Lipossomas contendo 5-fluoruracil : estudo de formulação

Abstract

Colorectal cancer (CRC) is the third most common cancer-related cause of death in men and women. The chemotherapy-based treatment of CRC utilizes 5-Fluorouracil (5-FU) as the main drug, which is a well-established medication for CRC and other cancers. Despite being the first option for metastatic cancer treatment or adjuvant therapy, its use is limited due to rapid metabolism and cytotoxic effects, leading to side effects such as fever, mucositis, stomatitis, nausea, vomiting, diarrhea, leukopenia, neutropenia, thrombocytopenia, and anemia. In this context, nanotechnology has been applied to improve the characteristics of 5-FU and reduce its adverse effects by encapsulating it in nanocarriers such as liposomes, which are vesicles composed of a lipid bilayer surrounding a concentric core. However, 5-FU is a small-sized (130.08 g/mol) and hydrophilic molecule, posing a challenge to encapsulate it within the aqueous core of liposomes. Therefore, this study aims to investigate the effect of composition on the physicochemical characteristics of liposomes containing 5-FU. For this purpose, liposomes were developed with a ratio of 70:30:5 of phospholipid [either soybean phosphatidylcholine (SPC), hydrogenated soybean phosphatidylcholine (HSPC), distearoylphosphatidylcholine (DSPC), or dipalmitoylphosphatidylcholine (DPPC)]:cholesterol:pegylated distearoylphosphatidylethanolamine 2000 (DSPE-PEG2000), using 25 mg or 50 mg of phospholipid as the formulation base. The developed liposomes were characterized for particle size (PS), polydispersity index (PDI), zeta potential (ZP), and encapsulation efficiency (EE%). Among the studied formulations, one was selected for characterization using Fourier-transform infrared spectroscopy (FTIR) and in vitro release profile analysis. The results demonstrated that liposomes based on DSPC exhibited the most favorable physicochemical characteristics. For FTIR characterization and release profile analysis, an HSPC-based liposome was chosen, as a concurrent investigation showed improved encapsulation of 5-FU in the presence of an encapsulated protein. Changes in the infrared (IR) spectrum of HSPC liposomes were observed in the presence of 5-FU, with alterations in bands related to C=O and disappearance of the characteristic C-F band present in the spectrum of 5- FU, suggesting encapsulation of 5-FU. The release profile of HSPC liposomes indicated that 96% of the drug was released within half an hour of the experiment, which may be attributed to a method limitation. Thus, this study successfully developed and characterized liposomes based on different types of phospholipids and observed their effects on PS, PDI, ZP, and EE%, with DSPC liposomes identified as the most efficient for 5-FU encapsulation and DPPC as the least efficient. FTIR analysis suggests the encapsulation of 5-FU in the liposome. Future studies could be conducted to further describe the effect of composition on liposomes using techniques such as atomic force microscopy, differential scanning calorimetry, and X-ray diffraction.