Development and Characterization of Bromocriptine Mesylate loaded Nanostructured Lipid Carriers for Enhanced nose-to-brain delivery

Bromocriptine Mesylate is an alkaloid ergot derivative that acts as a dopamine D2 agonist. The work aims to develop nanostructured lipid carriers (NLCs) of bromocriptine mesylate to improve its bioavailability, which is only 28% orally. The nasal route is one of the best methods to deliver drugs directly to the brain. To increase brain uptake through the direct nose-to-brain channel, bromocriptine mesylate-loaded nanostructured lipid carriers (BCM-NLCs) were prepared and assessed for the application. The formulations were prepared based on 32 full-factorial experimental designs to study the effect of the formulation variables, such as total lipid ratio and concentration of surfactants. BCM-NLCs were prepared using the ultrasonic dispersion method, and processing parameters such as total lipid ratio and concentration of surfactants were optimized, then characterized. The BCM-NLCs were analyzed in rats for comparative drug release studies via oral and intranasal routes. The optimized BCM-NLCs showed a mean particle size of 108.4±0.26 nm, a polydispersity index of 0.344, zeta potentials of -42.8±0.52 mV, entrapment efficacy of 91.1±0.04 %, and drug content of 99.9%. The in vitro studies revealed that bromocriptine was released from NLCs in two phases: an initial burst followed by a steady release for 24 hours. The Korsmeyer-Peppas (0.9147) model is suitable for release kinetics. In-vivo studies showed that the concentration of optimized BCM-NLCs increased when administered via the intranasal route (C~max=703.05±2.21µg/ml; t~max=12hr) compared to the oral (C~max=231.16±1.13µg/ml; t~max=12hr) approach. The BCM-NLCs remained stable at 4-8±2°C for three months. We concluded that bromocriptine mesylate-loaded nanostructured lipid carriers could be potentially used as intranasal drug delivery carriers to manage Parkinson’s disease.