功能聚乳酸改性羟基磷灰石有机无机复合材料的制备

随着科技的进步,医学水平在不断提高,医用材料越来越受到广泛的重视,其中利用人工骨替代材料来修复、替代骨缺损成为医学骨科领域的研究重点。首先在羟基磷灰石表面引入活性醛基,通过活性醛基将聚乳酸基聚合物接枝到羟基磷灰石表面,改善羟基磷灰石与聚合物复合时,分布不均,相界面结合不牢的缺点,再将经过聚乳酸基聚合物改性的羟基磷灰石与聚乳酸-羟基乙酸共聚物通过超重力技术强力混合,制备骨修复材料。复合材料的吸水率为2.9%,拉伸强度为52.62 MPa,弯曲强度为87.348 MPa。     

PLGA基载药复合微球的制备及其释放性能

以聚乳酸-羟基乙酸(PLGA)为载体材料,牛血清蛋白(BSA)为蛋白模型药物,采用复相乳化溶剂法制备PLGA载药微球,探索载药微球制备过程中囊芯比、初乳水油比、分散剂浓度、超声乳化时间对微球粒径大小、载药率、包封率的影响。结果表明,最优载药微球的制备条件为:囊芯比1:1,初乳水油比3:5,分散剂质量分数0.5%,超声乳化时间2 min。在此条件下,所得PLGA微球的粒径为268.7 nm,载药率30.88%,包封率46.95%; 电镜照片表明微球表面连续光滑,粒径分布较均匀。采用静电吸附法用阳离子聚电解质壳聚糖对最佳条件下的PLGA载药微球进行表面修饰,扫描电镜表明复合后微球粒径变大,能谱分析表明复合后微球中有N元素存在,即复合微球中存在壳聚糖,电荷测试表明微球表面带正电; 体外释放实验表明PLGA-CS复合载药微球的缓释时间延长,释药初期的突释性明显改善。     

阿霉素微胶囊的制备及表征

采用三嵌段共聚物聚乳酸-聚乙二醇-聚乳酸（PLA-PEG-PLA）为载体,阿霉素为模型药物,通过双乳化溶剂蒸发法制备出阿霉素微胶囊,考察了稳定剂和制备条件对阿霉素微胶囊的性质及阿霉素的载药率和释放速率的影响。扫描电子显微镜和激光粒度测试表明,阿霉素微胶囊呈类球形或不完全球形,粒径大小为900nm左右。阿霉素微胶囊对阿霉素的包封率为35.7％。通过体外释药实验表明,阿霉素微胶囊可持续释药10天以上。     

壳聚糖亚微粒稳定的Pickering乳液制备pH响应微胶囊

采用离子凝胶法制备了壳聚糖-三聚磷酸钠(CS-TPP)亚微米颗粒,并以其为稳定剂,制备了内含聚乳酸-羟基乙酸共聚物(PLGA)和布洛芬(IBU)药物的o/w型Pickering乳液;采用溶剂挥发法制备了CS-TPP亚微米颗粒包覆的载药微胶囊,并通过静电作用包覆羧甲基纤维素钠(CMC).利用SEM、光学显微镜、荧光共聚焦显微镜、红外光谱等对载药微胶囊进行了表征.以IBU为模型药物,在模拟胃液(SGF,pH=1.2)和模拟肠液(SIF,pH=6.8)中进行载药微胶囊的体外药物释放实验.结果表明:所得载药微胶囊在SIF中释放速率为其在SGF中的约12倍,表现出良好的pH响应性.     

高分子量聚乳酸-羟基乙酸共聚物的合成

研究一种实验室高分子量聚乳酸-羟基乙酸共聚物合成的新方法,探讨熔融聚合工艺参数和扩链剂对共聚物分子量的影响.以90mL乳酸和10g羟基乙酸为原料,顺丁烯二酸酐为扩链剂,探讨温度、催化剂种类、催化剂及扩链剂用量对共聚物特性黏度的影响.当熔融温度为180℃,压力为400pa,复合催化剂用量为0.4g,扩链剂用量为2g时,聚乳酸-羟基乙酸共聚物的特性黏度最好.     

可降解聚合物溶胀性能对给药系统释药效果的影响

针对以乳酸-羟基乙酸共聚物(PLGA)作为药物载体的新型贮库式微孔结构缓控释给药系统,为量化PLGA溶胀特性对释药效果的影响,在模拟体液环境下,以具有不同单体质量比的PL-GA膜片上的微孔为研究对象,对PLGA在降解过程中的溶胀现象进行了实验研究,得到单体质量比为50∶50的PLGA的微孔径向溶胀速率约为2.7×10-10 m/s,质量比为65∶35的PLGA的微孔径向溶胀速率约为6.6×10-11 m/s.以单体质量比为50∶50的PLGA为例,将实验得到的微孔溶胀速率作为边界条件,对考虑PLGA溶胀作用前、后的微孔给药系统释药过程进行了有限元模拟,结果表明:聚合物溶胀使给药系统释药时间从无溶胀时的16d延长到33d;不考虑溶胀时,PL-GA基体仅起承载药物的作用,而考虑溶胀后,微孔和PLGA基体共同承担药物释放功能,其中近40%的药物通过微孔释放,近60%的药物通过聚合物载体释放;给药系统在整个释药过程中累积释药比率线性度较好.     

新型W/O/O法BSA/PLGA微球的制备、表征及体外细胞活性的研究

选用牛血清白蛋白(BSA)为模型药物,聚乳酸-聚乙羟基醇共聚物(PLGA)为药物载体,通过水/油/油(W/O/O)新型凝聚法进行BSA/PLGA缓释微球的制备,考察PLGA的浓度、分子量、二氯甲烷(DCM)和硅油体积比、搅拌转速、固化溶剂及干燥方式等各个因素对制备过程的影响,并对其形貌、粒径、载药量和包封率等进行分析与表征,从而确定最佳的BSA/PLGA缓释微球的制备处方和工艺.结果表明:微球圆整均匀、平均粒度是75μm,包封率达85%;红外扫描图显示PLGA和BSA分子之间形成新的氢键,BSA被包裹在PLGA微球中;DSC图谱显示BSA被包裹在其中呈无定型状态;体外细胞活性实验中,3T3的细胞活性在80%以上,具有安全性.通过W/O/O新型凝聚法制备BSA/PLGA缓释微球的工艺较为稳定,包封率较高,载药量为4.58%.     

可降解药物控释系统的药物扩散系数表征

为实现药物的长期稳定释放并提高药物利用率,提出了一种以聚乳酸-聚羟基乙酸(PLGA)为载药基体的新型植入式药物控释系统。该药物控释系统可埋植在病灶附近进行长期释药,在药物释放结束后药物载体自然降解。为研究该药物控释系统的释药性能,建立其药物释放模型、模拟释药过程是有效方法之一,但在建立药物释放模型过程中,不断降解的PLGA材料特性难以量化。文中提出了一种使用扩散系数来表征PLGA材料的降解溶蚀程度的方法,在37℃下使用生理盐水模拟体液,对50/50、65/35及75/25三种单体比例的PLGA材料进行吸水实验和降解实验,并制备全封装药物控释系统进行了体外释药实验。通过实验结果的对比并基于物质守恒与传递定理,推导了封装药物在PLGA载药基体中释放时扩散系数的分段表达函数。基于该扩散系数表达函数,建立了药物通过该给药系统释放的有限元模型;使用有限元模型模拟药物的释放过程,并将有限元模拟结果与该药物控释系统体外释药实验结果进行了对比。结果表明,药物控释系统累积释药量呈线性变化,有限元模型模拟结果与体外释药实验结果基本吻合,验证了药物在PLGA材料中扩散系数分段表达式及有限元释药模型的正确性。该研究为后期建立药物释放的解析模型提供了一定的理论基础。     

多柔比星长效注射微球的评价和对小鼠肿瘤的抑制作用

主要考察了多柔比星(Dox)微球的理化性质、释放特性及其对荷瘤小鼠的抑制作用.以乳酸羟乙酸共聚物(PLGA)为载体材料,用复乳法(w/o/w)制备载Dox长效注射微球;考察粒径大小、外观、包封率、载药量等理化性质;用紫外分光光度法检测了体外释放溶液中的药物含量,以荷Lewis肺癌小鼠的肿瘤质量和体积为指标观察Dox微球(Dox-MS)瘤内注射给药后的抗肿瘤活性.制备得到的微球球形圆整、分散性好,平均粒径为82.94 μm,包封率为92.67%,载药量为9.12%.微球体外第1天释放30.24%, 20 d累积释放91.85%.给药8 d后,Dox微球瘤内注射给药组与对照组相比肿瘤平均体积明显减小,抑瘤率与对照组相比具有极显著性差异(P<0.01),但与Dox溶液静脉、瘤内给药组相比无显著性差异.因此Dox微球对小鼠体内Lewis肺癌具有较好的抑制作用,其抑瘤效果与瘤内注射相同剂量的Dox溶液相当,但局部刺激性较小.     

胶原修饰快速成形PLGA/TCP人工骨支架体外生物相容性研究

探讨经Ⅰ型胶原修饰的快速成型(RP)聚乳酸-羟基乙酸/磷酸三钙(PLGA/TCP)支架的生物相容性,为进一步体内实验提供研究基础.以经Ⅰ型胶原修饰改性的PLGA/TCP支架作为实验组,未经胶原修饰的原始支架作为对照组,检测两组支架材料的亲水性.BMSCs接种两组支架,分别测定细胞黏附率、细胞增殖率.扫描电镜(SEM)观察细胞黏附形态,以检验支架材料的细胞相容性.结果表明胶原改性支架具有较高的亲水性,实验组细胞黏附率在接种4、8和12 h者,明显优于对照组(P<0.05).实验组在培养2、4、6和8 d的细胞增殖率也明显高于对照组(P<0.05).扫描电镜可见骨髓基质细胞在实验组支架上的增殖数量多于对照组.说明Ⅰ型胶原改性的PLGA/TCP支架具有良好的细胞生物相容性,可作为骨组织工程支架应用于骨缺损的修复研究.     

利福平/OCS-PLGA纳米缓释微球的制备及体外释放性能

采用乳化溶剂蒸发法制备了油酰壳聚糖(OCS)包被的聚乙丙交酯(PLGA)纳米粒子(OCS-PL-GA NPs).采用红外光谱分析OCS-PLGA NPs.扫描电镜结果显示纳米微球形态规整、分布范围小,表面没有小孔、裂纹.PLGA浓度增大,缓释效果增强.PLGA的加入改变了疏水性内核的构造,在内核中形成网络状屏障,从而降低了药物的释放速度.OCS浓度增大,增加了纳米微球的稳定性,也增加了纳米微球外壳的厚度和致密性,增强了药物释放过程中的物理屏障,缓释效果增强.     

Y型微通道内聚乳酸-羟基乙酸共聚物纳米分散体的制备

采用Y型微通道,通过反溶剂沉淀法研究了聚乳酸-羟基乙酸共聚物(PLGA)透明纳米分散体的制备过程。实验考察了在丙酮-水体系条件下,PLGA丙酮溶液浓度、总流量、反溶剂流量、溶剂流量和温度等对PLGA纳米分散体颗粒粒径和分布的影响。研究结果表明：固定溶剂与反溶剂流量比为1：20,随着总流量从21mL/min增大到63mL/min时,颗粒粒径从178 nm减小到91 nm,而继续增大总流量到84 mL/min,粒径增大到106nm;随着反溶剂流量从2mL/min增大到16mL/min,颗粒粒径从115nm增大到141nm;此外,随着反溶剂流量和PLGA溶液浓度的增大,颗粒粒径呈先减小后增大的趋势;而随着体系温度的下降,粒径显著减小。     

PLGA/硬石复合涂层镁基纳米复合材料在植入应用时的体外生物活性和腐蚀行为

A type of polymer/ceramic coating was introduced on a magnesium-based nanocomposite, and the nanocomposite was evaluated for implant applications. The microstructure, corrosion, and bioactivity of the coated and uncoated samples were assessed. Mechanical alloying followed by sintering was applied to fabricate the Mg–3Zn–0.5Ag–15NiTi nanocomposite substrate. Moreover, different contents of poly(lactic-co-glycolic acid) (PLGA) coatings were studied, and 10wt% of PLGA content was selected. The scanning electron microscopy (SEM) images of the bulk nanocomposite showed an acceptable homogenous dispersion of the NiTi nanoparticles (NPs) in the Mg-based matrix. In the in vitro bioactivity evaluation, following the immersion of the uncoated and coated samples in a simulated body fluid (SBF) solution, the Ca/P atomic ratio demonstrated that the apatite formation amount on the coated sample was greater than that on the uncoated nanocomposite. Furthermore, assessing the corrosion resistance indicated that the coatings on the Mg-based substrate led to a corrosion current density (i_corr) that was considerably lower than that of the substrate. Such a condition revealed that the coating would provide an obstacle for the corrosion. Based on this study, the PLGA/hardystonite (HT) composite-coated Mg–3Zn–0.5Ag–15NiTi nanocomposite may be suitably applied as an orthopedic implant biomaterial.     

Preparation,Characterization, and Antitumor Efficacy of,Camptothecine-Loaded Hydroxyapatite / Poly （lactic-co,glycolic acid ） Composite Nanofibers via Electrospinning

In the past decade, various medicated nanofibrous scaffolds have been developed as effective drug delivery systems for postsurglcal cancer treatment. In this study, hydroxyapatite nanoparticles （HANPs） were used as carriers to load an anticancer （CPT）, and the CPT-Ioaded HANPs （CPT @HANPs） was then incorporated into poly（ lactic-co.glycolic acid） （PLGA） nanofibers via electrospinning. Thus fabricated medicated nanofibrous mats （ PLGA /CPT @ HANPs） were characterized by field emission scanning electron microscope （FESEM）, transmission electron microscope （TEM）, attenuated total reflection Fourier transform infrared spectroscopy （ATR-FTIR） and X-ray diffraction （XRD）. The release prof＇des of CPT from the medicated electrospun mats were obtained and their in vitro anticancer efficacy against HeLa cells was also evaluated. The results showed that the CPT was successfully loaded onto the surface of HANPs, and the prepared electrospun mats exhibited a homogeneous and continuous morphology. Furthermore, the loaded CPT exhibited a sustained release behavior from the nanoflbrous mats and the released CPT showed a long-term anticancer efficacy against HeLa cells. Therefore, the prepared medicated electrospun mats may be served as an effective drug delivery device for local antitumor treatment.     

In vitro study of poly(ethylene carbonate) as a drug-eluting stent coating

An in vitro feasibility study of the use of poly(ethylene carbonate) (PEC) as a biodegradable coating material for drug-eluting stents is reported, and the performance of PEC is compared with that of poly(lactic-co-glycolic acid) (PLGA). Scanning electron microscopy (SEM) images of PEC and PLGA discs after treatment with an alkaline KO2 solution as a superoxide source showed that the PEC maintained its integrity whereas holes and small particles appeared during the treatment of PLGA. Sirolimus and paclitaxel were loaded into PEC and PLGA in order to study drug release performance. Attenuated total reflectance–infrared (ATR– FTIR) spectroscopy of sirolimus, PEC and the sirolimus-loaded PEC coating showed that no chemical reaction occurred between sirolimus and PEC. The results of atomic force microscopy (AFM) revealed that the mean roughness (Ra) values of the bare metal stent (BMS) and the drugeluting stent (DES) were 2.3 nm and 1.0 nm, respectively. After balloon expansion experiments, no delamination or destruction of the PEC coating was observed. The drug release profile of sirolimus was different from that of paclitaxel when PEC was employed as the drug carrier, and the release curves of sirolimus were different when PEC and PLGA were used as drug carriers. All the experimental results demonstrated that PEC was one of the best potential stent-coating materials.     

乙醇为溶剂超临界干燥法制备纳米Al2O3

以硝酸铝为原料,柠檬酸为分散剂,无水乙醇为溶剂,采用溶胶-凝胶结合超临界干燥的方法制备了纳米AlOOH。经过500～900℃焙烧后得到纳米γ-Al₂O₃。考察了溶液pH值、硝酸铝与柠檬酸物质的量比对AlOOH粉体,以及焙烧温度对γ-Al₂O₃两者形貌和尺寸的影响。采用TEM、XRD、IR对超细粒子的粒径、形貌进行了表征。结果表明,制备溶胶时的pH值和柠檬酸的〖JP2〗加入对经超临界干燥所得的AlOOH的形貌和尺寸有明显影响。在pH=3,n(C₆H₈O₇)∶n(Al(NO₃)₃)=1∶2的条件下可得到纤维状纳米AlOOH(直径为1～10nm, 长为30～40nm)。该AlOOH经500～900℃焙烧后可得纤维状纳米γ-Al₂O₃,其直径为1～10nm,长为30～70nm。     

Preparation and mineralization of PLGA/Gt electrospun fiber mats

Poly(lactic-co-glycolic acid)(PLGA)/gelatin(Gt) ultrafine composite fibers were fabricated via electro-spinning.The effect of gelatin on the morphology and tensile property of the electrospun fiber mats was investigated.Mineralization was carried out in 10×simulated body fluid(10SBF).The deposited calcium phosphate(CaP) was identified by scanning electron microscopy(SEM),energy dispersive spectroscopy(EDS),X-ray diffraction(XRD) and Fourier transform infrared spectroscopy(FTIR).Results indicated that the av...     

水杨酸在含夹带剂的超临界CO2中的溶解度

采用流动法测定和研究了水杨酸在308K,328K下,100～250MPa范围内,在纯超临界CO₂和环己烷、丙酮及乙醇做夹带剂的超临界CO₂中的溶解度。实验数据表明三种夹带剂的加入均增大了水杨酸在SC-CO₂中的溶解度,其增大幅度依次为环己烷、乙醇和丙酮。文中论述了温度、压力对溶解度的影响,对三种夹带剂的“提携”作用机理进行了分析,并用Sovova方程对实验数据进行了回归,得到了较满意的结果.     

Distribution of bone marrow stem cells in large porous polyester scaffolds

This work examined the optimal syringing depth during in vitro cell loading in order to even cell distribution after syringing a drop of cell suspension in cylinder poly（lactide-co-glycolide） （PLGA） porous scaffolds. The scaffolds of 10 mm height and 10 mm diameter were fabricated via room-temperature compression molding ＆ particulate leaching technique based on spherical porogens. In vitro tests were employed for such examinations： a global observation of a cell-loaded scaffold stained by the 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide （MTT） technique and a quantitative measurement of spatial distribution of cells after slicing the cell-loaded scaffolds into layers. It was found that an even distribution of cells was soon achieved only if the initial cell suspension was seeded on the layer that was below the top surface but above the middle of scaffolds. The availability of in vitro osteoblastic differentiation of rat bone marrow stem cells in such a kind of spherical-pore PLGA scaffolds was meanwhile confirmed.     

影响USFE萃取海藻EPA和DHA的因素分析

研究了萃取温度、压力、时间、CO2流量和超声参数对超声强化超临界流体萃取海藻EPA和DHA的影响,发现与超临界流体萃取相比,超声强化超临界流体萃取过程使CO2流量减小,萃取温度及压力降低,萃取时间缩短,而EPA和DHA的萃取率提高,在单因素实验的基础上进行了正交实验,结果表明,超声强化超临界流体萃取EPA和DHA的最佳工艺条件为：萃取温度35℃,压力25MPa,时间3．0h,CO2流量3L／h。