OPTIMIZATION AND IN VITRO EVALUATION OF 5-FLUOROURACIL – LOADED LONG – CIRCULATING LIPOSOMES
MARCELA ACHIM1, IOAN TOMUȚĂ1*, DANA MUNTEAN1, ALINA PORFIRE1, LUCIA RUXANDRA TEFAS1, LAURA PATRAS2,3, EMILIA LICARETE2,3, MARIUS COSTEL ALUPEI2,3, LAURIAN VLASE1, MANUELA BANCIU2,3
1.Department of Pharmaceutical Technology and Biopharmacy, Faculty of Pharmacy, “Iuliu Hațieganu” University of Medicine and Pharmacy, 41 Victor Babeș Street, 400012 Cluj-Napoca, Romania
2.Department of Molecular Biology and Biotechnology, Faculty of Biology and Geology, “Babeș-Bolyai” University, 400006, Cluj-Napoca, Romania
3.Molecular Biology Centre, Institute for Interdisciplinary Research in Bio-Nano-Sciences, “Babeș-Bolyai” University, 400271, Cluj-Napoca, Romania
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5-Fluorouracil (5-FU) is an anticancer drug widely used in the treatment of colorectal cancers. In this work, long-circulating liposomes (LCL) were proposed as carriers able to improve the therapy with 5-FU. The objective was to optimize the formulation of 5-FU-loaded long circulating liposomes (LCL-5-FU) using the method of experimental design and to evaluate the in vitro drug release and cytotoxicity on C26 murine colon carcinoma cells cultivated in monoculture as well as in co-culture with murine peritoneal macrophages. The influence of phospholipids concentration and phospholipids to cholesterol molar ratio was studied on 5-FU liposomal concentration, entrapment efficiency and liposomes’ size. The optimized formulation (LCL-5-FU-OPT) had liposomal 5-FU concentration of 331.4 µg/mL, entrapment efficiency of 3.18 % and liposomes’ size of 200 nm. The in vitro release test has shown a diffusion of 5-FU of 90% in 3 hours. The cytotoxicity data indicated that LCL-5-FU-OPT exerted strong and similar inhibitory effects on the proliferation of C26 tumour cells under both culture conditions as those exerted by free 5-FU administration. In conclusion, the liposomal 5-FU formulation optimized within our studies might offer promise for future anti-cancer therapies based on passive tumour targeting by using LCL.