Fisetin-loaded nanocochleates: formulation, characterisation, in vitro anticancer testing, bioavailability and biodistribution study
Fisetin-loaded nanocochleates: formulation, characterisation, in vitro anticancer testing, bioavailability and biodistribution study
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DOI：
10.1517/17425247.2013.860131
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发表时间：
2014-01-01
影响因子：
6.6
通讯作者：
Thorat, Uday H.
中科院分区：
文献类型：
--
作者：
Bothiraja, Chellampillai;Yojana, Bhagwat D.;Thorat, Uday H.
背景资料：天然类黄酮非瑟酮已显示出抗癌特性，但由于其水溶性差和体内代谢广泛，其体内给药仍具有挑战性。这一关头需要一个有效的，控制释放和安全的制剂非瑟酮将是一个显着的进步，用于治疗cancer.Objectives：Nanocleates是独特的脂质为基础的超分子组装体组成的带负电荷的磷脂和二价阳离子。目的是开发和评估非瑟酮纳米脂质卷，以提高其治疗效果。使用的捕获方法，非瑟酮加载二肉豆蔻酰磷脂酰胆碱脂质体囊泡转化为nanocleyates的行动的Ca 2+离子。这些nanocookeates进一步评估的理化，在体外抗癌和溶血，药代动力学和组织分布study.Results：稳定的卷起层，以及纳米脂质卷具有粒径和包封率（EE）分别为275 ± 4 nm和84.31 +/-2.52%，获得细长的结构。纳米脂质卷表现出的安全性和持续释放的非瑟酮在生理pH值。观察到对人乳腺癌MCF-7细胞的体外抗癌1.3倍的改善。在小鼠中的药代动力学研究显示，腹腔内注射的纳米脂质卷显示出141倍的相对生物利用度。结论：研制的纳米脂质卷显著提高了非瑟酮的抗肿瘤疗效、生物利用度和安全性。nanocoolates技术将有助于管理这种黄酮类化合物在clinical setting.Areas covered：在这篇研究文章中，我们专注于基于脂质的超分子组装“nanocoolates”组成的带负电荷的磷脂和二价阳离子作为药物载体的全身给药系统，并讨论了他们的配方，优化，表征，在体外和体内的性能。
Background: The natural flavonoid fisetin has shown anticancer properties but its in vivo administration remains challenging due its poor aqueous solubility and extensive in vivo metabolism. This juncture demands an effective, controlled release and safe formulation of fisetin would be a significant advance for the treatment of cancer.Objectives: Nanocochleates are unique lipid-based supramolecular assemblies composed of a negatively charged phospholipid and a divalent cation. The aim was to develop and evaluate fisetin-loaded nanocochleates to improve its therapeutic efficacy. Using the trapping method, fisetin-loaded dimyristoylphosphatidylcholine liposomal vesicles were converted into nanocochleates by the action of Ca2+ ions. These nanocochleates were further evaluated for physicochemical, in vitro anticancer and haemolysis, pharmacokinetics and tissue distribution study in mice.Results: Stable rolled-up layers as well as elongated structure of nanocochleates possessing particle size and encapsulation efficiency (EE) of 275 + 4 nm and 84.31 +/- 2.52%, respectively were obtained. Nanocochleates demonstrated safety and a sustained release of fisetin at physiological pH. A 1.3-fold improvement in vitro anticancer towards human breast cancer MCF-7 cells was observed. Pharmacokinetics studies in mice revealed that nanocochleates injected intraperitonially showed a 141-fold higher relative bioavailability. Moreover, a low tissue distribution was observed.Conclusion: Developed nanocochleates markedly improved anticancer efficacy, bioavailability and safety of fisetin. The nanocochleates technology would facilitate the administration of this flavonoid in the clinical setting.Areas covered: In this research article, we focused on lipid-based supramolecular assembly 'nanocochleates' composed of negatively charged phospholipids and divalent cation as drug carrier for systemic delivery system and discussed their formulations, optimisation, characterization, in vitro and in vivo performance.