Sonwani_2025_Nanomedicine.(Lond)__1

AIM: In the present research work, multifunctional dendrimeric nanoconjugates were developed, where poly(amidoamine) dendrimer generation 4.0 (G4.0) was conjugated with folic acid and N-acetyl cysteine simultaneously to deliver rutin for potential neuroprotective applications. METHODS: G4.0 was functionalized with folic acid and N-acetyl cysteine by carbodiimide coupling chemistry, and the conjugation was confirmed using (1)H NMR and FTIR spectroscopy. Further, rutin was incorporated within the conjugate, and the rutin-loaded dendrimeric conjugate was evaluated for size, drug release, cytotoxicity, cellular uptake, and antioxidant activity. RESULTS: The results of FTIR and (1)H NMR confirmed the conjugation of folic acid and N-acetyl cysteine over the dendrimeric surface. The particle size of NAC-FA-G4.0 was 163.4 +/- 16.63 nm, which was increased to 229.76 +/- 14.05 nm following the rutin incorporation. The in vitro drug release study showed an initial burst release of rutin, i.e. 44.27 +/- 6.4% from dendrimeric conjugate within 4 h, followed by sustained release up to 72 h. The safety and biocompatibility of the developed nanoconjugate were confirmed by the hemolytic toxicity and cytotoxicity studies. CONCLUSION: The developed rutin-loaded dendrimeric conjugate showed improved antioxidant activity and acetylcholinesterase inhibition, suggesting promising neuroprotection properties and hence may be further explored for the treatment of neurodegenerative diseases, including Alzheimer's disease.