(T1230-05-30) Enhanced Codelivery of Gefitinib and Azacitidine for Treatment of Metastatic-Resistant Lung Cancer Using Biodegradable Lipid Nanoparticles

Purpose: Lung cancer is a serious and widespread problem, posing a significant challenge in the clinical setting due to treatment resistance and metastasis. Co-delivering anticancer agents can decrease systemic toxicity and overcome resistance, while encapsulating these agents within lipid nanoparticles can enhance lymphatic delivery and decrease the risk of relapse. This study aimed to prepare a nanostructured lipid carrier (NLC) formulation loaded with gefitinib and azacitidine (GEF-AZT-NLC) to treat metastatic-resistant lung cancer.

Methods: The physicochemical properties of the formulations were characterized, and in-vitro drug release was assessed using the dialysis bag method. The cytotoxic activity of the GEF-AZT-NLC formulations was evaluated using a lung cancer cell line, and the hemocompatibility of the formulations was assessed using suspended red blood cells.

Results: The prepared formulations were found to be within the nanosize range (235-272 nm) and had a negative zeta potential value (-15 to -31 mV). In-vitro studies showed that the prepared GEF-AZT-NLC formulation retained more than 20% and 60% of GEF and AZT, respectively, at the end of the experiment. Hemocompatibility studies demonstrated that the formulation was safe for therapeutic use, and cytotoxicity studies revealed that encapsulating both anticancer agents in NLC could be beneficial in treating resistant cancer cells.

Conclusion: In conclusion, the prepared GEF-AZT-NLC formulation shows promise as a tool for treating metastatic-resistant lung cancer.

Acknowledgements: The authors extend their appreciation to the Deputyship for Research & Innovation, Ministry of Education in Saudi Arabia for funding this work

Composition of the prepared NLC formulations

In-vitro release from the prepared NLC formulations A) GEF, and B) AZT. Data were expressed as the mean ± SD, N=3.

IC 50 of GEF, GEF-NLC, AZT, AZT-NLC, GEF + AZT, and GEF-AZT-NLC following 24 h incubation time with lung cancer cell line. Data were expressed as mean ± SD, N= 3, p-value significant at *0.05, **0.01, and ***0.001.