新型姜黄素纳米胶束滴眼液的制备及体内外性质研究

目的 制备新型姜黄素纳米胶束滴眼液,检测其理化性质,并观察其生物学性质.方法 通过溶剂蒸发·水化法制备姜黄素纳米胶束滴眼液,分别测定其粒径、包封率和稳定性;通过眼局部刺激实验方法考察纳米胶束的细胞毒性和细胞摄取作用;采用眼局部刺激实验方法测定姜黄素纳米胶束滴眼液的体内眼局部刺激性;以兔眼表给予花生四烯酸溶液建立眼局部炎症模型,评价纳米胶束的抗炎活性.结果 使用聚己内酰胺一聚乙酸乙烯酯一聚乙二醇聚合物成功构建姜黄素纳米胶束滴眼液,粒径为(50.1±1.0)nm,包封率为(99.37±0.76)％;储存稳定性分析结果显示,12周后储存在4℃质量比为18:1的姜黄素纳米胶束滴眼液药物含量仍有(98.13±0.97)％,而质量比15:1的药物含量为(89.32±1.59)％.25℃条件下的实验结果与4℃结果相似,因此最佳处方质量比为18:1.制备的姜黄素纳米胶束呈橙红色透明状,优化处方后的纳米胶束粒径、多分散系数和Zeta电位分别为(50.1±1.0)nm、0.079±0.011和-(1.83±0.67)mY,包封率为(99.37±0.76)％.姜黄素溶液在pH6.0至pH7.4的不同条件下,降解速度分别是对应姜黄素纳米胶束降解速度的24.9倍、28.4倍、44.8倍、73.7倍、315.0倍和662.1倍.体外细胞实验结果显示浓度为500.00μg·mL-1的姜黄素纳米胶束孵育细胞48 h后,细胞存活率为86.89％;4.5 mg·mL-1姜黄素纳米胶束滴眼液孵育细胞lh后未发现细胞毒性.兔眼局部刺激性实验结果显示,姜黄素纳米胶束滴眼液、玻璃酸钠滴眼液(1mg·mL-1)和空白PBS 3组实验在不同时间点的临床评分均在0～2的范围内,属于无刺激性等级.体内角膜渗透性结果显示,姜黄素纳米胶束组的荧光强度均显著强于姜黄素溶液组.抗炎活性结果显示姜黄素纳米胶束表现出显著的剂量依赖性抗炎活性.结论 局部聚合物构建的姜黄素纳米胶束滴眼液显著改善了姜黄素的体内外及生物学性质,有望开发成为一种新型有效的眼用姜黄素制荆.     

Optimization of a dry powder inhaler of ciprofloxacin-loaded polymeric nanomicelles by spray drying process

Ciprofloxacin is a commonly prescribed antibiotic for treatment of pulmonary infections. Nanocarriers such as nanomicelles can increase the drug residence time in the lungs and enhance their antibacterial effects. Dry powder inhalers (DPIs) are the preferred pulmonary drug delivery system and preparation of an optimum nanoaggregate from nanomicelles by means of spray drying would be valuable. The two-level full factorial design was performed in 16 runs. The effects of carrier type, anti-adhesion agent type, carrier to nanoparticle ratio and anti-adhesion agent to carrier ratio on the size of the microparticles, their in vitro pulmonary deposition, and redispersibility were investigated. Its antibacterial effects against Pseudomonas aeruginosa, Klebsiella pneumoniae, and Streptococcus pneumoniae also were investigated. All independent variables were fitted into two-factorial interaction models. The optimum nanoaggregate was prepared using mannitol and L-phenylalanine with a D_0.5 of 1.7?µm and 60% fine particles. The process had no negative effect on the stability or drug release profile of the nanomicelles. The antibacterial effects of ciprofloxacin against microorganisms increased significantly. This spray drying process could be used for preparation of an optimum DPI from polymeric nanomicelles. This formulation could increase the efficacy of ciprofloxacin for treatment of pulmonary infections.     

乳糖-多柔比星偶联物纳米胶束体内药效学与安全性评价

目的合成乳糖-多柔比星两亲性小分子并制备成纳米胶束,并对其肝癌靶向性和体内抗肿瘤药效及安全性进行评价。方法采用薄膜水化法制备乳糖-多柔比星纳米胶束(lactose-doxorubicin nanomicelles,Lac-DOX NMs),采用动态光散射法测定其粒径,透射电镜观察形态;通过细胞摄取实验考察Lac-DOX NMs对肿瘤细胞的靶向性;CCK-8法测定纳米胶束和游离多柔比星的细胞毒性;构建BALB/c-nu小鼠皮下移植瘤模型,考察Lac-DOX NMs的体内抗肿瘤药效;通过血生化检测,考察该制剂对小鼠肝功能的影响以评价制剂的安全性。结果成功制备了乳糖-多柔比星纳米胶束(Lac-DOX NMs),粒径为(169.2±0.9)nm;细胞摄取实验表明,Lac-DOX NMs对Hu H-7肝癌细胞具有靶向性;细胞毒性实验测得纳米胶束和游离DOX的IC50分别为3.596和2.131μg·mL^-1;药效实验结果显示,Lac-DOX NMs能够显著抑制小鼠移植瘤的增长,Lac-DOX NMs高、低剂量的肿瘤抑制率分别为69.72%和52.40%,均高于DOX裸药(52.27%),P值分别为0.00016和0.94;血生化数据显示,与DOX相比,Lac-DOX NMs肝功能损伤情况显著降低。结论用乳糖修饰多柔比星并将其制成纳米制剂,能够显著提高多柔比星对肝癌细胞的靶向性,增强了抗肿瘤效果,同时降低多柔比星的毒副作用,提高用药安全性。     

空间立构pH敏感喜树碱新型纳米胶束制备及评价#br#

目的 制备空间立构pH敏感喜树碱新型纳米胶束,对其进行质量评价,并考察了胶束的体外抗肿瘤活性。方法 采用透析法制备载喜树碱纳米胶束,响应面法优化其处方工艺,分别用扫描电子显微镜和动态激光散射仪表征其形貌、粒径及粒度分布,采用透析法测定其体外释放行为,并通过细胞活力试验考察其体外抗肿瘤活性。结果 优化得到载药胶束最佳处方工艺为：喜树碱与载体的质量比为26.5:100,搅拌时间为15.5h,透析时间为8h。载药胶束呈球状,粒径(170.4±28.49)nm,PDI为0.236;包封率78.31%,载药量23.55%;体外释放兼具缓释和pH敏感性双重效果。载药胶束和CPT对于Hela细胞的IC50值分别为1.75和4.64μg/mL,而两者对于MCF-7细胞的IC50值分别为5.41和12.78μg/mL。结论 成功制备得到一种新型空间立构pH敏感喜树碱纳米胶束,提高了喜树碱的水溶性及稳定性,并且该胶束具有良好的体外肿瘤抑制效果。     

Amphiphilic dendritic nanomicelle-mediated co-delivery of 5-fluorouracil and doxorubicin for enhanced therapeutic efficacy

Combination cancer therapy has attracted considerable attention due to its enhanced antitumor efficacy and reduced toxicity granted by synergistic effects over monotherapy. The application of nanotechnology is expected to achieve coencapsulation of multiple anticancer agents with enhanced therapeutic efficacy. Herein, a unique nanomicelle based on amphiphilic dendrimer (AmD) consisting of a hydrophilic polyamidoamine dendritic shell and a hydrophobic polylactide core is developed for effectively loading and shuttling 5-fluorouracil (5-Fu) and doxorubicin (Dox). The yielded drug-encapsulated dendritic nanomicelle (5-Fu/Dox-DNM) has a modest average size of 68.6?±?3.3?nm and shows pH-sensitive drug release manner. The parallel activity of 5-Fu and Dox show synergistic anticancer efficacy. The IC₅₀ value of 5-Fu/Dox-DNM toward human breast cancer (MDA-MB-231) cells was 0.25?μg/mL, presenting an 11.2-fold and 6.1-fold increase in cytotoxicity compared to Dox-DNM and 5-Fu-DNM, respectively. Furthermore, 5-Fu/Dox-DNM significantly inhibits the progression of tumor growth in the MDA-MB-231 xenograft tumor mice model. In conclusion, we have demonstrated that our AmD-based combination therapeutic system has promising potential to open an avenue for coencapsulation of multiple chemotherapeutic agents to promote superior anticancer effect.     

盐霉素纳米制剂的研究进展

盐霉素（salinomycin,SAL）作为一种抗生素,已广泛用于畜牧业,近年来研究人员发现该药对多种肿瘤及肿瘤干细胞具有较强的抑制作用,而且体内外研究及早期临床试验结果均表明SAL具有抗肿瘤多重耐药活性,有望成为一种新型的抗肿瘤药物。但是,SAL的水溶性较差,且有一定的毒副作用,为获得更好的治疗效果,SAL制剂学的研究得到药学界的广泛关注。本文对近年来SAL纳米制剂的研究进展进行综述。     

Insight into curcumin nanomicelle‐induced derangements in male reproduction potential: An experimental study

This study was conducted to investigate the possible effects of nanomicelle curcumin (NMC) on spermatogenesis, sperm parameters and in vitro fertilisation potential. For this purpose, 24 mature male Wistar rats were divided into control and test groups. The animals in test groups received 7.5, 15 and 30 mg kg b.w^?1 of NMC (NO = 6 rats in each group). Following 48 days, the DNA integrity of testicular tissues, tubular differentiation (TDI) and spermiogenesis (SPI) indices, sperm parameters and DNA integrity were analysed. Finally, the in vitro fertilisation potential was investigated via evaluating pre‐implantation embryo generation. The NMC diminished the TDI and SPI ratios. The animals in NMC‐received groups exhibited a remarkable (p < .05) reduction in percentage of alive and motile spermatozoa. Moreover, the NMC enhanced the percentage of spermatozoa with decondensed chromatin and elevated the sperm DNA damage ratio. The testicles of NMC‐received groups exhibited severe DNA fragmentation. The percentages of zygote, 2‐cell, blastocysts and hatched embryos generation were decreased in NMC‐received groups compared to control animals. In conclusion, the NMC adversely affects the spermatogenesis and spermiogenesis processes, which in turn results in reducing the sperm quality. Ultimately, decreased sperm quality results in lower pre‐implantation embryo development.