Journal
NEUROPHARMACOLOGY
Volume 201, Issue -, Pages -Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuropharm.2021.108832
Keywords
Nose to brain delivery; Lecithin-chitosan nanoparticles; Piribedil; Intranasal pharmacokinetic studies; Brain distribution studies; Design of experiments
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By developing lecithin-chitosan hybrid nanoparticles, the direct nose to brain uptake of Piribedil for Parkinson's disease treatment was improved, resulting in increased bioavailability in the brain. The development of this novel nanoformulation effectively addressed drug delivery issues present in traditional administration methods.
Piribedil (PBD) is a compound that has shown efficacy in clinical trials to treat motor and non-motor symptoms of Parkinson's disease. However, drug delivery issues like low oral bioavailability, high dosing frequency (3-5 tablets/day), gastrointestinal side-effects reduced the clinical use of PBD. In this work, we have developed lecithin-chitosan hybrid nanoparticles (PBD-LCNs) to improve the direct nose to brain uptake of PBD. PBD-LCNs were optimized using hybrid design approach based on DoE. The mean particle size and drug loading of PBD-LCNs were 147 nm, and 12%, respectively. The PBD-LCNs showed good stability and were found to be nearly spherical in shape. Further, the optimized LCNs were loaded in methylcellulose thermo-responsive in situ gel (PBD-LCN-ISG) to overcome rapid mucociliary clearance upon intranasal administration. Plasma and brain pharmacokinetic studies in rats showed that PBD-LCN-ISG increased the relative bioavailability of PBD in brain (AUCbrain) by about 6.4-folds and reduced the (Cmax)plasma by 3.7-folds when compared to plain intranasal suspension of PBD (PBD-Susp). Further, PBD-Susp showed limited direct nose to brain uptake with DTP values less than 0, while the optimized PBD-LCNs showed DTP value of 56% indicating efficient direct nose to brain uptake. Overall, the development of nanoformulations significantly improved the direct nose to brain uptake of PBD.
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