Precision Nano-Engineering of Curcumin for Diabetic Nephropathy: Mechanistic Targeting, AI-Guided Optimisation, and Translational Barriers.

Abstract

Despite advances in glucose-lowering therapies, DN remains one of the leading causes of end-stage renal disease (ESRD), thereby underscoring the necessity of an efficacious multi-target approach. Recent data strongly indicate that renal metabolic dysregulation plays a central role in kidney injury, which in turn causes redox imbalance, inflammatory reaction, damaged mitochondria, ferroptosis, and renal scarring. Multi-target therapeutic strategies (MTTS) encompass either a single drug with multiple actions or a combination of drugs targeting different biological pathways. Curcumin, a natural polyphenol, modulates oxidative stress, inflammation, and fibrotic signalling andis well suited to a multi-target therapeutic strategy. However, its clinical use is limited by poor aqueous solubility, rapid metabolism, low oral bioavailability, and consequently limited systemic and renal exposure. Nanotechnology- based drug delivery systems, including polymeric nanoparticles and lipid-based carriers, have been investigated to overcome these pharmacokinetic limitations; however, enhanced renal exposure requires standardised pharmacokinetic and tissue-distribution evidence.

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