Formulation and Evaluation of Eudragit RL-100 Nanoparticles Loaded In-Situ Forming Gel for Intranasal Delivery of Rivastigmin

Rivastigmine hydrogen tartrate (RHT) is commonly used for the treatment of mild to moderate Alzheimer’s disease (AD). The aim of this work was to formulate in-situ pluronic F-127 (PF-127) hydrogels containing Eudragit RL-100 (EU-RL) nanoparticles (NPs) in order to improve the therapeutic efficacy of RHT through the nasal route.

The NPs were prepared using different polymer to drug ratios and evaluated for their physicochemical characteristics, cellular uptake and in vitro cytotoxicity against lung adenocarcinoma cells (A459). PF-127 nanoformulations were prepared via cold method and analyzed in terms of physicochemical properties and drug release profiles. The nanoformulations and plain drug gel were then assessed by ex vivo permeation studies across the sheep nasal mucosa.

The EU-RL NPs exhibited a particle size within the range of 118 to 154 nm and positive zeta potential values of 22.5 to 30 mV with an approximately spherical shape. Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and X-ray powder diffraction (XRPD) suggested no drug to polymer interaction through the preparation of nanoformulations. The RHT-loaded NPs exhibited an acceptable cytocompatibility with a time- and dose-dependent cellular internalization.

Our results clearly indicated the potential of nanoformulations as controlled release systems to improve the therapeutic efficacy of RHT through the intranasal administration.