Mohamad Saimi Norfatin Izzatie, Salim Norazlinaliza, Ahmad Noraini, Abdulmalek Emilia, Abdul Rahman Mohd Basyaruddin
Integrated Chemical BioPhysics Research, Faculty of Science, Universiti Putra Malaysia, Serdang 43400 UPM, Selangor, Malaysia.
Department of Chemistry, Faculty of Science, Universiti Putra Malaysia, Serdang 43400 UPM, Selangor, Malaysia.
Pharmaceutics. 2021 Jan 5;13(1):59. doi: 10.3390/pharmaceutics13010059.
Gemcitabine (Gem) and cisplatin (Cis) are currently being used for lung cancer treatment, but they are highly toxic in high dosages. This research aimed to develop a niosome formulation containing a low-dosage Gem and Cis (NGC), as an alternative formulation for lung cancer treatment. NGC was prepared using a very simple heating method and was further optimized by D-optimal mixture design. The optimum NGC formulation with particle size, polydispersity index (PDI), and zeta potential of 166.45 nm, 0.16, and -15.28 mV, respectively, was obtained and remained stable at 27 °C with no phase separation for up to 90 days. The aerosol output was 96.22%, which indicates its suitability as aerosolized formulation. An in vitro drug release study using the dialysis bag diffusion technique showed controlled release for both drugs up to 24 h penetration. A cytotoxicity study against normal lung (MRC5) and lung cancer (A549) cell lines was investigated. The results showed that the optimized NGC had reduced cytotoxicity effects against both MRC5 and A549 when compared with the control (Gem + Cis alone) from very toxic (IC < 1.56 µg/mL) to weakly toxic (IC 280.00 µg/mL) and moderately toxic (IC = 46.00 µg/mL), respectively, after 72 h of treatment. These findings revealed that the optimized NGC has excellent potential and is a promising prospect in aerosolized delivery systems to treat lung cancer that warrants further investigation.
吉西他滨（Gem）和顺铂（Cis）目前用于肺癌治疗，但高剂量时毒性很大。本研究旨在开发一种含有低剂量Gem和Cis的脂质体配方（NGC），作为肺癌治疗的替代配方。NGC采用非常简单的加热方法制备，并通过D-最优混合设计进一步优化。获得了最佳的NGC配方，其粒径、多分散指数（PDI）和zeta电位分别为166.45 nm、0.16和 -15.28 mV，在27°C下保持稳定，长达90天无相分离。气雾剂输出率为96.22%，表明其适合作为雾化制剂。使用透析袋扩散技术进行的体外药物释放研究表明，两种药物在长达24小时的渗透过程中均呈现控释。研究了对正常肺（MRC5）和肺癌（A549）细胞系的细胞毒性。结果表明，与对照组（单独使用Gem + Cis）相比，优化后的NGC对MRC5和A549的细胞毒性作用均有所降低，从剧毒（IC < 1.56 µg/mL）分别降至弱毒（IC 280.00 µg/mL）和中度毒性（IC = 46.00 µg/mL），在治疗72小时后。这些发现表明，优化后的NGC具有优异的潜力，在雾化给药系统治疗肺癌方面具有广阔前景，值得进一步研究。
