合成聚合物Kartogenin/Pluronic F127胶束与骨髓间充质干细胞的成骨分化

背景:小分子药物Kartogenin是Smad4/Smad5通路激活剂,拥有极强的促骨分化能力,可促进骨髓间充质干细胞定向分化为成骨细胞,但其药物效果较为局限。目的:设计并研制Kartogenin/Pluronic F127胶束,观察其对骨髓间充质干细胞定向成骨分化的作用。方法:将小分子药物Kartogenin溶于二甲基亚砜中,然后与Pluronic F127溶液混合均匀,通过真空旋转蒸发仪去除有机溶剂购形成一干燥的药脂膜,加入PBS制备为Kartogenin/Pluronic F127胶束。取对数生长期的大鼠骨髓间充质干细胞,分4组处理,分别加入常规细胞培养液(空白组)、含Pluronic F127胶束溶液的细胞培养液(Pluronic F127组)、含Kartogenin的细胞培养液(药物组)、含Kartogenin/Pluronic F127胶束溶液的细胞培养液(实验组),其中药物组与实验组中药物浓度均为1μmol/L,Pluronic F127组与实验组胶束浓度一致。检测细胞增殖、凋亡及成骨相关蛋白表达。结果与结论:①透射电镜显示Kartogenin/Pluronic F127胶束呈现出不规则的球状形态,粒径分布较为均匀,粒径范围为32.6-118.9 nm,多集中在77.3 nm;②MTT检测显示,随着培养时间的延长,4组细胞存活率下降,但均保持在90%以上,4组间细胞生存率比较差异无显著性意义(P>0.05);③处理24 h后的流式细胞仪检测显示,4组间的细胞凋亡率比较差异无显著性意义(P>0.05);④处理24 h后的Western blot检测显示,药物组、实验组的骨桥蛋白、碱性磷酸酶、骨形态发生蛋白2及基质金属蛋白酶2表达均高于Pluronic F127胶束组、空白组(P<0.05),实验组的碱性磷酸酶、骨形态发生蛋白2及基质金属蛋白酶2表达高于药物组(P<0.05);⑤结果表明,Kartogenin/Pluronic F127胶束可促进骨髓间充干细胞的成骨分化。

Docetaxel-loaded mixed micelles composed of Solutol HS15 and Pluronic F127 or folate-conjugated F127: preparation, optimization and in vitro comparative characterization

In this study, two kinds of docetaxel （DTX）-loaded mixed micelles, composed of Solutol HS15 （HS 15）/Pluronic F127 （F 127） or folate-conjugated F127, （SF-DTX and FSF-DTX）, were prepared by the thin-film hydration method and evaluated in vitro. Both SF-DTX and FSF-DTX were spherical with diameter close to 23 nm. They had high encapsulating efficiency （99.05% and 90.28% for SF-DTX and FSF-DTX, respectively） and sustained-release property. SF and FSF were able to enhance the cellular accumulation of DTX in KBv cells and reduce ATP content in A-549 cells. They also were able to reverse multidrug resistance （MDR）. In vitro cytotoxicity and cellular accumulation of DTX suggested an active targeting of FSF-DTX. It could be concluded from the results that the novel F 127/HS 15 system could serve as a potential nanocarrier with the ability of overcoming MDR, and folate-conjugated F 127/HS 15 might achieve active targeting at the same time.

Pulmonary delivery of mucus-traversing PF127-modified silk fibroin nanoparticles loading with quercetin for lung cancer therapy

The mucosal barrier remains a major barrier in the pulmonary drug delivery system,as mucociliary clearance in the airway accelerates the removal of inhaled nanoparticles(NPs).Herein,we designed and developed the inhalable Pluronic F127-modified silk fibroin NPs loading with quercetin(marked as QR-SF(PF127)NPs),aiming to solve the airway mucus barrier and improve the cancer therapeutic effect of QR.The PF127 coating on the SF NPs could attenuate the interaction between NPs and mucin proteins,thus facilitating the diffusion of SF(PF127)NPs in the mucus layer.The QR-SF(PF127)NPs had particle sizes of approximately 200 nm with negatively charged surfaces and showed constant drug release properties.Fluorescence recovery after photobleaching(FRAP)assay and transepithelial transport test showed that QR-SF(PF127)NPs exhibited superior mucus-penetrating ability in artificial mucus and monolayer Calu-3 cell model.Notably,a large amount of QR-SF(PF127)NPs distributed uniformly in the mice airway section,indicating the good retention of NPs in the respiratory tract.Themicemelanoma lungmetastasismodel was established,and the therapeutic effect of QR-SF(PF127)NPs was significantly improved in vivo.PF127-modified SF NPs may be a promising strategy to attenuate the interaction with mucin proteins and enhancemucus penetration efficiency in the pulmonary drug delivery system.

Effects of F127 on Properties of PVB/F127 Blend Hollow Fiber Membrane via Thermally Induced Phase Separation

Hydrophilic poly(vinyl butyral)(PVB) /Pluronic F127(F127) blend hollow fiber membranes were prepared via thermally induced phase separation(TIPS) ,and the effects of blend composition on the performance of hydrophilic PVB/F127 blend hollow fiber membrane were investigated.The addition of F127 to PVB/polyethylene glycol(PEG) system decreases the cloud point temperature,while the cloud point temperature increases slightly with the addition of F127 to 20%(by mass) PVB/F127/PEG200 system when the concentration of F127 is not higher than 5%(by mass) .Light scattering results show that the initial inter-phase periodic distance formed from the phase separation of 20%(by mass) PVB/F127/PEG200 system decreases with the addition of F127,so does the growth rate during cooling process.The blend hollow fiber membrane prepared at air-gap 5mm,of which the water permeability increases and the rejection changes little with the increase of F127 concentration.For the membrane prepared at zero air-gap,both water permeability and rejection of the PVB/F127 blend membrane are greater than those of PVB membrane,while the tensile strength changes little.Elementary analysis shows that most F127 in the polymer solution can firmly exist in the polymer matrix,increasing the hydrophilicity of the blend membrane prepared at air-gap of 5mm.

源自嗜热菌的α-L-鼠李糖苷酶交联聚集体的制备及应用

研究了一种制备嗜热菌Thermotoga petrophila DSM 13995来源的α-L-鼠李糖苷酶交联聚集体的方法。试验结果表明:在酶蛋白与Pluronic F127质量比为1∶8、沉淀剂硫酸铵质量浓度为75 mg/mL、戊二醛浓度为40 mmol/L时固定α-L-鼠李糖苷酶,酶活回收率可达49.45%。以硫酸铵-戊二醛(CLEA)的常规顺序制备固定化酶(PAG-R)时,酶活回收率仅为30.87%,而在Pluronic F127-硫酸铵-戊二醛(PL-AS-GL)顺序下制备PAG-R,酶活回收率达到60.90%,固定化剩余酶活力为34 U/mL。此外,研究了固定化酶PAG-R的酶学性质,结果表明PAG-R的最适温度为90℃,最适pH为5.0,与游离酶TpeRha的酶学性质相近,但在不同温度和pH条件下PAG-R的比酶活更高。PAG-R在90℃保温3 h后剩余酶活力为77.11%,而游离酶TpeRha则完全丧失活力,说明固定化酶的温度稳定性得到了较大的提升。以芦丁为底物,比较了PAG-R与TpeRha催化芦丁生成异槲皮素的产率差异。在温度80℃、pH 6.5、加酶量4 U/mL、反应时间90 min时,PAG-R能完全转化3 g/L底物,摩尔转化率为100%,产物的生成量是游离酶的2.31倍。连续反应10次后,芦丁相对转化率仍能保持在60%以上,由此可知固定化后的鼠李糖苷酶其催化效率得到了提高,且重复使用性能良好,更有利于工业化应用。

3D纳米纤维海绵的制备及吸油性能研究

为研发环保型高效吸油材料,以可完全生物降解的聚己内酯(PCL)为主体原料,添加Pluronic F127为改性剂,采用静电纺丝技术与气体发泡技术相结合的方式,制备了具备3D蓬松多孔结构的纳米纤维海绵。探究了不同Pluronic F127含量对3D纳米纤维海绵成形及其性能的影响。结果表明:所制备的纳米纤维海绵具备三维结构,存在明显的纳米纤维层;随着Pluronic F127含量的增加,3D纳米纤维海绵的膨胀高度呈现增大的趋势,但含量过高会导致海绵结构松散、软塌;与未膨胀的2D纳米纤维膜相比,3D纳米纤维海绵的吸油倍率显著提升,对于硅油、豆油等油类的吸油倍率是纳米纤维膜的2倍~3倍。当Pluronic F127含量为PCL质量的4%时,3D纳米纤维海绵的吸油性能较理想,吸油倍率可达到30 g/g~40 g/g。

The potential of starch-chitosan blends with poloxamer for the preparation of microparticles by spray-drying

Using biopolymers as wall materials in spray drying poses challenges,particularly in attaining flowability and thermal stability among their physicochemical properties.This paper addresses these challenges by preparing microparticles using a blend of starch–chitosan and a poloxamer,commercially named Pluronic®F127.We aimed to elucidate the effects of varying poloxamer concentrations on the resulting particles through the spray drying technique.Blends with a poloxamer concentration of 3%(w/v)demonstrated a notably higher yield,especially when compared to those with 0%and 1%concentrations.Microparticles with 3%and 5%(w/v)poloxamer displayed a narrower particle size distribution,with the 3%blend showing a superior yield attributed to arrangements of blend components that improve flowability.X-ray diffraction analysis showcased the characteristic peaks of A-type starch form,with shifts suggesting enhanced interactions between components.Microparticles with increased poloxamer content showed elevated thermal degradation temperatures,with the 3%blend registering a significant rise,opening avenues for encapsulating heat-sensitive bioactive.This study primarily focuses on the preparation and basic characterization of microparticles.It underscores the potential of blends with optimal poloxamer concentrations in microencapsulation,emphasizing further research to harness their capabilities thoroughly.