Microcápsula polissacarídica à base de pectina da citrus sinensis contendo extrato oleoso da polpa do euterpe oleracea para o carreamento de paclitaxel

Abstract

Paclitaxel (Taxol®), used against various cancers, causes adverse effects due to its excipient and low aqueous solubility, limiting its administration to the intravenous route (low oral bioavailability). Nanostructured materials are a promising alternative for transporting drugs, improving their dispersion, stability, and efficacy while minimizing the adverse effects associated with conventional formulations. The aim of this research was to synthesize polysaccharide powder microcapsules for the transport of paclitaxel (PTX) using a nanoemulsion prepared with the oily extract of açaí pulp (EOA) and orange pectin (PLJ) as a wall material. To this end, the raw materials were extracted and characterized. Next, an experimental study was conducted that selected nanoemulsions N11A (with PTX) and N11C (control), which subsequently gave rise to the respective microcapsules M11-A and M11-C dried in a spray dryer. The formulations were characterized by Fourier Transform Infrared Absorption Spectroscopy (FT-IR), Differential Scanning Calorimetry (DSC), X-Ray Diffraction (XRD), Scanning Electron Microscopy (SEM) and Transmission Electron Microscopy (TEM). The encapsulation efficiency (EE%) of the formulations was determined using the High-Performance Liquid Chromatography (HPLC) technique. An in vitro release kinetics study was also carried out on M11-A and pure PTX. In vitro cytotoxicity (MTT method) was determined in tumor cell cultures. Non-clinical safety assessment of M11-A and M11-C in zebrafish was performed. DLS analysis of the nanoemulsions and microcapsules redispersed in water showed that the particle sizes ranged from 157 to 220 nm. The FT-IR, DSC and XRD techniques showed the encapsulation of PTX, while the HPLC technique determined an EE% of 99.87 and 83.72% for the N11A and M11-A formulations, respectively. SEM analysis showed that the microcapsules were between 1.12 and 3.06 µm in size. MET analysis of M11-A redispersed in water showed an average particle size of 0.55 ± 0.34 µm. M11-A showed a controlled release profile in vitro, with an accumulated amount of PTX equal to 9.92 ± 0.95% during the 72 h of the experiment, unlike free PTX (31.99 ± 4.79%). M11-A showed greater cytotoxicity than non-encapsulated PTX, with IC50 values of 0.33 (HL-60), 0.98 (HCT-116), and 2.30 (PC-3) ng mL-1, and was not toxic in L-929. In vivo, the formulations did not alter locomotion nor were they toxic to zebrafish. M11-A has shown promise for cancer treatment, with therapeutic potential to minimize the adverse effects of PTX.