肺癌在临床实践中是一个具有转移性和对传统治疗方法有抗药性的严峻挑战。抗癌药物的联合输送为克服抗药性、最小化系统毒性提供了潜在的解决方案。将这些药物装载到纳米结构的脂质载体(NLCs)内提供了一种增强淋巴输送、降低复发风险的有希望的策略。本研究旨在开发一种装有吉非替尼和阿扎胞苷（GEF-AZT-NLC）的NLC配方，用于治疗转移性抗药性肺癌。对配方的理化特性进行了表征，并使用透析袋法评估了体外药物释放情况。在肺癌细胞系上评估了GEF-AZT-NLC配方的细胞毒性活性，并使用悬浮红细胞评估了其血液相容性。制备的配方显示出纳米尺度大小（235-272 nm）和负Zeta电位值（-15到-31 mV）。体外研究结果表明，GEF-AZT-NLC配方在实验结束时保留了超过20%的GEF和60%的AZT。血液相容性研究证明了该配方在治疗用途上的安全性，而细胞毒性研究则表明将两种抗癌药物封装在NLCs中可能对治疗抗药性癌细胞有优势。总之，本研究开发的GEF-AZT-NLC配方有望成为治疗转移性抗药性肺癌的潜在治疗工具。

Lung cancer is a formidable challenge in clinical practice owing to its metastatic nature and resistance to conventional treatments. The codelivery of anticancer agents offers a potential solution to overcome resistance and minimize systemic toxicity. The encapsulation of these agents within nanostructured lipid carriers (NLCs) provides a promising strategy to enhance lymphatic delivery and reduce the risk of relapse. This study aimed to develop an NLC formulation loaded with Gefitinib and Azacitidine (GEF-AZT-NLC) for the treatment of metastatic-resistant lung cancer. The physicochemical properties of the formulations were characterized, and in vitro drug release was evaluated using the dialysis bag method. The cytotoxic activity of the GEF-AZT-NLC formulations was assessed on a lung cancer cell line, and hemocompatibility was evaluated using suspended red blood cells. The prepared formulations exhibited nanoscale size (235-272 nm) and negative zeta potential values (-15 to -31 mV). In vitro study revealed that the GEF-AZT-NLC formulation retained more than 20% and 60% of GEF and AZT, respectively, at the end of the experiment. Hemocompatibility study demonstrated the safety of the formulation for therapeutic use, while cytotoxicity studies suggested that the encapsulation of both anticancer agents within NLCs could be advantageous in treating resistant cancer cells. In conclusion, the GEF-AZT-NLC formulation developed in this study holds promise as a potential therapeutic tool for treating metastatic-resistant lung cancer.