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水飞蓟宾载聚己内酯/泊洛沙姆 F68 可吸入纳米粒对肺癌的靶向效率:体外与体内研究。

Lung cancer targeting efficiency of Silibinin loaded Poly Caprolactone /Pluronic F68 Inhalable nanoparticles: In vitro and In vivo study.

机构信息

Department of Pharmaceutical Sciences, Saurashtra University, Rajkot, Gujarat, India.

Department of Pharmaceutical Sciences, Sardar Patel University, Vallabh Vidyanagar, Gujarat, India.

出版信息

PLoS One. 2022 May 13;17(5):e0267257. doi: 10.1371/journal.pone.0267257. eCollection 2022.

Abstract

Silibinin (SB) is shown to have an anticancer properties. However, its clinical therapeutic effects have been restricted due to its low water solubility and poor absorption after oral administration. The aim of this study was to develop SB-loaded PCL/Pluronic F68 nanoparticles for pulmonary delivery in the treatment of lung cancer. A modified solvent displacement process was used to make nanoparticles, which were then lyophilized to make inhalation powder, Nanoparticles were characterized with DSC, FTIR,SEM and In vitro release study. Further, a validated HPLC method was developed to investigate the Biodistribution study, pharmacokinetic parameters. Poly Caprolactone PCL / Pluronic F68 NPs showed the sustained release effect up to 48 h with an emitted (Mass median Aerodynamic diameter)MMAD and (Geometric size distribution)GSD were found to be 4.235 ±0.124 and 1.958±1.23 respectively. More specifically, the SB Loaded PCL/Pluronic F 68 NPs demonstrated long circulation and successful lung tumor-targeting potential due to their cancer-targeting capabilities. SB Loaded PCL/Pluronic F68 NPs significantly inhibited tumour growth in lung cancer-induced rats after inhalable administration. In a pharmacokinetics study, PCL/ Pluronic F68 NPs substantially improved SB bioavailability, with a more than 4-fold rise in AUC when compared to IV administration. These findings indicate that SB-loaded PCL/PluronicF68 nanoparticles may be a successful lung cancer therapy delivery system.

摘要

水飞蓟宾(SB)被证明具有抗癌特性。然而,由于其在水中的低溶解度和口服后吸收不良,其临床治疗效果受到限制。本研究旨在开发载 SB 的 PCL/Pluronic F68 纳米粒用于治疗肺癌的肺部给药。采用改良的溶剂置换法制备纳米粒,然后冷冻干燥制成吸入粉末。对纳米粒进行 DSC、FTIR、SEM 和体外释放研究。此外,还建立了一种经验证的 HPLC 方法来研究生物分布研究和药代动力学参数。PCL/Pluronic F68 NPs 表现出长达 48 小时的持续释放效果,发射(质量中值空气动力学直径)MMAD 和(几何尺寸分布)GSD 分别为 4.235±0.124 和 1.958±1.23。更具体地说,由于其癌症靶向能力,载 SB 的 PCL/Pluronic F68 NPs 表现出长循环和成功的肺肿瘤靶向潜力。在可吸入给药后,载 SB 的 PCL/Pluronic F68 NPs 显著抑制了肺癌诱导大鼠的肿瘤生长。在药代动力学研究中,与 IV 给药相比,PCL/Pluronic F68 NPs 显著提高了 SB 的生物利用度,AUC 增加了 4 倍以上。这些发现表明,载 SB 的 PCL/Pluronic F68 纳米粒可能是一种成功的肺癌治疗药物传递系统。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/784d/9106168/6ee5f160e0b0/pone.0267257.g001.jpg

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