Pectin, a naturally occurring biopolymer has been found to have increasing applications in the pharmaceutical and biotechnology industry. Sugars with their three-dimensional structures are important for many biological functions. We report preparation of negatively charged pectin nanoparticles encapsulating paclitaxel, a broad-spectrum anticancer drug for possible therapeutic applications. The mean diameter of the nanoparticles was ~300–350 nm with an encapsulation efficiency ~17 %. The TEM studies indicated that the particles were spherical in shape and their sizes are in unison with the DLS size spectra. The surface charge of pectin polymer was −5 mV and of nanoparticles were ~ −32 mV. The enhanced surface charge shows greater stability. The high electrophoretic mobility of ~3.5 to 1.5 μmcm/Vs confirmed the nano-size of particles. We compared the cytotoxic effect of paclitaxel (Pax) per se, pectin nanoparticles (PPN), and pectin chains on Hep G2, hepatic carcinoma cell line. Dose-dependent cytotoxicity was observed, wherein ~21.7 ± 3.2 % cytotoxicity was observed by PPN, but Pax per se showed ~55.6 ± 3.5 % cytotoxicity in a 72-h assay. The pharmacokinetics and biodistribution studies on Balb/c mice indicated that the nanoparticles had prolonged plasma retention of the drug with major accumulation in liver tissue after an i.v. tail vein injection of 20 mg/kg drug. The rank order of concentration are as follows, i.e., liver > kidney > lung > spleen for the PPN and spleen > liver > kidney ≥ lung for Pax per se. The in vitro studies clearly indicated that the efficacy of the drug was not compromised by encapsulation, making it a good candidate to deliver biopharmaceuticals. Nanoparticles produced free radicals in the free cell system and this ability caused oxidative stress, which may give rise to inflammation, cell destruction, and genotoxicity. Thus, the results obtained in this study holds great promise for pectin nanoparticles to be exploited for passive delivery of paclitaxel to tumor tissues, in particular, liver cancers.

中文翻译：

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带紫杉醇的带负电荷的果胶纳米颗粒的药代动力学和生物分布。

果胶是一种天然存在的生物聚合物，已发现在制药和生物技术行业中的应用越来越广泛。具有三维结构的糖对于许多生物学功能都很重要。我们报告了包封紫杉醇的负电荷果胶纳米颗粒的制备，紫杉醇是一种广谱抗癌药物，可能用于治疗用途。纳米粒子的平均直径为〜300–350 nm，封装效率为〜17％。TEM研究表明，颗粒为球形，其尺寸与DLS尺寸光谱一致。果胶聚合物的表面电荷为-5 mV，纳米颗粒的表面电荷为〜-32 mV。增强的表面电荷显示出更高的稳定性。〜3.5至1.5μmcm/ Vs的高电泳迁移率证实了颗粒的纳米尺寸。我们比较了紫杉醇（Pax）本身，果胶纳米颗粒（PPN）和果胶链对Hep G2，肝癌细胞系的细胞毒性作用。观察到剂量依赖性的细胞毒性，其中通过PPN观察到〜21.7±3.2％的细胞毒性，但是Pax本身在72小时的试验中显示出〜55.6±3.5％的细胞毒性。对Balb / c小鼠的药代动力学和生物分布研究表明，在静脉内注射20 mg / kg药物后，纳米颗粒延长了药物的血浆保留时间，并在肝脏组织中大量积累。浓度的等级顺序如下，即对于PPN而言，肝脏>肾脏>肺>脾脏，对于Pax而言，脾脏>肝脏>肾脏>肺≥Pax本身。体外研究清楚地表明，该药物的功效不受封装的影响，使其成为提供生物药品的理想人选。纳米粒子在自由细胞系统中产生自由基，这种能力引起氧化应激，这可能引起炎症，细胞破坏和基因毒性。因此，在这项研究中获得的结果为将果胶纳米颗粒用于将紫杉醇被动递送至肿瘤组织（特别是肝癌）具有广阔的前景。