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 (IC₅₀ < 1.56 µg/mL) to weakly toxic (IC₅₀ 280.00 µg/mL) and moderately toxic (IC₅₀ = 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.

中文翻译：

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包含吉西他滨和顺铂的雾化含氧制剂对肺癌的治疗：优化，表征和体外评估

吉西他滨（Gem）和顺铂（Cis）目前正用于肺癌治疗，但是它们在高剂量时剧毒。这项研究旨在开发一种含低剂量Gem和Cis（NGC）的脂质体制剂，作为肺癌治疗的替代制剂。NGC是使用非常简单的加热方法制备的，并通过D-最佳混合物设计进行了进一步优化。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，并在27°C保持稳定，长达90天无相分离。气雾剂的产量为96.22％，表明其适合作为气雾剂。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 h的渗透时间内均具有控制释放。进行了针对正常肺（MRC5）和肺癌（A549）细胞系的细胞毒性研究。结果表明，优化后的NGC与毒性极强（IC）的对照（仅Gem + Cis）相比，对MRC5和A549的细胞毒性作用均降低₅₀ h <1.56 µg / mL）至治疗72小时后的中毒性（IC ₅₀ 280.00 µg / mL）和中毒性（IC ₅₀ = 46.00 µg / mL）。这些发现表明，优化的NGC具有极好的潜力，在治疗肺癌的雾化输送系统中具有广阔的前景，值得进一步研究。