Injectable muscle-adhesive antioxidant conductive photothermal bioactive nanomatrix for efficiently promoting full-thickness skeletal muscle regeneration

The completed skeletal muscle regeneration resulted from severe injury and muscle-related disease is still a challenge.Here,we developed an injectable muscle-adhesive antioxidant conductive bioactive photothermo-responsive nanomatrix for regulating the myogenic differentiation and promoting the skeletal muscle regeneration in vivo.The multifunctional nanomatrix was composed of polypyrrole@polydopamine(PPy@PDA,342±5.6 nm)nanoparticles-crosslinked Pluronic F-127(F127)-polycitrate matrix(FPCP).The FPCP nanomatrix demonstrated inherent multifunctional properties including excellent photothermo-responsive and shear-thinning behavior,muscle-adhesive feature,injectable ability,electronic conductivity(0.48±0.03 S/m)and antioxidant activity and photothermal function.The FPCP nanomatrix displayed better photothermal performance with near-infrared irradiation,which could provide the photo-controlled release of protein(91%±2.6%of BSA was released after irradiated 3 times).Additionally,FPCP nanomatrix could significantly enhance the cell proliferation and myogenic differentiation of mouse myoblast cells(C2C12)by promoting the expressions of myogenic genes(MyoD and MyoG)and myosin heavy chain(MHC)protein with negligible cytotoxicity.Based on the multifunctional properties,FPCP nanomatrix efficiently promoted the full-thickness skeletal muscle repair and regeneration in vivo,through stimulating the angiogenesis and myotube formation.This study firstly indicated the vital role of multifunctional PPy@PDA nanoparticles in regulating myogenic differentiation and skeletal muscle regeneration.This work also suggests that rational design of bioactive matrix with multifunctional feature would greatly enhance the development of regenerative medicine.

Controlled Growth of CdS Nanocrystals: Core/Shell viz Matrix

The ability to precisely control the size of semiconductor nanocrystals can create an opportunity for producing functional materials with new properties, which are of importance to applications such as Light emitting diodes, biomedical diagnosis, solar cells, and spintronics. And size of nanoparticle can be controlled with efficient capping agent. For the same purpose we reported, two types of capping, one will lead to nanomatrix and other to Shelled nanostructures. Enhancement in emission intensity observed with Shell nanostructures compare to matrix. PVP is used to control the particle size, to prevent agglomeration and making thin films. A blue shift in energy level at the nanoscale is demonstrated by optical absorption. Electron microscopy studies with an SEM and TEM show a particle size of 10 nm and 15 nm. We also investigated the particle size distribution of nanoparticles by small angle scattering (SAXS) study.

经口给予纳米骨架系统中载体荷电性对缬沙坦体外释放的影响

目的考察经口给予纳米骨架给药系统中载体的荷电性对荷电药物缬沙坦体外释放的影响,以期寻找到经口给予纳米骨架给药系统中荷电药物的释放规律。方法采用溶剂挥发法制备不同处方的口服纳米骨架给药系统,用桨板法测定药物释放度,应用X射线衍射法、扫描电镜法、透射电镜法和红外吸收光谱法对其进行表征。结果调节载体材料种类和比例可以控制药物释放速度和程度。当药物与载体带有相反电荷时,加入电解质使药物释放增加;当药物与载体带有相同电荷时,加入电解质使药物释放减少。结论药物与载体之间的电荷作用对经口给予纳米骨架系统中药物的体外释放行为具有重要的影响,可为制备荷电药物的经口给予纳米骨架系统提供参考。

氟灭酸对索拉菲尼纳米骨架给药系统中索拉菲尼溶解度、溶出度和体内药动学行为的影响

考察氟灭酸(flufenamic acid, FFA)对索拉非尼纳米骨架给药系统[sorafenib loaded nanomatrix drugdelivery system (MSNM@SFN)]中索拉菲尼(sorafenib, SFN)的溶解度、溶出度和体内药动学行为的影响。先制备MSNM@SFN,再与FFA物理混合,制备索拉菲尼纳米骨架给药系统联合氟灭酸(MSNM@SFN&FFA),考察MSNM@SFN&FFA中SFN的溶解度、溶出度和大鼠体内药动学行为,并与前期MSNM@SFN的相应数据进行比较,以确定FFA对MSNM@SFN中SFN的溶解度、溶出度和体内药动学行为的影响。动物实验动物实验均按照国际动物实验指导原则进行并被北京大学医学部实验动物中心伦理学委员会批准。结果表明,与MSNM@SFN相比, MS‐NM@SFN&FFA中SFN的溶解度、溶出度和大鼠体内药动学行为等无明显改变,说明MSNM@SFN与FFA混合后,FFA对SFN在MSNM@SFN中的溶解度、溶出度以及大鼠体内生物利用度等都无显著影响,为后续两药联用的制剂研究提供科学依据。

缬沙坦纳米骨架系统在大鼠体内的药动学研究

目的采用HPLC法研究缬沙坦纳米骨架系统在SD大鼠体内的生物利用度。方法采用BDS Hypercil C18柱(250mm×4.6 mm,5μm);流动相:甲醇–乙腈–0.01 mol/L磷酸二氢钾(44∶24∶32);体积流量1.0 mL/min;检测波长250 nm;柱温30℃;进样量20μL。取雄性SD大鼠12只,随机分为2组,按照缬沙坦20 mg/kg分别ig缬沙坦胶囊和缬沙坦纳米骨架系统,绘制血药浓度–时间曲线,采用DAS 2.1.1软件计算主要动力学参数Cmax、tmax、AUC、F。结果缬沙坦在0.481~48.1μg/mL线性关系良好。定量限为0.4μg/mL,准确度、灵敏度、精密度和专属性均符合体内分析方法学要求。缬沙坦纳米骨架系统药时曲线下面积比缬沙坦胶囊提高154.78%,显著提高缬沙坦的体内生物利用度。结论缬沙坦纳米骨架系统血药浓度变化相对较为平缓,有望成为难溶性药物的新型给药方式。

热熔挤出法制备的非诺贝特纳米骨架系统的体外释放和口服生物利用度研究（英文）

溶剂挥发法制备纳米骨架具有有机溶剂残留、环境污染、需要防爆保护等缺点。本文使用多孔二氧化硅Sylysia~?350(S350)和pH敏感材料Eudragit~?L100-55(EL100-55)采用热熔挤出法(HME)制备了一系列的非诺贝特纳米骨架给药系统,并比较了它们的体外溶出及体内生物利用度,最后选择体内生物利用度最高的处方,进行DSC和PXRD的表征。结果表明,尽管纳米骨架系统中仍然存在结晶态的药物,但其相对于市售制剂依然有着更好的溶出速率和更高的大鼠口服生物利用度。与市售制剂相比,最优化处方的口服生物利用度是市售制剂的157.1%;与溶剂挥发法相比,最优化处方的口服生物利用度是溶剂挥发法的124.8%,热熔挤出法制备的纳米骨架在提高生物利用度方面更具优势。总之,热熔挤出法也可以作为制备纳米骨架给药系统的一种选择。