Development of a Eudragit-Chitosan Nanosystem for the pH-Dependent Transport of Duloxetine to the Brain: Synthesis, Characterization and In Silico Modeling Analysis

The purpose of this study was to synthesize duloxetine (DLX)- loaded Eudragit-Chitosan (Eud-CHT) nanoparticles enclosed in an oral gelatin capsule and to evaluate the potential to transport DLX to the blood-brain barrier (BBB)for improved neuro-availability. The utilization of Eudragit® with chitosan offers a pH-dependent controlled drug release. The physicochemical properties of the formulated DLX-loaded Eud-CHT nanosystem were confirmed using various characterization techniques. SEM confirmed the nanoparticle morphology and pore size distribution. The particle size was 100 ± 73,41 nm, with a polydispersity index (PDI) of 0,283 and zeta potential of 16±2,79 mV. Drug entrapment efficacy (DEE) of 72% was attained, and molecular modelling predicted an efficient and controllable drug delivery system. The release of DLX from the nanosystem was evaluated at pH1.2, pH 6.8 and pH 7.4. At a pH of 6.8, 40 % of DLX was released, with only 20 % at pH 1.2 and 35% at pH 7.4. This demonstrated DLX's pH-dependent release and the Eud-CHT nanosystem's shielding effect at gastric pH.  In addition, HEK 293 neural cells confirmed the non-toxicity of the DLX-Eud-CHT nanosystem. In silico modelling revealed a DLX-Eud-CHT composite with an outer cationic surface attributable to the EUD moieties on nanoparticles for preferential cell recognition and uptake at the anionic cell interface. The combined trials and results from the synthesis of DLX-Eud-CHT nanoparticles showed that these nanoparticles could be utilized as a potentially invaluable formulation for oral drug delivery of duloxetine with improved neuro-availability.