Ajdari Mohammadreza, Ranjbar Aliyeh, Karimian Khashayar, Karimi Maryam, Heli Hossein, Sattarahmady Naghmeh
Nanomedicine and Nanobiology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
Arasto Pharmaceutical Chemicals Inc., Yousefabad, Jahanarar Avenue, Tehran, Iran.
J Biomed Phys Eng. 2024 Apr 1;14(2):159-168. doi: 10.31661/jbpe.v0i0.2401-1708. eCollection 2024 Apr.
Docetaxel (DXL) is an antineoplastic agent for cancer treatment, the therapeutic efficiency of which is limited due to low solubility, hydrophobicity, and tissue specificity.
In this study, nano-niosomes were introduced for improving therapeutic index of DXL.
In this experimental study, two nano-niosomes were synthesized using Span 20® and Span 80® and a thin film hydration method with DXL loading (DXL-Span20 and DXL-Span80). Characterization, in-vitro cytotoxicity and bioavailability of the nano-niosomes was also evaluated via in-vivo experiments.
DXL-Span20 and DXL-Span80 have vesicles size in a range of 84-90 nm and negative zeta potentials. DXL entrapment efficiencies were obtained as 69.6 and 74.0% for DXL-Span20 and DXL-Span80, respectively; with an in-vitro sustained release patterns. Cytotoxicity assays were performed against MDA-MB-231, Calu-6, and AsPC-1 cell lines, and the results indicated that DXL loading into nano-niosomes led to decrement in values of half-maximal inhibitory concentration (IC50) at least 2.5 times and at most 6.5 times, compared to free DXL. Moreover, the rat blood bioavailability of DXL after intraperitoneal administration and the pharmacokinetic parameters indicated higher DXL plasma level and the higher effectiveness of DXL-Span80 compared to DXL-Span20.
Carrying DXL by the nano-niosomes led to enhanced cytotoxicity (and lower IC50 values) and higher efficacy with enhanced pharmacokinetic parameters.
多西他赛（DXL）是一种用于癌症治疗的抗肿瘤药物，由于其低溶解度、疏水性和组织特异性，其治疗效果有限。
本研究引入纳米囊泡以提高多西他赛的治疗指数。
在本实验研究中，使用司盘20®和司盘80®通过薄膜水化法合成了两种负载多西他赛的纳米囊泡（DXL-司盘20和DXL-司盘80）。还通过体内实验评估了纳米囊泡的表征、体外细胞毒性和生物利用度。
DXL-司盘20和DXL-司盘80的囊泡大小在84-90nm范围内，zeta电位为负。DXL-司盘20和DXL-司盘80的包封率分别为69.6%和74.0%，具有体外缓释模式。对MDA-MB-231、Calu-6和AsPC-1细胞系进行了细胞毒性试验，结果表明，与游离多西他赛相比，将多西他赛负载到纳米囊泡中导致半数抑制浓度（IC50）值至少降低2.5倍，最多降低6.5倍。此外，腹腔注射后多西他赛在大鼠体内的血药生物利用度和药代动力学参数表明，与DXL-司盘20相比，DXL-司盘80的多西他赛血浆水平更高，疗效更高。
纳米囊泡携带多西他赛可增强细胞毒性（降低IC50值），提高疗效，并改善药代动力学参数。
