Desenvolvimento e avaliação in vitro de lipossomas contendo 5-fluorouracil e R-ficoeritrina no tratamento do câncer colorretal

Abstract

The 5-Fluouracil (5-FU) is the first-rate drug for the treatment of colorectal cancer (CCR), which is considered the 3rd type of cancer most prevalent to the world. R - phycoerythrin (R-PE) is an isolated ficobiliprotein of red algae as Solieria filiformis, with fluorescent property, which makes it possible to this protein in photodynamic therapy (PDT), and have potential for cancer treatment. Liposomes are nanocarrers capable of encapsulating hydrophilic molecules, such as 5-FU and R-PE in the aqueous nucleus, which can be used to improve the effectiveness of cancer treatment, for example, for the permeability effect and increased retention (EPR). Thus, the present work aimed to develop 5-FU and R-PE coelopsulated liposomes to for the treatment for CCR. From this perspective, it was defined which composition of liposome, developed by the lipid film hydration method, would be ideal for this nanosystem, being evaluated the lipids: soybean phosphatidilcoline (SPC); diesteroilfosphathydilcholine (DSPC); Dipalmitoilophosphatidilcoline (DPPC) and hydrogenated soy phosphatidilcoline (HSPC). The results of the liposomes showed what contained the HSPC lipid in the amount of 50mg performed better, as the result of polydispersion index (PDI) was 0.100 ± 0.022. In addition, in this composition the particle size and zeta potential were respectively 103.43 ± 1.31 and -12.23 ± 0.35. The encapsulation efficiency results (EE%) were 94 ± 2.357%, for R-PE, and 42 ± 2.767%, for 5-FU. In the morphological evaluation it was possible to observe the spherical structure of liposome. Regarding the stability study, liposomes maintained the particle size, PDI and potential zeta values in a stable range. In cell viability assessment studies in the HCT-116 CCR lineage the IC50 value for R-PE and 5-FU concentration, in coencapsulated liposomes, was respectively 10.010 μm and 0.020 μm, in cytotoxicity, and 8.836 μm and 0.017 μm, in phototoxicity, with absent synergism. Therefore, the HSPC 50 formulation, co-encapsulated with R-PE and 5-FU, is a promising alternative for a for the treatment for CCR. Furthermore, dose adjustments of the molecules, as well as the time of exposure to light, can be made to better understand and use this formulation as a photosensitizer.