Optimization of Eudragit RS100 Nanocapsule Formulation for Encapsulating Perillyl Alcohol and Temozolomide Using Design of Experiments

Glioblastoma, an aggressive intracranial tumor, presents significant therapeutic challenges due to the restrictive nature of the blood-brain barrier (BBB), which limits the effectiveness of conventional treatments. This study aimed to develop and optimize a nanoencapsulated system for intranasal delivery of temozolomide (TMZ) and perillyl alcohol (POH), designed to circumvent BBB limitations, utilizing Eudragit RS100 as the encapsulation matrix. A factorial design approach optimized key parameters, including Eudragit RS100 concentration, POH amount, drip rate, and organic-to-aqueous phase ratio. The nanocapsules were characterized by dynamic light scattering, zeta potential analysis, scanning electron microscopy, and high-performance liquid chromatography. The optimized nanocapsules demonstrated a mean diameter of 253 ± 52 nm and a polydispersity index of 0.145 ± 0.037, indicating uniform size distribution. A zeta potential of approximately +20 mV supported colloidal stability. Encapsulation efficiencies were 3.7% for POH and 28.5% for TMZ. This nanoencapsulated delivery system offers a promising approach for glioblastoma treatment, potentially enhancing clinical outcomes and reducing treatment-associated toxicity.