Objective: This study aims to create a new delivery system for pemetrexed, employing a metal-C60 fullerene combination for the first time. Additionally, a lung cancer cell line study will be used to examine the impact of this combination on the release, behavior, and drug’s cytotoxicity. Methods: To utilize a laser to irradiate hydrocarbons, fullerene C60 (Buckysomes) was produced and then nanosized by adding different volumes of isopropyl alcohol and ultrasonication. Gold Nanoparticles (AuNPs) and nickel nanoparticles (NiNPs) were also prepared each one separately and added to the previous mixture together with Pemetrexed (PMX) with further ultrasonication for 20 minutes. The mixture is kept in the refrigerator for 20 hours and then filtered. The precipitate was dried and characterized for particle size, invitro release, and anticancer activity in comparison to pemetrexed loaded on C60 fullerene previously prepared in our laboratory. Results: The evaluation techniques revealed the successful loading of pemetrexed on metals- fullerene C60 nanocarrier, SG10 was the optimum sample with % of yield reach to 95.36. The release profile shows that the percentage release of pemetrexed after 240 minutes is equal to 40% from pure PMX, while the release after 240 minute was found to be 87.8 % from pemetrexed loaded gold nanoparticles (AuNPs) fullerene C60 nanocarrier (SG10), while NiNPs not significantly improved the release profile of Pemetrexed from Pemetrexed loaded NiNPs – fullerene (SN7). Pemetrexed loaded on gold nanoparticles (AuNPs), when compared to pure PMX (3.1 M) and SN7 (11.5 M), fullerene nanocarrier (SG10) exhibits a lower IC50 (1.55 M) and a greater cytotoxic effect (high IR percent) on A549 cancer cells. Pemetrexed’s cytotoxicity in A549 was enhanced after being loaded onto gold nanoparticles (AuNPs)-fullerene nanocarriers (90.4% cell death for SG10) as opposed to pure drug (60% cell death). This finding suggests that the loading process enhanced the drug’s cytotoxic activity for the tumor cells, which may have sped up the onset of action (30% cell death after 24 hours). Conclusion: This study successfully prepared Metals- fullerene C60 Buckysomes loaded with pemetrexed utilizing gold and nickel, which may serve (especially Au- fullerene) as a suitable nanocarrier for pemetrexed, resulting in an improvement to solubility, the release pattern, and cytotoxicity.
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