Development of lignin-based nanoparticles using green chemistry for targeted delivery of doxorubicin to breast cancer cells: In-silico and in-vitro study.

The development of nanostructure-based drug delivery systems continues to advance in cancer therapy, but most reported approaches still rely on metal or synthetic-based materials that may have limitations in terms of biocompatibility and environmental sustainability. The use of emulsion-based systems as eco-friendly nanostructure platforms remains relatively underexplored. A doxorubicin (DOX) delivery system was developed based on nanolignin isolated from oil palm empty fruit bunches (OPEFB) using a green Deep Eutectic Solvent (DES). The obtained lignin was converted into nanolignin via ultrasonication and formulated into a nanoemulsion system containing Tween 80, ethyl propionate, and DOX. The resulting nanoemulsion system showed nanometer-scale particle size, high encapsulation efficiency, and good physical stability. The drug release test showed pH-responsive release behavior, where the DOX release rate increased in acidic conditions (pH 6.4), simulating the tumor microenvironment. The DOX release mechanism in the tumor microenvironment was explained by the Korsmeyer-Peppas model, which showed that DOX release into this cancer cell environment follows quasi-Fickian diffusion. In the MTT assay using MCF-7 cells, the Lignin-Enriched formulation was notable, showing the strongest cytotoxicity. DFT experiments supported these findings, revealing that the Lignin-Enriched system possesses higher binding energy, signifying stronger molecular interactions. Additionally, the Green Star Area Index (GSAI) further validated the process, confirming that it aligns with green chemistry principles. Thus, these findings indicate that the developed emulsion-based drug delivery system offers a promising, effective, and environmentally friendly platform for biomedical applications, particularly as a green alternative to conventional drug delivery systems.