PEGYLATED PLGA NANOPARTICLES OF METFORMIN AND CURCUMIN: A PROMISING NANOTHERAPEUTIC APPROACH FOR DIABETIC NEPHROPATHY

Prajval A. Kothale*, Somesh P. Chavan, Dr. Poonm N. Chougule, Dr. Chandraprabhu M. Jangme

Diabetic kidney disease (DN) is a common complication of diabetes and a leading cause of chronic kidney disease worldwide. Long-term high blood sugar causes oxidative stress, inflammation, and scarring in the kidneys, which can lead to protein in the urine (albuminuria) and reduced kidney function.[1] Current treatments can slow diabetic kidney disease but cannot fully stop it, highlighting the need for new therapeutic approaches. Metformin, a first-choice diabetes drug, also protects the kidneys beyond lowering blood sugar. It activates AMPK, improves mitochondrial function, and reduces scarring and damage to kidney tubules.[2] Curcumin, a natural compound from turmeric (Curcuma longa), acts as an antioxidant and anti-inflammatory agent by blocking NF-κB signaling and activating the Nrf2/HO-1 protective pathways.[3] However, both drugs have low bioavailability and do not easily reach the kidneys. Recent studies show that nanoparticles can overcome these problems. PLGA nanoparticles coated with PEG are more stable, stay longer in the bloodstream, and can accumulate in the kidneys more effectively.[4] PLGA nanoparticles carrying metformin release the drug slowly over time and improve its absorption and circulation in the body.[5], PLGA nanoparticles carrying curcumin reduced cell death and scarring in kidney disease models of diabetes.[6] Co-delivery of metformin and curcumin in PEGylated PLGA nanoparticles has been suggested to produce synergistic effects by simultaneously modulating AMPK and Nrf2 pathways.[7] Future prospects include optimization of nanoparticle size and surface ligands for proximal tubule targeting, microfluidic scale-up for reproducible production, and comparative studies with standard DN therapies such as SGLT2 inhibitors and RAAS blockers. Preclinical evaluation and following clinical translation will be critical steps toward establishing PEGylated PLGA-based co-delivery of metformin and curcumin as a promising therapeutic option for DN.[8]