Desenvolvimento e caracterização de nanocápsulas poliméricas de policaprolactona contendo 5-fluorouracil empregando planejamento fatorial

Abstract

5-Fluorouracil (5-FU) is one of the drugs used in the chemotherapy of several types of cancer, including colorectal cancer, which is the third type of malignant neoplasm with the highest incidence in the world today. In the treatment with this active principle, there are a series of challenges to be overcome, such as its high toxicity, which leads to several effects after administration, such as myelosuppression, mucositis and diarrhea. In addition, the pharmacokinetics of 5-FU also hinders its response to treatment, since after its metabolization in the body, only about 20% of the initial dose remains. Therefore, there is a need to develop strategies to optimize the use of this drug. One of the ways is the use of nanotechnology to deliver 5-FU, however the encapsulation of this molecule is challenging due to its hydrophilic character. In order to improve the delivery of this drug and reduce its adverse characteristics, polymeric nanocapsules containing poly-Ɛ-caprolactone were used, using a Box-Behnken-type factorial design, a quality by design tool. The methodology used to prepare the nanocapsules was the double emulsification-evaporation of solvent. The variables used in the study were the amount of dichloromethane, concentration of polyvinyl alcohol (PVA) and amount of polycaprolactone (PCL). The formulations were characterized based on hydrodynamic diameter, polydispersion index, zeta potential and encapsulation efficiency. The optimized formulation was prepared with the conditions 9.8mL of dichloromethane, 0.5% PVA and 55.15mg of polycaprolactone, resulting in an average size of 158 nm, polydispersion index 0.085. The encapsulation efficiency reached 29.87% and zeta potential of -20.95 mV. Morphology evaluation by scanning electron microscopy showed spherical nanoparticles. The FTIR technique allowed the identification of the constituents of the nanoparticle. Thus, the present study achieved its main objective, since it was possible to develop and characterize polymeric nanoparticles containing 5- FU, with nanometric size and low polydispersion. However, additional studies will be carried out to increase the 5-FU encapsulation efficiency.