Qbd-Engineered Brain-Targeted Mucoadhesive Lipid Nanocarriers of Rutin: In Vitro and In Vivo Evaluation

Introduction: Rutin, a glycoside flavonoid that has high neuroprotective efficacy in neurodegenerative diseases, is hindered by low aqueous solubility and poor oral bioavailability. The major challenge in routine delivery is across the blood brain barrier (BBB). So to resolve these problems, in present study we formulate mucoadhesive nano lipid carrier (MNLCs) for intra-nasal administration for the purpose of enhancing residence time in the nasal cavity and targeting in the brain by utilizing trigeminal and olfactory neuronal routes, thus avoiding the BBB. Methodology: MNLCs were prepared by melt emulsification and probe sonication technique and various formulation parameters such as lipid content, surfactant concentration and sonication time were optimized using quality by design (QbD). Results: Box-Behnken design based on particle size, entrapment efficiency and drug release was utilized. Optimized nano-carriers were coated with -cyclodextrin for imparting mucoadhesive properties. Result: The characteristics of nanocarriers showed that the optimized MNLCs have particle size of 150.8 42.5 nm, polydispersity index of 0.592 and zeta potential of -18.2 mV. In vitro release profile demonstrated a sustained release with 80% drug release over 48 h. SEM demonstrated the presence of-cyclodextrin coating on the surface of the nanocarrier. The in vivo studies revealed increased brain delivery and therapeutic effect through nasal administration. Conclusion: All the results indicate that the cyclodextrin coated MNLCs were successful in the delivery of rutin to brain by intra-nasal administration and have shown a sustained release profile with improved bioavailability and neuroprotection.