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21.
Zhepeng Liu Haini Chen Fengmei Lv Jun Wang Shoujin Zhao Yijun Li Xuexin Xue Yu Liu Gang Wei Weiyue Lu 《International journal of molecular sciences》2021,22(16)
To optimize the anti-tumor efficacy of combination therapy with paclitaxel (PTX) and imatinib (IMN), we used coaxial electrospray to prepare sequential-release core–shell microparticles composed of a PTX-loaded sodium hyaluronate outer layer and an IMN-loaded PLGA core. The morphology, size distribution, drug loading, differential scanning calorimetry (DSC), Fourier transform infrared spectra (FTIR), in vitro release, PLGA degradation, cellular growth inhibition, in vivo vaginal retention, anti-tumor efficacy, and local irritation in a murine orthotopic cervicovaginal tumor model after vaginal administration were characterized. The results show that such core–shell microparticles were of spherical appearance, with an average size of 14.65 μm and a significant drug-loading ratio (2.36% for PTX, 19.5% for IMN, w/w), which might benefit cytotoxicity against cervical-cancer-related TC-1 cells. The DSC curves indicate changes in the phase state of PTX and IMN after encapsulation in microparticles. The FTIR spectra show that drug and excipients are compatible with each other. The release profiles show sequential characteristics in that PTX was almost completely released in 1 h and IMN was continuously released for 7 days. These core–shell microparticles showed synergistic inhibition in the growth of TC-1 cells. Such microparticles exhibited prolonged intravaginal residence, a >90% tumor inhibitory rate, and minimal mucosal irritation after intravaginal administration. All results suggest that such microparticles potentially provide a non-invasive local chemotherapeutic delivery system for the treatment of cervical cancer by the sequential release of PTX and IMN. 相似文献
22.
Misara Hamoudeh Roudayna Diab Hatem Fessi Charles Dumontet Delphine Cuchet 《Drug development and industrial pharmacy》2013,39(7):698-707
In our pursuit to develop suitable therapeutic particulate systems for intratumoral delivery by the targeted multi-therapy (TMT) technique, we describe the preparation of paclitaxel-loaded poly(d,l-lactic-co-glycolic) acid (PLGA) microparticles (MPs) (drug loading 35–38%, wt/wt; size 0.7–5 μm). Magnetite (15%, wt/wt) was also incorporated in some preparations for a future magnetic resonance imaging (MRI)-guided delivery. X-ray diffraction (XRD) and differential scanning calorimetry (DSC) experiments showed that paclitaxel was not encapsulated in its initial crystalline form. The paclitaxel in vitro release pattern showed a biphasic tendency with a burst effect followed by a sustained release (28% released amount after 1 month), which was accompanied with MP erosion and degradation signs as confirmed by scanning electronic microscopy (SEM) micrographs. The paclitaxel-loaded MPs demonstrated a dose-dependent antitumor effect on human uterine cancer cells, with an IC50 value relatively close to that of commercial Taxol®. This paclitaxel delivery system represents a potent antiprofilerative and radiosensitizer agent for intratumoral administration via the TMT technique. 相似文献
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紫杉醇聚合物胶束载药体系的研究进展 总被引:1,自引:0,他引:1
紫杉醇(paclitaxel,PTX)是一种常用的抗肿瘤药物,但其极差的水溶性限制了其在临床上的应用。为使其能更好的为人体所利用,近年来,研究者们开发了多种紫杉醇载药体系,其中聚合物胶束载药体系以其特有的优点为目前研究的热点,并具有广阔的发展前景。介绍了近年来采用两亲嵌段共聚物制备紫杉醇聚合物给药体系的研究进展。展望了该体系今后的发展方向。 相似文献
25.
Lin CL Chen RF Chen JY Chu YC Wang HM Chou HL Chang WC Fong Y Chang WT Wu CY Chiu CC 《International journal of molecular sciences》2012,13(5):6236-6245
Caffeic acid (CA), a natural phenolic compound, is abundant in medicinal plants. CA possesses multiple biological effects such as anti-bacterial and anti-cancer growth. CA was also reported to induce fore stomach and kidney tumors in a mouse model. Here we used two human lung cancer cell lines, A549 and H1299, to clarify the role of CA in cancer cell proliferation. The growth assay showed that CA moderately promoted the proliferation of the lung cancer cells. Furthermore, pre-treatment of CA rescues the proliferation inhibition induced by a sub-IC(50) dose of paclitaxel (PTX), an anticancer drug. Western blot showed that CA up-regulated the pro-survival proteins survivin and Bcl-2, the down-stream targets of NF-κB. This is consistent with the observation that CA induced nuclear translocation of NF-κB p65. Our study suggested that the pro-survival effect of CA on PTX-treated lung cancer cells is mediated through a NF-κB signaling pathway. This may provide mechanistic insights into the chemoresistance of cancer calls. 相似文献
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The selection of pharmaceutical polymorphisms in the final production step is very important in terms of product recovery, properties, and storage. The amorphous, dihydrated crystalline, and anhydrous crystalline forms of paclitaxel were prepared using precipitation, spray drying, and colloid formation methods. These methods were found to be highly efficient and convenient, giving high recovery, short processing time, and good stability, as compared with conventional methods such as freeze drying, evaporation, recrystallization, and melting. The polymorphic natures of the resulting paclitaxel samples were confirmed by XRPD, IR, TGA, DSC, and SEM. The dissolution rates of the paclitaxel samples were studied in pharmaceutical solvents, which included cotton seed oil, corn oil, tricaprylin, and tributyrin. For each solvent, all of the amorphous paclitaxel samples showed much higher dissolution rates than the dihydrated crystalline, anhydrous crystalline, and commercial forms, and can be used for clinical applications that demand improvements in drug delivery. 相似文献
28.
Ping Ouyang Yun-qing Kang Guang-fu Yin Zhong-bing Huang Ya-dong Yao Xiao-ming Liao 《Frontiers of Materials Science in China》2009,3(1):15-24
In this work, chemically bonded poly(D, L-lactide)-polyethylene glycol-poly(D, L-lactide) (PLA-PEG-PLA) triblock copolymers
with various PEG contents and PLA homopolymer were synthesized via melt polymerization, and were confirmed by FTIR and 1H-NMR results. The molecular weight and polydispersity of the synthesized PLA and PLA-PEG-PLA copolymers were investigated
by gel permeation chromatography. Hydrophilicity of the copolymers was identified by contact angle measurement. PLA-PEG-PLA
and PLA microparticles loaded with and without PTX were then produced via solution enhanced dispersion by supercritical CO2 (SEDS) process. The effect of the PEG content on the particle size distribution, morphology, drug load, and encapsulation
efficiency of the fabricated microparticles was also studied. Results indicate that PLA and PLA-PEG-PLA microparticles all
exhibit sphere-like shape with smooth surface, when PEG content is relatively low. The produced microparticles have narrow
particle size distributions and small particle sizes. The drug load and encapsulation efficiency of the produced microparticles
decreases with higher PEG content in the copolymer matrix. Moreover, high hydrophilicity is found when PEG is chemically attached
to originally hydrophobic PLA, providing the produced drug-loaded microparticles with high hydrophilicity, biocompatibility,
and prolonged circulation time, which are considered of vital importance for vessel-circulating drug delivery system. 相似文献
29.
125I标记紫杉醇的方法 总被引:1,自引:0,他引:1
摘要:采用改良的氯胺T法,先用稳定的NaI与紫杉醇作用,再以放射性Na125I标记紫杉醇(paclitaxel),建立了125I标记紫杉醇的方法。采用纸层析及HPLC测定标记产物的标记率、纯化后放射化学纯度,采用纸层析测定标记产物在不同温度、储存溶剂条件下的体外稳定性,红外光谱鉴定产物。改良Ch-T法所得标记产物的标记率与硝酸氧化法和传统氯胺T法相比较。结果显示,采用改良氯胺T法标记率约63.1%±5.7%,放射化学纯度约96.3%±1.3%;标记物储存于4℃生理盐水或乙醇储存体系中24h、120h,放化纯度分别>95%和约90%;在血浆中稳定性也较好,在4℃ 、37℃放置24h,放化纯度分别为92.3%±0.4%、89.5%±0.6% 。以上结果表明,改良氯胺T法标记紫杉醇方法简便,标记率高,标记产物稳定性较好,能够满足放射性示踪实验的要求。 相似文献
30.
透析法制备紫杉醇聚合物胶束给药系统 总被引:6,自引:0,他引:6
以4-二甲氨基吡啶(DMAP)和二环己基碳二亚胺(DCC)作催化剂和缩合剂,合成聚乙二醇-共轭亚油酸(PEG-CLA)聚合物;以PEG-CLA为载体,采用透析法制备了紫杉醇聚合物胶束给药系统;利用动态光散射法(DLS)、透射电镜(TEM)、X-射线光电能谱(XPS)表征了紫杉醇胶束的粒径与粒径分布、形貌以及表面组分特性,分别在pH值为7.4的磷酸盐缓冲溶液(PBS)和1 mol/L水杨酸钠溶液中进行了紫杉醇胶束的体外药物释放试验。研究结果表明,所制备的紫杉醇胶束外形大致呈球状,粒径在100 nm左右,且粒径分布较窄。X-射线光电能谱显示,胶束表面没有吸附紫杉醇。在体外药物释放实验中,发现水杨酸钠对紫杉醇的释放起促进作用。 相似文献