Idris Auni Hamimi, Che Abdullah Che Azurahanim, Yusof Nor Azah, Asmawi Azren Aida, Abdul Rahman Mohd Basyaruddin
Faculty of Chemical and Process Engineering Technology, Universiti Malaysia Pahang, Lebuh Persiaran Tun Khalil Yaakob, Kuantan 26300, Pahang, Malaysia.
Integrated Chemical BioPhysics Research, Faculty of Science, Universiti Putra Malaysia, Serdang 43400, Selangor, Malaysia.
Pharmaceutics. 2023 Apr 22;15(5):1319. doi: 10.3390/pharmaceutics15051319.
Lung cancer is currently the most prevalent cause of cancer mortality due to late diagnosis and lack of curative therapies. Docetaxel (Dtx) is clinically proven as effective, but poor aqueous solubility and non-selective cytotoxicity limit its therapeutic efficacy. In this work, a nanostructured lipid carrier (NLC) loaded with iron oxide nanoparticles (IONP) and Dtx (Dtx-MNLC) was developed as a potential theranostic agent for lung cancer treatment. The amount of IONP and Dtx loaded into the Dtx-MNLC was quantified using Inductively Coupled Plasma Optical Emission Spectroscopy and high-performance liquid chromatography. Dtx-MNLC was then subjected to an assessment of physicochemical characteristics, in vitro drug release, and cytotoxicity. Dtx loading percentage was determined at 3.98% /, and 0.36 mg/mL IONP was loaded into the Dtx-MNLC. The formulation showed a biphasic drug release in a simulated cancer cell microenvironment, where 40% of Dtx was released for the first 6 h, and 80% cumulative release was achieved after 48 h. Dtx-MNLC exhibited higher cytotoxicity to A549 cells than MRC5 in a dose-dependent manner. Furthermore, the toxicity of Dtx-MNLC to MRC5 was lower than the commercial formulation. In conclusion, Dtx-MNLC shows the efficacy to inhibit lung cancer cell growth, yet it reduced toxicity on healthy lung cells and is potentially capable as a theranostic agent for lung cancer treatment.
由于诊断延迟和缺乏治愈性疗法，肺癌目前是癌症死亡的最常见原因。多西他赛（Dtx）在临床上已被证明有效，但水溶性差和非选择性细胞毒性限制了其治疗效果。在这项工作中，开发了一种负载有氧化铁纳米颗粒（IONP）和Dtx的纳米结构脂质载体（NLC，即Dtx-MNLC），作为一种潜在的肺癌治疗诊断剂。使用电感耦合等离子体发射光谱法和高效液相色谱法定量测定了负载到Dtx-MNLC中的IONP和Dtx的量。然后对Dtx-MNLC进行了物理化学特性、体外药物释放和细胞毒性评估。测定Dtx负载率为3.98%，并且将0.36mg/mL的IONP负载到Dtx-MNLC中。该制剂在模拟癌细胞微环境中表现出双相药物释放，其中在最初6小时内释放了40%的Dtx，48小时后实现了80%的累积释放。Dtx-MNLC对A549细胞的细胞毒性高于MRC5细胞，且呈剂量依赖性。此外，Dtx-MNLC对MRC5细胞的毒性低于市售制剂。总之，Dtx-MNLC显示出抑制肺癌细胞生长的功效，同时降低了对健康肺细胞的毒性，并且有潜力作为肺癌治疗的诊断剂。
