20.500.12556/RUL-175590 Delivery strategies to improve the pharmacological efficacy of NRF2 modulators a review The NRF2/KEAP1 signaling pathway regulates the gene expression of numerous cytoprotective and detoxifying enzymes and is therefore essential for maintaining cellular redox homeostasis. Despite the increasing knowledge of NRF2 signaling complexity, dimethyl fumarate remains the sole NRF2-targeting therapy in clinical practice, used for multiple sclerosis. Ongoing research exploring the role of NRF2 in cancer, neurodegeneration, diabetes, and cardiovascular, renal, and liver diseases holds significant promise for future therapeutic innovation. The therapeutic potential of NRF2 modulators, while supported by positive research and clinical data, is often restricted due to factors including low solubility, poor stability, poor pharmacokinetic parameters, and a lack of specificity that results in off-target effects. Therefore, designing an effective pharmaceutical formulation is one of the significant barriers to their clinical translation. This article addresses these challenges by reviewing various drug delivery strategies with a particular emphasis on polymeric nanoparticles, liposomes, polymeric micelles, carbon nanotubes, micro/nano-emulsions, and biomimetic nanoparticles. The potential of these systems to enhance the pharmacological activities of NRF2 modulators—driven by their small particle size and customizable properties—is discussed on a disease-by-disease basis, focusing on cancer, neurodegenerative, and inflammatory diseases. While these systems have shown considerable success in preclinical studies, their clinical application is constrained by hurdles in safety, scalability, stability and regulatory compliance. This transition has not yet been achieved for NRF2 modulators, but intensive research is ongoing. Therefore, the overall aim of this article is to provide a comprehensive understanding of delivery strategies for NRF2 modulators, ultimately guiding the development of more effective therapies and improving their clinical applications. Nrf2 modulators nanomedicine nanomedicine-Nrf2 modulator synergy the therapeutic potential of NRF2 modulators chemopreventive agents cancer therapeutics neurological therapeutics oxidative stress signaling pathway modulatorji Nrf2 nanomedicina sinergija med nanomedicino in modulatorjem Nrf2 terapevtski potencial modulatorjev NRF2 kemopreventivna sredstva zdravila za zdravljenje raka nevrološka zdravila oksidativni stres signalna pot true false true Angleški jezik Slovenski jezik Članek v reviji 2025-11-05 09:19:12 2025-11-05 09:19:19 2025-12-12 03:55:25 0000-00-00 00:00:00 2025 0 0 Str. 4599-4616 iss. 10 Vol. 16 Aug. 2025 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 615.4:54:575.117 2632-8682 10.1039/D5MD00571J 254941443 d5md00571j.pdf d5md00571j.pdf 1 DE52417E4BC8161339320A216EC88213 e19088b0c8a03736d7b1fcdc6f80533684bae14557ed0f1d6ad52c4091042a18 fc8067ed-bbad-11f0-9328-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=221620 https://pubs.rsc.org/en/content/articlelanding/2025/md/d5md00571j 1 d4a4302b-ba1f-11f0-9328-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=221363 Fakulteta za farmacijo 0 0 0