Chitosan-coated nanostructured lipid carriers of amantadine for nose-to-brain delivery: formulation optimization, in vitro-ex vivo characterization, and in vivo anti-parkinsonism assessment.

Amantadine hydrochloride (AMH) is a repurposed moiety of anti-viral category having significant response against Parkinsonism. Nasal route is linked with the direct delivery of drugs to brain through olfactory and trigeminal nerves. The mucociliary clearance is the major obstacle for effective delivery of drugs. The optimized formulation was coated with chitosan (CH) to enhance the residence time of formulation in the nasal cavity. The optimized NLCs exhibited particle size of 174.2 ± 1.5 nm, PDI of 0.131 ± 0.019, zeta potential of -27.52 ± 3.29 mV, EE of 74.06 ± 2.3 %, and nasal flux of 66.03 ± 0.9 μg/cm2/h. FTIR analysis revealed AMH-excipient compatibility and encapsulation of AMH into NLCs. XRD analysis confirmed no polymorphic transition in the developed NLCs. Drug release exhibited sustained release of AMH (71.01 ± 2.19 %) up to 24 h. Ex vivo study (goat nasal mucosa) showed 3.22 folds enhanced permeability of AMH from AMH-NLCs in comparison to AMH-Sol. The recommended storage condition for AMH-NLCs was found to be 25 °C/60 % RH. AMH-NLCs showed high cell viability (88.23 ± 7.49 %) in comparison to AMH-Sol (62.14 ± 6.81 %) on H2O2 induced PC12 cells at a concentration level of 100 μg/ml. In vivo studies exhibited effectiveness of CH-AMH-NLCs and AMH-NLCs and showed increased response when compared with amantadine solution (pure form) and marketed formulation.