Ref.: MpoBi02-006
Apresentador: Heloísa Bremm Madalosso
Autores (Instituição): Oliveira, J.L.(Universidade Federal de Santa Catarina); Madalosso, H.B.(Universidade Federal de Santa Catarina); Agner, T.(Universidade Federal de Santa Catarina); Cesca, K.(Universidade Federal de Santa Catarina); Sayer, C.(Universidade Federal de Santa Catarina); Immich, A.S.(Universidade Federal de Santa Catarina);
Resumo:
Phototherapy has aroused great interest in the scientific community due to its low invasiveness, toxicity, reduced adsorbed effects and lack of drug resistance in the treatment of cancer. Therapies such as Photodynamic comprise the administration of a photosensitizer (PS) that, when absorbing light at a specific wavelength, produces a cytotoxic response to the tumor tissue, by releasing cytotoxic reactive oxygen species. Despite being a non-invasive technique, there are still clinical limitations in its application due to the low accumulation of the photosensitizer (PS) in the tumor tissue and its short blood circulation time, either due to its deactivation by biomolecules or its low solubility in the environment. These limitations can be overcome by encapsulating the photosensitizer, improving its stability and controlling its photoactivity. This work aims to encapsulate the photosensitizing agent Indocyanine Green (ICG) and the chemotherapy drug Doxorubicin Hydrochloride (DOX) in Poly(Globalide) (PGl) nanoparticles (NPs). PGl was synthesized via Ring Opening Enzymatic Polymerization at 65ºC using Novozym 435, immobilized Candida antarctica B lipase (Cal-B), as biocatalyst. Nanoparticles coencapsulating ICG and DOX were prepared by the Double Emulsion by Solvent Evaporation technique and were analyzed for hydrodynamic particle size and polydispersity index (PDI) by Dynamic Light Scattering (DLS). PGl and NPs were characterized regarding their chemical structure, thermal properties and molecular weight. The encapsulation efficiency (EE%) of ICG and DOX was determined by Ultraviolet-visible Spectroscopy and Fluorescence, respectively. Different formulations and experimental conditions were evaluated, and under optimized conditions, NPs with less than 300 nm and PDI < 0.2 were obtained. TEM images revealed the spherical shape of the nanoparticles and corroborated the submicrometer sizes determined by DLS. The EE% of ICG in PGL NPs, for the 4 formulations (in triplicate) were greater than 83.2 ± 0.4% and 59.5 ± 2.2% for DOX. Thus, the double emulsion technique proved to be an efficient strategy to encapsulate ICG and DOX, singly (ICG) or doubly loaded in PGl NPs. Corroborating the literature, there was an increase of approximately 8.5% in the EE% of ICG when added to DOX in the formulation of NPs. A 6-month study was conducted and the NPs demonstrated stability, maintaining their hydrodynamic size and pH. For the cytotoxicity study on L929 fibroblast cells, concentrations of NPs below 168.7 ng mL-1 were not cytotoxic after 24 h of incubation, with cell viability above 70%. In tests on cells of the SKMEL-28 tumor lineage, using an 808 nm laser, the irradiation time was a determining factor in photodynamic/photothermal therapy, irradiation during 10 min produced the best results, with metabolic activity between 70% and 80%. This study highlighted the potential of these nanoparticles in phototherapy.