and also has been approved by FDA for drug delivery. Insulin-loaded PLGA microparticles were prepared by our developed single phase oil in oil (o/o) emulsion solvent evaporation technique. Insulin, a model protein, was successfully loaded into microparticles by changing experimental variables such as polymer molecular weight, polymer concentration, surfactant concentration and stirring speed in order to optimize process variables on drug encapsulation efficiency, release rates, size and size distribution. A 2⁴ full factorial design was employed to evaluate systematically the combined effect of variables on responses. Scanning electron microscope (SEM) confirmed spherical shapes, smooth surface morphology and microsphere structure without aggregation. FTIR and DSC results showed drug–polymer interaction. The encapsulation efficiency of insulin was mainly influenced by surfactant concentration. Moreover, polymer concentration and polymer molecular weight affected burst release of drug and size characteristics of microspheres, respectively. It was concluded that using PLGA with higher molecular weight, high surfactant and polymer concentrations led to a more appropriate encapsulation efficiency of insulin with low burst effect and desirable release pattern.     

Controlled release of doxorubicin from electrospun MWCNTs/PLGA hybrid nanofibers

In this study, multiwalled carbon nanotubes (MWCNTs) were used to encapsulate a model anticancer drug, doxorubicin (Dox). Then, the drug-loaded MWCNTs (Dox/MWCNTs) with an optimized drug encapsulation percentage were mixed with poly(lactide-co-glycolide) (PLGA) polymer solution for subsequent electrospinning to form drug-loaded composite nanofibrous mats. The structure, morphology, and mechanical properties of the formed electrospun Dox/PLGA, MWCNTs/PLGA, and Dox/MWCNTs/PLGA composite nanofibrous mats were characterized using scanning electron microscopy (SEM), Fourier transform infrared spectroscopy, and tensile testing. In vitro viability assay and SEM morphology observation of mouse fibroblast cells cultured onto the MWCNTs/PLGA fibrous scaffolds demonstrate that the developed MWCNTs/PLGA composite nanofibers are cytocompatible. The incorporation of Dox-loaded MWCNTs within the PLGA nanofibers is able to improve the mechanical durability and maintain the three-dimensional structure of the nanofibrous mats. More importantly, our results indicate that this double-container drug delivery system (both PLGA polymer and MWCNTs are drug carriers) is beneficial to avoid the burst release of the drug and able to release the antitumor drug Dox in a sustained manner for 42 days. The developed composite electrospun nanofibrous drug delivery system may be used as therapeutic scaffold materials for post-operative local chemotherapy.     

Preparation and drug delivery study of electrospun hollow PES ultrafine fibers with a multilayer wall

The focus of this work was the preparation of hollow ultrafine fibers with a multilayer wall via coaxial electrospinning technology in one step and then studied their drug delivery properties. In this paper, by choosing a suitable dilute hydrophilic polymer solution as the core solution, polyethersulfone (PES) hollow ultrafine fibers with two different layers wall (porous structure layer and dense smooth layer) were formed during coaxial electrospinning process in one step. They showed good drug delivery capacity when curcumin was used as the model drug. There were much larger delivery amounts, more stable release rate, and higher utilization rate of PES hollow ultrafine fibers with a multilayer wall to curcumin than that of PES porous ultrafine fibers. Compared with porous ultrafine fibers, hollow ultrafine fibers with two different layers wall were more suitable to be used as drug delivery materials. Besides, between the two hollow ultrafine fibers with two different layers wall mentioned in this paper, there was much better drug delivery capacity for the hollow fibers produced with the core solution of PVA/DMSO. These results showed that PES hollow ultrafine fibers with two different layers wall have the potential to be used as the drug delivery materials.     

Encapsulation and sustained release of a model drug, indomethacin, using CO(2)-based microencapsulation

A carbon dioxide (CO(2))-based microencapsulation technique was used to impregnate indomethacin, a model drug, into biodegradable polymer nanoparticles. Compressed CO(2) was emulsified into aqueous suspensions of biodegradable particles. The CO(2) plasticizes the biodegradable polymers, increasing the drug diffusion rate in the particles so that drug loading is enhanced. Four types of biodegradable polymers were investigated, including poly(d,l-lactic acid) (PLA), poly(d,l-lactic acid-co-glycolic acid) (PLGA) with two different molar ratios of LA to GA, and a poly(d,l-lactic acid-b-ethylene glycol) (PLA-PEG) block copolymer. Biodegradable nanoparticles were prepared from polymer solutions through nonsolvent-induced precipitation in the presence of surfactants. Indomethacin was incorporated into biodegradable nanoparticles with no change of the particle size and morphology. The effects of a variety of experimental variables on the drug loadings were investigated. It was found that the drug loading was the highest for PLA homopolymer and decreased in PLGA copolymers as the fraction of glycolic acid increased. Indomethacin was predicted to have higher solubility in PLA than in PLGA based on the calculated solubility parameters. The drug loading in PLA increased markedly as the temperature for impregnation was increased from 35 to 45 degrees C. Drug release from the particles is a diffusion-controlled process, and sustained release can be maintained over 10 h. A simple Fickian diffusion model was used to estimate the diffusion coefficients of indomethacin in the biodegradable polymers. The diffusion coefficients are consistent with previous studies, suggesting that the polymer properties are unchanged by supercritical fluid processing. Supercritical CO(2) is nontoxic, easily separated from the polymers, can extract residual organic solvent, and can sterilize biodegradable polymers. The CO(2)-based microencapsulation technique is promising for the production of drug delivery devices without the use of harmful solvents.     

Study of types and mixture ratio of organic solvent used to dissolve polymers for preparation of drug-containing PLGA microspheres

The effects of the types and the ratios of various organic solvents used as a mixtures to dissolve poly (lactide-co-glycolide) (PLGA) by using a solvent evaporation method, a technique used to prepare polymer particles, were carefully studied in order to investigate their advantages in developing drug delivery system (DDS) formulations for the prepared microspheres. The particle size and drug loading efficiency of drug-containing PLGA microspheres were found to be dependent on the types of solvent used due to the interfacial tension between the organic solvent and water phase. The drug loading efficiency of monodisperse microspheres prepared by using a membrane emulsification technique employing organic solvents and high interfacial tension for dissolving the PLGA was increased in a controlled manner. The organic solvents with high interfacial tension in the water phase used for the preparation of polymer particles by means of the solvent evaporation method were found to be suitable in terms of improvement in the properties of DDS formulations.     

Development of PEG-PLA/PLGA microparticles for pulmonary drug delivery prepared by a novel emulsification technique assisted with amphiphilic block copolymers

We developed a novel "spray dry-based" method for preparing surface-modified particle via "block copolymer-assisted" emulsification/evaporation for pulmonary drug delivery. The method included three steps: (1) o/w emulsion containing both hydrophobic polymers and amphiphilic block copolymers was obtained by emulsification of water and a polymer-containing organic solvent, (2) the o/w emulsion was misted with a nebulizer, and (3) the emulsion mists were dried by a heater. In this way, the hydrophobic polymers and the hydrophobic part of the amphiphilic block copolymers gradually tangled during the evaporation of organic solvents from the o/w emulsion. Consequently, the hydrophilic polymer chain was introduced on the particle surface. The particle surface can be easily modified although there are no reactive groups in the hydrophobic polymer molecules. We successfully obtained dry PEG-PLA/PLGA microparticles by controlling the weight ratio of the block copolymer and the hydrophobic polymer. The introduction of PEG to the particle surface involves an increase in the Zeta potential of the particles. Interestingly, the "dimpled" microparticles having a diameter of approximately 2 μm were obtained. The "dimpled" microparticles can serve as drug carriers for pulmonary drug delivery, because the particles have a large surface area. We expect that this novel surface-modification technique will enable efficient fabrication of particles in drug delivery systems.     

Electrohydrodynamic atomization for biodegradable polymeric particle production

Electrohydrodynamic atomization (EHDA) has many applications such as electrospray ionization in mass spectroscopy, electrospray deposition of thin films, pharmaceutical productions, and polymeric particle fabrications for drug encapsulation. In the present study, EHDA was employed to produce biodegradable polymeric micro- and nanoparticles. The effects of processing parameters such as polymer concentration, flow rate, surfactants, organic salt, and setup configurations on the size and morphology of polymeric particles were investigated systematically. By changing the various processing parameters, controllable particle shape and size can be achieved. PLGA nanoparticles with size of around 250 nm can be obtained by using organic salts to increase the conductivity of the spraying solution even at a relatively high flow rate. A higher flow rate has the advantage of producing a stable cone spray and can be easily reproduced. Solid and porous particles can be fabricated using different experimental setups to control the organic solvent evaporation rate. Also, paclitaxel, a model antineoplastic drug, was encapsulated in polymeric particles which can be employed for controlled release applications. In short, EHDA is a promising technique to fabricate polymeric micro- or nanoparticles which can be used in drug delivery systems.     

聚乳酸-乙醇酸/纳米氧化锌复合电纺纤维装载亲疏水药物的控释及体外细胞毒性

利用静电纺丝技术制备了负载亲水性药物阿霉素(DOX)以及疏水性药物喜树碱(CPT)的复合纳米纤维. 先用巯基封端的普朗尼克(F127)修饰纳米氧化锌(FZnO), 再将FZnO负载盐酸阿霉素(DOX@FZnO), 最后将DOX@FZnO与CPT一起纺入聚乳酸-乙醇酸(PLGA)纤维中. 体外药物释放结果表明, 复合纳米纤维能够减小亲水性药物的突释, 减缓药物释放速率, 延长药物释放时间. 体外细胞活性结果表明, 双载药复合纤维比单载药复合纤维具有更强的细胞毒性, 能够有效抑制癌细胞生长.     

生物可降解聚酯用作蛋白质药物控释载体

聚乳酸PLA及乳酸与羟基乙酸的共聚物PLGA,由于其良好的生物相容性以及生物降解性,可用作蛋白质类药物控释体系的载体材料,同时可延长蛋白质药物的释放.本文综述了几种生物相容性聚酯及其衍生物以及它们的形成方法:(1)在PLGA的分子链中引入亲水性的含醚键的分子如PEO、PEG,来提高聚合物的亲水性,形成PLGA嵌段共聚物;(2)将细胞可接受的片段或多肽固定在聚合物支架表面,来增强PLGA与细胞间的粘附力,得到靶向的PLGA衍生物;(3)改变PLGA载体内的酸性环境,提高蛋白质药物在载体中的稳定性,发展了支化聚酯PVA-g-PLGA,并得到均速的药物释放.以上这些方法所得到的聚酯及其衍生物,均可作为蛋白质类药物安全、可靠的载体材料.