Polycaprolactone – Vitamin E TPGS micelles for delivery of paclitaxel: In vitro and in vivo evaluation

IF 5.2 2区 医学 Q1 PHARMACOLOGY & PHARMACY International Journal of Pharmaceutics: X Pub Date : 2024-05-03 DOI:10.1016/j.ijpx.2024.100253
Ziyad Binkhathlan , Osman Yusuf , Raisuddin Ali , Abdullah H. Alomrani , Aws Alshamsan , Abdullah K. Alshememry , Aliyah Almomen , Musaed Alkholief , Ibrahim A. Aljuffali , Faleh Alqahtani , Saad Alobid , Essam A. Ali , Afsaneh Lavasanifar
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Abstract

This study aimed to present findings on a paclitaxel (PTX)-loaded polymeric micellar formulation based on polycaprolactone-vitamin E TPGS (PCL-TPGS) and evaluate its in vitro anticancer activity as well as its in vivo pharmacokinetic profile in healthy mice in comparison to a marketed formulation. Micelles were prepared by a co-solvent evaporation method. The micelle's average diameter and polydispersity were determined using dynamic light scattering (DLS) technique. Drug encapsulation efficiency was assessed using an HPLC assay. The in vitro cytotoxicity was performed on human breast cancer cells (MCF-7 and MDA-MB-231) using MTT assay. The in vivo pharmacokinetic profile was characterized following a single intravenous dose of 4 mg/kg to healthy mice. The mean diameters of the prepared micelles were ≤ 100 nm. Moreover, these micelles increased the aqueous solubility of PTX from ∼0.3 μg/mL to reach nearly 1 mg/mL. While the PTX-loaded micelles showed an in vitro cytotoxicity comparable to the marketed formulation (Ebetaxel), drug-free PCL-TPGS micelles did not show any cytotoxic effects on both types of breast cancer cells (∼100% viability). Pharmacokinetics of PTX as part of PCL-TPGS showed a significant increase in its volume of distribution compared to PTX conventional formulation, Ebetaxel, which is in line with what was reported for clinical nano formulations of PTX, i.e., Abraxane, Genexol-PM, or Apealea. The findings of our studies indicate a significant potential for PCL-TPGS micelles to act as an effective system for solubilization and delivery of PTX.

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用于输送紫杉醇的聚己内酯-维生素 E TPGS 胶束:体外和体内评估
本研究旨在介绍一种基于聚己内酯-维生素 E TPGS(PCL-TPGS)的紫杉醇(PTX)负载聚合物胶束制剂的研究结果,并评估其体外抗癌活性及其在健康小鼠体内的药代动力学特征,并与市场上销售的制剂进行比较。胶束采用共溶剂蒸发法制备。使用动态光散射(DLS)技术测定了胶束的平均直径和多分散性。采用 HPLC 分析法评估药物的封装效率。采用 MTT 法对人乳腺癌细胞(MCF-7 和 MDA-MB-231)进行体外细胞毒性测试。对健康小鼠单次静脉注射 4 mg/kg 剂量后,对其体内药代动力学特征进行了研究。制备的胶束平均直径≤ 100 nm。此外,这些胶束还提高了 PTX 的水溶性,使其从 0.3 μg/mL 提高到接近 1 mg/mL。虽然负载 PTX 的胶束在体外显示出与市售制剂(Ebetaxel)相当的细胞毒性,但不含药物的 PCL-TPGS 胶束对两种类型的乳腺癌细胞均未显示出任何细胞毒性作用(存活率为 100%)。与 PTX 传统制剂 Ebetaxel 相比,作为 PCL-TPGS 一部分的 PTX 的药代动力学显示其分布容积显著增加,这与 PTX 的临床纳米制剂(即 Abraxane、Genexol-PM 或 Apealea)的报道一致。我们的研究结果表明,PCL-TPGS 胶束作为一种有效的 PTX 增溶和递送系统具有巨大的潜力。
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来源期刊
International Journal of Pharmaceutics: X
International Journal of Pharmaceutics: X Pharmacology, Toxicology and Pharmaceutics-Pharmaceutical Science
CiteScore
6.60
自引率
0.00%
发文量
32
审稿时长
24 days
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