Nanopartículas à base de quitosana e polietilenoglicol para encapsulamento do 5-fluorouracil

Abstract

Cancer is becoming a serious threat to public health. Among non-communicable diseases, it is the most prevalent worldwide. Conventional cancer treatments include chemotherapy, radiotherapy, and, in more severe cases, surgery. Among the chemotherapeutic agents used, 5-fluorouracil is widely used in various types of cancer (colon, stomach, and others). However, it presents some problems, including a very short half-life, low bioavailability, and multiple side effects, including liver and kidney damage. Nanoencapsulation is an alternative to overcome these challenges. Nanoparticles (NPs) have excellent characteristics for controlled drug release applications. They can be prepared using a variety of techniques, with ionotropic gelation being one of the most widely used. This combines oppositely charged polymers, with one of them acting as a cross-linking agent. Chitosan (CH) is a naturally occurring, positively charged polysaccharide extensively used in drug delivery systems. Tripolyphosphate (TPP) can be used as a crosslinking agent to produce nanoparticles. Polyethylene glycol is a synthetic polymer that provides longer intravenous circulation time, better diffusion of NPs in tissue, and prevents interactions with other blood components, increasing the bioavailability of the encapsulated material. In this study, eight nanoparticle systems were developed: four without 5-FU and four with 5-FU. The systems showed encapsulation efficiencies ranging from 9% to 28% and carrying capacities of 8.4% to 12.2%. The FTIR spectra of the systems displayed all the characteristic bands of the starting materials. The diameter of the nanoparticles without 5-FU ranged from 146 nm to 303 nm, and with 5-FU, it ranged from 187 nm to 396 nm. The release presented burst release, releasing approximately 55% within 48 hours of the assay, with release kinetics consistent with the diffusion mechanism model. Scanning electron microscopy revealed that the nanoparticles had a spherical morphology. The PEG-containing systems did not exhibit significant interaction with the protein, suggesting a possible longer circulation time for intravenous administration. Cell viability, however, showed that encapsulated 5-FU was more effective against the HCT-116 cell line, with the systems CH/TPP/PEG14505-FU and CH/TPP/PEG3350/5-FU being the most effective in the evaluations performed. The system CH/TPP/PEG1450/5-FU also demonstrated the emergence of encapsulated 5-FU against the MDA-MB-231 cell line, demonstrating great potential for anticancer applications.