Enhanced Brain Biodistribution of Quercetin and Rutin Co-Loaded Pegylated PLGA Nanoparticles Via Intranasal Delivery for Neuroblastoma Therapy

Abstract

Purpose

Neuroblastoma (NB) is a frequent malignancy in children detected outside the brain with its feature of frequent relapses, poor outcome, and very high toxicity of standard chemotherapy. In order to treat NB, this effort aimed to develop and optimize PLGA-PEG-PLGA nanoparticles loaded with rutin and quercetin for nasal delivery to the brain.

Methods

The nanoparticle formulation was prepared by the method of nanoprecipitation and optimized by Central Composite Design (CCD) with PLGA and stabilizer (Poloxamer 188) concentrations as independent variables. After optimization, the polymeric formulation was assessed using particle dimensions, polydispersity index, zeta kinetic potential, entrapment efficiency (EE), SEM, FTIR, and in vitro drug release studies. The produced formulation’s anticancer efficacy was investigated using the MTT test on neuroblastoma cells, and biodistribution studies in Wistar rats after nasal administration were carried out.

Results

The nanoparticles had a zeta potential of -14.34 mV, with particle sizes varying between 213.7 and 245.8 nm, and an acceptable particle size distribution (0.218–0.258). For quercetin and rutin, the drug loading efficiency was determined to be 80% and 82%, respectively. FTIR analysis also showed that there was no drug-excipient interaction. With a cumulative percentage release of 82.3% from nanoparticles and 68.9% from the plain solution in a 24-hour period, the in vitro drug release research was shown to fit the Hixson-Crowell model. When compared to free drug, nanoparticles had a considerable cytotoxic impact on SH-SY5Y cells, with an IC₅₀ value of 568.1 ± 0.12 µg/ml. When compared to mucoadhesive suspension, the concentration of quercetin and rutin in brain tissue increased by 2.35 and 2.40 times, respectively, in an in vivo investigation of mucoadhesive nanoparticles through intranasal delivery.

Conclusion

The optimized PLGA-PEG-PLGA nanoparticle formulation offers a stable, sustained-release intranasal delivery system for co-administration of quercetin and rutin, with enhanced anticancer cell line efficacy relative to the free drugs, supporting further preclinical evaluation for NB treatment.