Nanopartículas magnéticas e lipídicas para liberação direcionada de quercetina no câncer de cólon

Abstract

Drug delivery systems based on nanoparticles can improve pharmacokinetic aspects such as controlled release and release from passive and active drug targeting, increasing therapeutic efficacy and reducing toxicity in conventional colon cancer treatment. The superparamagnetism of magnetic nanoparticles (MNP) appears to be a potential alternative for magnetothermal therapy, inducing tumor cell death by hyperthermia with the ability to control and target by an external magnetic field. Solid lipid nanoparticles (SLN) are effective carriers of lipophilic anticancer agents such as quercetin (QC). The polymer functionalization technique improves the stability and targeting of nanoparticles; thus, this study aimed to develop MNP and SLN coated with chitosan and chitosan conjugated to folic acid (FA-CS) for QC release. After synthesizing FA-CS and selecting the optimum functionalization methods, a 3^2 factorial design was conducted to identify and optimize the parameters influencing the development of MNP and SLN. The systems were characterized using scanning microscopy, dynamic light scattering, Zeta potential, as well as validated UV-vis spectrophotometry and high-performance liquid chromatography methods to quantify encapsulation efficiency and drug loading. FA-CS was characterized, confirming the interaction between the functional groups (R-NH2 and R-COOH) with a 72.92%

efficiency. The functionalization method by shaker and magnetic separation of MNP- CS (FM3) and in situ functionalization of SLN-CS by sonicator (FL3) produced particles

with sizes of 483.57 nm (PDI 0.49) and 508.45 nm (PDI 0.53), respectively, with a zeta of 29.97 mV and 9.51 mV. Following the factorial design, it was discovered that the MNPs' Zeta potential is positively influenced by the CS concentration, followed by the CS-temperature interaction, which has statistical relevance. To optimize the highest Zeta potential response and minimal mean diameter (d = 1), a formulation with 2 mg.mL-1 of CS produced at 30oC was used. The SLN, on the other hand, was chosen as the formulation with the highest optimum response of Zeta potential, EE, and content and the lowest mean diameter and PDI, using 1 mg.mL-1 of CS and 10 minutes of sonication. The optimized formulations had diameters of 122.32 nm (SD ± 8.56) and 352.83 nm (SD ± 62.8), PDI of 0.46 (SD ± 0.05) and 0.23 (SD ± 0.17), and Zeta potentials of +30.78 mV (SD ± 0.8) and +14.2 mV (SD ± 5.9) for MNP and SLN,

respectively. The EE values obtained were 80.45% (MNP-CS-QC), 54.4% (MNP- FACS-QC), 69.73% (SLN-QC-CS), and 83.82% (SLN-QC-FACS). The dissolution

assay demonstrated release control for MNP-CS-QC (up to 6.4% in 24 hours) and burst release for SLN-QC-CS (up to 77.2% in 1 hour), with minimal difference between non-conjugated and conjugated polymers. According to the findings of this study, the experimental design allowed for the discussion of critical variables in the manufacture of these nanoparticles, as well as the determination of the optimal parameters for the formulations of MNPs and SLNs functionalized with chitosan and chitosan-folate. Further research is needed, but this study aims to contribute to developments in biomedical nanotechnology and the debate of magnetic and lipid systems by highlighting the potential of quercetin nanoparticles.