紫杉醇聚己内酯／泊洛沙姆188共混载药微球及其抗肿瘤活性

目的本研究首次尝试利用聚己内酯（PCL）与亲水性添加剂泊洛沙姆188（Pluronic F68,F68）共混物作为载体材料与抗癌药物紫杉醇组成微球缓释载药系统。方法采用乳化,溶剂挥发法制备紫杉醇PCL/F68共混微球;考察紫杉醇PCL／F68共混微球的表面形态、平均粒径、包埋率及体外释放性能：利用DSC法分析紫杉醇在PCL／F68共混徽球中的分散状态;考察紫杉醇PCL/F68共混微球在小鼠肝癌H22腹水瘤模型中的抗肿瘤活性。结果表明载体材料中的亲水性添加剂F68可在微球表面形成孔状结构,F68的加入提高了紫杉醇从PCL／F68共混载药微球的释放并获得了接近恒定的释放性能;在小鼠肝癌H22腹水瘤模型中。紫杉醇PCL／F68共混载药微球对肿瘤生长具有抑制作用,荷瘤小鼠生存期明显延长。结论以PCL/F68共混物为载体制备的紫杉醇控释微球具有较高的释放能力和明显的控释效果．     

生物可降解材料聚己内酯微球的细胞相容性体外研究

将聚己内酯制成平均粒径 5 .0 8± 0 .2 3μm的微球 ,采用流式细胞术研究经不同纯化处理的微球其浸提液对小鼠成纤维细胞凋亡及细胞周期的影响。结果表明 ,不同的纯化条件对聚己内酯微球的细胞相容性影响巨大。经充分洗涤干燥的产品在给药剂量范围内细胞相容性良好     

医用聚己内酯埋植剂体内降解的研究

目的 对医用聚己内酯埋植剂材料合成及体内降解进行研究,了解埋植剂材料的性能. 方法 Pluronic F68经乙酰封端处理后与己内酯单体（CL）混合,加入催化剂于N2保护的聚合釜中,在140 ℃～170 ℃条件下聚合48 h,用挤出机制成管材.研究致孔剂的工艺、微孔的形成.用核磁共振和扫描电镜等方法观察聚己内酯埋植剂材料的结构.用氚标记的低相对分子量的聚己内酯胶囊植入大鼠皮下,测定其体内降解、吸收和排泄. 结果 含有F68的医用聚己内酯埋植剂材料（PCL/F68）在亲水介质中F68很快溶出,可形成多微孔结构.该材料起始相对分子量为66 000时,在体内可完整存在2年,2年后降解为低相对分子量碎片,可被机体吸收、排泄,不在体内积蓄. 结论 聚己内酯/F68埋植剂材料在体内可降解并主要通过粪便排出体外,不在体内积蓄,脏器中放射性极少.     

聚己内酯埋植剂的制备及药物通透性研究

目的制备聚己内酯（PCL）长效药物缓释制剂,优化药物缓释效果,并研究PCL埋植剂的药物通透性.方法 合成分子质量为（8～16）×104 u含有普朗尼克F68的PCL,用挤出法制备不同壁厚的PCL长效缓释埋植剂.将左炔诺孕酮（LNG）装入PCL管封装,制成LNG药囊.通过高效液相色谱法测定LNG的释放效果,考察PCL的分子质量及PCL管壁厚度对LNG通透性的影响.结果 当PCL分子质量为（8～16）×104u时,对LNG通透性无显著影响.PCL管壁厚在0.20～0.40 mm时,对LNG通透性亦无显著影响;当壁厚小于0.15 mm时,LNG通透性显著提高.结论 PCL埋植剂对LNG具有通透性,可通过改变PCL管壁厚度增加药物通透性.     

聚己内酯/明胶复合纳米材料的细胞相容性

目的:观察真皮成纤维细胞在聚己内酯/明胶(PCL/Gel)复合纳米材料上生长与增殖情况,评价此材料的生物相容性.方法:采用静电纺丝法制备PCL/Gel复合纳米纤维,将原代培养的真皮成纤维细胞接种到材料的表面,扫描电镜观察真皮成纤维细胞在复合纳米材料上的生长情况.实验分两组,材料组和对照组分别在接种后48、72、96 h用MTT法检测细胞的增殖情况.结果:真皮成纤维细胞在PCL/Gel复合纳米材料表面贴附牢固,生长形态良好.MTT检测结果统计显示此材料能够促进真皮成纤维细胞在其表面增殖.结论:PCL/Gel复合纳米材料具有较好的生物相容性,有望作为修复足底软组织创伤的支架材料.     

聚己内酯材料的生物相容性与毒理学研究

由本实验室自行制备的,用钛酸丁酯引发的生物可降解材料聚ε-己内酯PCL,经细胞毒性试验,全身急性毒性试验,皮内刺激试验及植入试验研究,结果表明:样品中微量有机溶剂的存在对细胞毒性有一定影响.样品植入初期有轻度炎症反应,三个月后炎症反应基本消失.结论为用钛酸丁酯引发的PCL材料具有良好的生物相容性.     

新型聚己内酯/磷酸钙支架的制备及生物相容性研究

探讨新型聚己内酯(PCL)/磷酸钙(CPC)复合材料支架的制备方法及对骨髓基质细胞(BMSCs)的生物相容性。采用溶液共混法,利用可溶盐晶体做造孔剂,制备PCL/CPC复合材料支架,以单纯PCL和CPC支架为对照组,Q800型动态力学分析仪进行动态力学性能试验(DMA),采用排水法测量孔隙率;灭菌后通过与犬BMSCs体外共同培养后细胞形态、生长曲线、碱性磷酸酶(ALP)染色和半定量及骨钙素(OC)半定量等方法检测细胞在支架材料上的黏附、增殖及成骨分化情况,动物体内异位成骨检测其成骨情况。结果显示,复合材料的储能模量在PCL/CPC比例为7:3时达到最大,制得的材料孔径为250～350μm,多孔支架的孔隙率为70%～80%;BMSCs在新型PCL/CPC组、CPC组支架表面分布均匀,生长增殖明显较PCL组活跃(P<0.05);PCL/CPC组、CPC组BMSCs成骨行为与PCL组之间有显著差异(P<0.05)。动物体内异位成骨检测提示,4周时PCL/CPC组为13.78%±1.60%、CPC组BMSCs为15.29%±1.20%,成骨显著强于PCL组BMSCs的7.56%±2.20%(P<0.05),表明PCL和CPC的复合明显改善了两种材料的缺陷,获得的PCL/CPC支架具有良好的生物相容性,可与BMSCs共同构建具有成骨能力的三维立体组织工程化骨。     

新型两亲性超枝状大分子聚己内酯／聚缩水甘油醚纳米粒子实验研究

目的选择合适实验条件将两亲性超枝状大分子聚己内酯／聚缩水甘油醚制备成纳米粒子,以进一步应用于靶向药物传递载体。方法称取聚己内酯／聚缩水甘油醚（通过H^1NMR和GPC定性）30mg,溶于3mL丙酮和2mL乙醇混合溶剂中,在搅拌速度为250r／min的条件下。将上述溶液按250uL·min^-1速度注入30mL的蒸馏水中,搅拌过夜,减压挥发除掉溶剂,冷冻干燥得到纳米粒子。结果通过透射电镜观察,所得纳米粒子为球形,形状均匀,粒径约在50—100nm之间。结论本研究通过实验,首先合成分子量2×10^4U左右的聚己内酯／聚缩水甘油醚聚合物,通过×选择合适的溶剂。得到聚己内酯／聚缩水甘油醚纳米粒子。该方法操作简易,环境友好,易于后处理,所得纳米粒子大小均匀,通过后修饰,这种纳米粒子将有望被应用于体内靶向传递。     

甲壳素短纤维增强聚己内酯复合材料体外降解实验研究

将纯聚己内酯（PCL）、甲壳素短纤维增强PCL复合材料和聚DL-乳酸分别置于生理盐水溶液中,进行体外降解实验研究。于2、4、8、12、16、24周分别取材,测试降解液pH值、试样失重率及力学性能的变化,并行扫描电镜观察。结果显示甲壳素短纤维增强PCL初始强度大于纯PCL,在降解过程中,浸泡液pH值呈弱酸性和中性,失重速率快于纯PCL,力学性能先高后低,强度和模量值24周与初始值相差不大。通过以上体外降解实验可以得出结论：PCL树脂复合甲壳素纤维后,加快降解速度,提高力学性能,缓冲材料局部pH值的下降,是一种很有前途的胸壁缺损修补及骨科内固定材料。     

可生物降解材料聚己内酯在医学上的应用进展

聚己内酯是一种被FDA批准的可生物降解的聚酯材料。由于其具有在组织中可降解的能力，因此成为组织工程中可能被广泛应用的一种新材料。对聚己内酯的一些重要特性和当前在生物医学方面的应用进行综述，并指出在应用中存在的问题以及今后的研究方向。     

Fabrication of microspheres using blends of poly(ethylene adipate) and poly(ethylene adipate) / poly(hydroxybutyrate-hydroxyvalerate) with poly(caprolactone): Incorporation and release of bovine serum albumin

Spherical microspheres composed of polymer blends 80: 20 PEAD/PCL II and 40:40: 20 PEAD/P(HB-HV)/PCL II containing a range of BSA loadings have been fabricated using a single emulsion technique with solvent evaporation. 80: 20 PEAD/PCL II microspheres had smooth surfaces while 40:40:20 PEAD/P(HB-HV)/PCL II microspheres consisted of a mixture of smooth surfaced, microporous and macroporous microsphere fractions. Irrespective of fabrication polymer, microspheres were produced in high yield (> 75%) and BSA incorporation had no significant effect on microsphere size distribution which ranged from 0.6 to 5 μm and from 2.1 to 50 μm for 80: 20 PEAD/PCL II and 40:40: 20 PEAD/P(HB-HV)/PCL II microspheres, respectively. The loss of BSA by partitioning into the aqueous phase resulted in low encapsulation efficiencies (< 14.5%). BSA release increased significantly with theoretical percentage loading but the relationship could not be confirmed when the total cumulative release of BSA was expressed as a percentage of the actual total BSA incorporated. Significant BSA release could be detected for up to 26 days.     

Bioactive glass microspheres as reinforcement for improving the mechanical properties and biological performance of poly(ε-caprolactone) polymer for bone tissue regeneration

This study examined the utility of sol-gel-derived bioactive glass microspheres (BGMs) as a reinforcement to improve the mechanical properties and biological performance of poly(ε-caprolactone) (PCL) polymer. All of the PCL-BGMs composites produced, with a variety of BGMs contents (10, 20, and 30 wt %), showed a uniform distribution of the BGMs in the PCL matrix, particularly owing to their spherical shape and small size. This led to a considerable increase in the elastic modulus from 93 ± 12 MPa to 635 ± 179 MPa with increasing BGMs content from 0 to 30 wt %. Furthermore, the addition of the BGMs to the PCL polymer significantly increased the hydrophilicity of the PCL-BGMs composites, which led to a higher water absorption and degradation rate. The PCL-BGMs composite with a BGMs content of 30 wt % showed vigorous growth of apatite crystals with a high aspect ratio on its surface after soaking in the simulated body fluid for 7 days, resulting in the creation of a porous carbonate hydroxyapatite layer.     

Degradation and drug release property of star poly(epsilon-caprolactone)s with dendritic cores

A series of star poly(epsilon-caprolactone)s (PCL) with dendritic cores, PAMAM-PCLs, were synthesized through the ring-opening polymerization of epsilon-caprolactone (CL) initiated by poly(amidoamine) dendrimer (PAMAM-OH). By controlling the feed ratio of the macroinitiator PAMAM-OH to the monomer CL, the star polymers with different branch lengths and properties can be obtained. The successful incorporation of PCL sequences onto the PAMAM-OH core was verified by FTIR, 1H NMR, and combined size-exclusion chromatography and multiangle laser light scattering analysis. The in vitro degradation of PAMAM-PCLs was investigated. The results show the hydrolytic degradation rate increases with increasing content of hydrophilic PAMAM-OH core. While the enzymatic degradation rate is affected by two competitive factors, the catalytic effect of Pseudomonas cepacia lipase on the degradation of PCL branches and the hydrophilicity that depends on the polymer composition. Using the PAMAM-PCLs with different molecular weights, the microsphere drug delivery systems with submicron sizes were fabricated using an "ultrasonic assisted precipitation method." The in vitro drug release from these microspheres was investigated.     

Preparation of Budesonide-Loaded Polycaprolactone Nanobeads by Electrospraying for Controlled Drug Release

Corticosteroids such as budesonide are the drugs of choice for the treatment of inflammatory disorders with an inherent limitation, viz., rapid elimination. To overcome this constraint and attain sustained release, budesonide was encapsulated in a biodegradable polymer, polycaprolactone (PCL), by DC electrospraying. By varying the experimental parameters involved in electrospraying such as applied voltage, flow rate, viscosity as well as conductivity of the polymer solution, the dimensionality of nanostructures was tuned from 1-D nanofibers to spherical nanoparticles. By adopting this rapid and viable method of DC electrospraying, we successfully prepared aqueous suspensions of nearly monodispersed, nano-sized drug encapsulated PCL. Drug encapsulation efficiency, in vitro drug release as well as biocompatibility studies of budesonide-loaded PCL nanobeads were carried out. The cytocompatible nanobeads prepared by electrospraying exhibited good encapsulation efficiency (approx. 75%), with controlled drug release enabled by the dissolution of the polymer. Our results demonstrate the potential of this novel technique of electrospraying in developing efficient drug encapsulated polymeric nanocarriers possessing sustained drug release profile.     

Preparation and characterization of bioactive calcium silicate and poly(epsilon-caprolactone) nanocomposite for bone tissue regeneration

A novel biocomposite of nanosized calcium silicate (n-CS) and poly(epsilon-caprolactone) (PCL) was successfully fabricated directly using n-CS slurry, not dried n-CS powder, in a solvent-casting method. The in vitro bioactivity of the composite was evaluated by investigating the apatite-forming ability in simulated body fluid. A proliferation assay with mouse L929 fibroblasts was used to test the in vitro biocompatibility. The composition, hydrophilicity, and mechanical properties were also evaluated. Results suggest that the incorporation of n-CS could significantly improve the hydrophilicity, compressive strength, and elastic modulus of n-CS/PCL composites, with the enhancements mainly dependent on n-CS content. The n-CS/PCL composites exhibit excellent in vitro bioactivity, with surface apatite formation for 40% (w/w) n-CS (C40) exceeding that of 20% (w/w) n-CS (C20) at 7 and 14 days. The Ca/P ratios of apatite formed on C20 and C40 surfaces were 1.58 and 1.61, respectively, indicating nonstoichiometric apatite with defective structure. Composites demonstrated significantly better cell attachment and proliferation than that of PCL alone, with C40 demonstrating the best bioactivity. The apatite layers that formed on the composite surfaces facilitated cell attachment (4 h) and proliferation during the early stages (1 and 4 days). Collectively, these results suggest that the incorporation of n-CS produces biocomposites with enhanced bioactivity and biocompatibility.     

A novel scaffold based on formation and agglomeration of PCL microbeads by freeze-drying

Polycaprolactone (PCL) scaffolds were prepared by freeze-drying of polymer solutions in tetrahydrofuran. Effects of the polymer composition, which is 10 and 20% (w/v), on the scaffold properties for example, morphology, porosity, mechanical stability, degradability, and so forth were investigated by using suitable methods. Scanning electron microscopy photographs clearly showed the presence of a porous, three-dimensional structure including agglomerated PCL microspheres. Porosity analysis demonstrated that 10 and 20% (w/v) scaffolds have 95.9% and 74.4% porosity, respectively. The microspheres have very narrow size distribution and their diameters increase from 50-70 microm to 90-100 microm with increasing PCL content from 10 to 20% (w/v). The microspheres were highly connected with each other and the scaffolds have superior mechanical properties when compared with the traditional PCL scaffolds. Cell culture experiments showed that periodontal ligament cells (PDL) were able to attach and proliferate on the 20% PCL scaffold. The results demonstrated that this novel PCL structure will be a potential tissue engineering scaffold with its superior properties and simple preparation procedure.     

Preparation and characterization of novel poly(ε-caprolactone)/biphasic calcium phosphate hybrid composite microspheres

Desirably porous biodegradable hybrid composite microspheres were fabricated for use in bone graft and bone substitute applications. In this study, novel poly(ε-caprolactone)/biphasic calcium phosphate (70/30) composite microspheres (PCL/BCP MPs) were prepared using the emulsion solvent-evaporation method. Throughout this process, the ammonium bicarbonate (NH?HCO?) content was changed to obtain the desired porous structure. However, to maintain the spherical shape, the NH?HCO? content should not be higher than 5%. In the optical images of the PCL/BCP MPs, almost all the microparticles had a spherical shape, and the average diameter was about 600 μm. The scanning electron microscopy and cross-sectional optical images showed that the pore density and pore diameter of PCL/BCP MPs increased with increasing initial NH?HCO? concentrations. In the phase-composition analysis of the PCL/BCP MPs, which was characterized by X-ray diffraction and EDS, the two crystals BCP and PCL phases were shown to be miscible in PCL/BCP MPs. When the degradation of these microspheres was characterized, PCL/BCP MPs-0, PCL/BCP MPs-2, and PCL/BCP MPs-5 were found to display a sustained biodegradability, and the rate of degradation increased at higher initial NH?HCO? concentrations. Proliferation of cells on three different sample types was assessed and compared, and based on these results, the PCL/BCP MPs-5 was chosen to study MG-63 osteoblast-cell adhesion, growth, and proliferation. Furthermore, confocal images indicated that the cells effectively adhered, spread, and proliferated on PCL/BCP MPs-5 during a 5-day culture period.     

Structure and Properties of Poly(ε‐caprolactone) Networks with Modulated Water Uptake

Summary: A PCL macromonomer was obtained by the reaction of PCL diol with methacrylic anhydride. The effective incorporation of the polymerizable end groups was assessed by FT‐IR and ¹H NMR spectroscopy. PCL networks were then prepared by photopolymerization of the PCL macromonomer. Furthermore, the macromonomer was copolymerized with HEA, with the aim of tailoring the hydrophilicity of the system. A set of hydrophilic semicrystalline copolymer networks were obtained. The phase microstructure of the new system and the network architecture was investigated by DSC, IR, DMS, TG, dielectric spectroscopy and water sorption studies. The presence of the hydrophilic units in the system prevented PCL crystallization on cooling; yet there was no effect on the glass transition process. The copolymer networks showed microphase separation and the α relaxation of the HEA units moved to lower temperatures as the amount of PCL in the system increased.

Ideal structure, compatible with the experimental results, for the hydrophilized poly(ε‐caprolactone) networks with modulated water uptake.     

Electrospraying: a facile technique for synthesis of chitosan-based micro/nanospheres for drug delivery applications

Electrospraying is a novel technique for the generation of micro/nanospheres for biomedical applications. Apart from being a high yield technique; electrospraying has an added advantage of not making use of an external dispersion/emulsion phase which often involves ingredients that are undesirable for biomedical applications. In this study, we report the use of electrospraying for the synthesis of chitosan micro/nanospheres. The focus was to optimize the fabrication parameters involved in electrospraying for reproducible synthesis of chitosan based micro/nanospheres and to study their potential as delivery vehicles for bioactive agents. The influence of the following was studied (i) electrospraying voltage, (ii) needle gauge, (iii) concentration of chitosan solution, (iv) concentration of acetic acid solution, and (v) electrospraying distance. SEM analysis demonstrated that microspheres of less than 1 mum were obtained when chitosan concentration was 2% dissolved in 90% acetic acid. The working distance and needle gauge that yielded favorable results were 7 cm and 26 g, respectively. Average particle size of ampicillin loaded chitosan micro/nanospheres was 520 nm with zeta potential of +28.2 mV and encapsulation efficiency of 80.4%. The particles were characterized for drug release kinetics and results demonstrated an initial burst release followed by a sustained release over a period of 120 h. Further, antibacterial activity of drug loaded micro/nanospheres demonstrated that the encapsulated drug was in its active form postexposure to high voltage during electrospraying. This study indicates that electrospraying is a facile technique for the synthesis of chitosan micro/nanospheres for drug delivery applications.