Orange Trunk Waste-Based Lignin Nanoparticles Encapsulating Curcumin As a Photodynamic Therapy Agent Against Liver Cancer

Orange wood biomass is an interesting lignocellulosic material, but its lignin has been little explored. As a structural macromolecule present in the plant cell wall, lignin has been used in nanoencapsulation and nanomedicine, standing out as a good drug carrier. In this study, lignin was extracted by soda pulping process and used to produce nanoparticles for curcumin encapsulation and subsequent application in photodynamic therapy (PDT). The nanoparticles were synthesized by the solvent shifting process and characterized with UV-vis, fluorescence, dynamic light scattering (DLS), xi-potential, and scanning electron microscopy (SEM). The lignin was soluble in organic solvent and presented an extraction yield of 20.6 +/- 2%. The Fourier transform infrared (FTIR) spectroscopy and NMR signals showed that the lignin presents hardwood-type characteristics. The lignin nanoparticles were easily obtained and presented average sizes of 284 +/- 60, 287 +/- 60, and 502 +/- 100 nm for pure lignin, 1% curcumin, and 5% curcumin nanoparticles, respectively. They exhibited a negative xi-potential of about -42 +/- 5 mV. The formulations were evaluated for 30 days and remained stable in phosphate-buffered saline (PBS). The curcumin encapsulation yields were high, above 90% in all formulations. Scanning electron microscopy (SEM) images showed that the nanoparticles are spherical and homogeneous. Studies using hepatocarcinoma (HTC) and HepaRG cells showed that the lignin nanoparticles were nontoxic within 4 h of incubation, and for nanoparticles containing 5% curcumin, toxicity was observed upon application of light in PDT experiments.