Development of 5-fluorouracil-loaded nano-sized liposomal formulation by two methods: Strategies to enhance encapsulation efficiency of hydrophilic drugs

Abstract

The number of studies conducted with liposomes to reduce side effects in systemic administration of chemotherapeutic agents is increasing day by day. One of these chemotherapeutic agents, 5-Fluorouracil (5-FU) is a good candidate for encapsulating into the liposomes; however, it has been difficult to obtain liposomal 5-FU with high encapsulation efficiency. The various factors such as preparation method (thin film hydration method and passive loading with small volume incubation method), drug amount (10 mg, 7.5 mg, and 5 mg), hydration volume (3.5 mL and 2 ml), and incubation volume (2 mL and 1 mL) were investigated to optimize the formulation of 5-FU encapsulated liposomes. Liposomes were characterized according to particle size, polydispersity index (PDI), zeta potential, and encapsulation efficiency (EE%). The in vitro release study was carried out using Franz diffusion cell. Based on the optimization of formulation, the average drug EE% and the mean particle size of 5-FU-loaded liposomes were found to be 25% and 188.6 nm. In vitro drug release of 5-FU-loaded liposomes (SVI-4) presented a biphasic release of 5-FU, and this behavior was in accordance with the first-order equation. According to the results, 5-FU can be effectively loaded into liposomes prepared by passive loading with small volume incubation method.