Intranasal drug delivery provides rapid absorption and high bioavailability while reducing systemic exposure, making it a hopeful route for nose-to-brain (N2B) transport. However, no effective N2B system has yet been systematically studied for cetrorelix, which is a GnRH antagonist used in reproductive medicine. In this study, a cetrorelix-loaded chitosan-Pluronic F-127 (Chi-Plx) nanoparticle system with a complementary Plx in-situ gel to extend nasal residence time was developed. The formulations were characterized for physicochemical properties, release behavior, cytotoxicity, and pharmacokinetics in rats. Chi-Plx nanoparticles exhibited a mean diameter of 18.7 ± 2.1 nm, PDI of 0.35 ± 0.03, and near-neutral zeta potential. They demonstrated a biphasic release profile with an initial burst (52%) followed by sustained release, achieving 70-80% cumulative release at 1440 min, while the in-situ gel released 65-70% over the same period. Cytotoxicity assays confirmed acceptable biocompatibility, with lower toxicity than the gel formulation. Pharmacokinetic analysis revealed that Chi-Plx nanoparticles achieved markedly higher brain Cmax (223.6 ± 3.6 ng/ml) and drug targeting efficiency (81.8 ± 0.7) compared to the in-situ gel (Cmax 81.6 ng/ml; Drug targeting efficiency (DTE) 34.7) and subcutaneous injection (Cmax 218.2 ng/ml; Drug targeting efficiency (DTE) 1.0). Serum exposure was substantially reduced after intranasal administration, minimizing systemic distribution. This study demonstrates, for the first time, that cetrorelix-loaded Chi-Plx nanoparticles can efficiently deliver peptide drugs to the brain via the intranasal route, offering a promising, needle-free strategy to enhance patient compliance and reduce adverse effects in GnRH-related therapies.
Keywords: Cetrorelix; Chitosan-poloxamer; In-situ gel; Nanoparticles; Nose to brain drug delivery.
© 2026. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.